An immunohistochemical panel consisting of EZH2, C-KIT, and CD205 is useful for distinguishing thymic squamous cell carcinoma from type B3 thymoma

Publication date: Available online 24 February 2018
Source:Pathology - Research and Practice
Author(s): Bo-Sung Kim, Jin Kuk Kim, Chang Hyun Kang, Young Tae Kim, Kyeong Cheon Jung, Jae-Kyung Won
Type B3 thymoma and thymic squamous cell carcinoma (SqCC) often cause a diagnostic problem due to their histological similarities. The aim of this study is to identify EZH2 as a novel and powerful biomarker that can effectively distinguish thymic SqCC from type B3 thymoma, and find optimal combinations among 11 markers. A total of 53 patients, comprising 26 with type B3 thymoma and 27 with thymic SqCC, were allocated to the discovery or validation cohorts, and immunohistochemical staining was performed and analyzed. The expression level of each marker was scored, and receiver-operator characteristic curve analysis was performed to evaluate their diagnostic accuracies. This analysis identified EZH2, C-KIT, and CD205 as useful markers for distinguishing thymic SqCC, and a combined panel approach using them further improved diagnostic accuracy in both the discovery and validation cohorts. In the combined cohorts analysis, EZH2 was the single best marker with 88.9% sensitivity and 100% specificity [area under the curve (AUC) = 0.967]. The sensitivity and specificity were 85.2% and 100% (AUC = 0.962) for C-KIT, and 100% and 73.1% (AUC = 0.844) for CD205. The combined panel had the highest sensitivity and specificity at 96.3% and 100%, which was significantly or marginally higher than those of EZH2, C-KIT, and CD205 alone (P = 0.071, 0.034, and 0.005, respectively). The present findings indicate that EZH2 is useful as a novel diagnostic marker for distinguishing thymic SqCC and that the panel approach can be used as an effective differential diagnostic tool in daily practice.



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Higher than reported adolescent and young adult clinical trial enrollment during the “Golden Age” of melanoma clinical trials

Abstract

Clinical trial enrollments in adolescents and young adults (AYA) with cancer have historically been lower than those in pediatric and older adult populations. We sought to examine therapeutic trial enrollment rates at our cancer center. We performed a retrospective evaluation of AYA patients treated before and after the first checkpoint inhibitor trial opened at our cancer center in 2007. We examined gender, stage at presentation and insurance status in terms of trial enrollment. We compared the trial participation rate of AYA patients with that of older adults. In this adult facility, 12.7% (1,831) of total patients were between age 15 and 39. Overall therapeutic clinical trial rate was 17.6% which increased to 19.8% since 2007. Both nodal disease or metastatic disease at presentation was associated with increasing odds of trial enrollment (OR = 5.36 and P < 0.001 for nodal disease and OR = 7.96 and P < 0.001 for metastatic disease). There was a nonstatistically significant trend toward improved 3-year overall survival in the AYA patients with advanced presentation that enrolled on clinical trials compared with those not enrolled on trials since 2007. AYA clinical trial enrollment at a comprehensive care center melanoma program was higher than reported in the literature overall for AYA patients. This 1,831 patient cohort may provide a foundation for more detailed investigation toward quantifying the effects of clinical trial enrollment in terms of age-specific benefits and toxicities for AYA patients with malignancies that have their peak incidence in older adults.

Adolescents and young adult (AYA) patients have had lower clinical trial accruals over the past few decades and this has led to fewer survival benefits when comparing these patients to children and older adults with cancer. Here we report nearly 1 out of 5 AYA melanoma patients enrolled on trials during the past decade when these trials improved survival substantially.

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Tinnitus and Self-Harm Revisited

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Speech Understanding and Sound Source Localization by Cochlear Implant Listeners Using a Pinna-Effect Imitating Microphone and an Adaptive Beamformer

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An Argument for Self-Report as a Reference Standard in Audiology

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Test‐Retest Reliability and Minimal Detectable Change of Randomized Dichotic Digits in Learning-Disabled Children: Implications for Dichotic Listening Training

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Description, Normative Data, and Utility of the Hearing Aid Skills and Knowledge Test

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Investigation of Extended Bandwidth Hearing Aid Amplification on Speech Intelligibility and Sound Quality in Adults with Mild-to-Moderate Hearing Loss

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Thoughts about Suicide and Self-Harm in Patients with Tinnitus and Hyperacusis

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Response to Drs. Iliadou and Eleftheriadis Regarding “Auditory Processing Disorder (APD) as the Sole Manifestation of a Cerebellopontine and Internal Auditory Canal Lesion”

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Response to the Letter from Dr. Vermiglio Regarding Iliadou and Eleftheriadis (2017): CAPD is Classified in ICD-10 as H93.25

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JAAA CEU Program

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Editorial Board

Publication date: March 2018
Source:Sleep Medicine, Volume 43





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Long-term prediction of adherence to continuous positive air pressure therapy for the treatment of moderate/severe obstructive sleep apnea syndrome

Publication date: March 2018
Source:Sleep Medicine, Volume 43
Author(s): Francesco Baratta, Daniele Pastori, Tommaso Bucci, Mario Fabiani, Valerio Fabiani, Marco Brunori, Lorenzo Loffredo, Rossella Lillo, Gaetano Pannitteri, Francesco Angelico, Maria Del Ben
BackgroundContinuous positive airway pressure (CPAP) therapy is a highly effective treatment for obstructive sleep apnea syndrome (OSAS). However, poor adherence is a limiting factor, and a significant proportion of patients are unable to tolerate CPAP. The aim of this study was to determine predictors of long-term non-compliance with CPAP.MethodsCPAP treatment was prescribed to all consecutive patients with moderate or severe OSAS (AHI ≥15 events/h) (n = 295) who underwent a full-night CPAP titration study at home between February 1, 2002 and December 1, 2016. Adherence was defined as CPAP use for at least 4 h per night and five days per week. Subjects had periodical follow-up visits including clinical and biochemical evaluation and assessment of adherence to CPAP.ResultsMedian follow-up observation was 74.8 (24.2/110.9) months. The percentage of OSAS patients adhering to CPAP was 41.4% (42.3% in males and 37.0% in females), and prevalence was significantly higher in severe OSAS than in moderate (51.8% vs. 22.1%; p < 0.001; respectively). At multivariate analysis, lower severity of OSAS (HR = 0.66; CI 95 0.46–0.94) p < 0.023), cigarette smoking (HR = 1.72; CI 95 1.13–2.61); p = 0.011), and previous cardiovascular events (HR = 1.95; CI 95 1.03–3.70; p = 0.04) were the only independent predictors of long-term non-adherence to CPAP after controlling for age, gender, and metabolic syndrome.ConclusionsIn our cohort of patients with moderate/severe OSAS who were prescribed CPAP therapy, long-term compliance to treatment was present in less than half of the patients. Adherence was positively associated with OSAS severity and negatively associated with cigarette smoking and previous cardiovascular events at baseline.



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Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal

Publication date: Available online 24 February 2018
Source:Brain Stimulation
Author(s): Logan T. Dowdle, Truman R. Brown, Mark S. George, Colleen A. Hanlon
BackgroundIn the 20 years since our group established the feasibility of performing interleaved TMS/fMRI, no studies have reported direct comparisons of active prefrontal stimulation with a matched sham. Thus, for all studies there is concern about what is truly the TMS effect on cortical neurons.ObjectiveAfter developing a sham control for use within the MRI scanner, we used fMRI to test the hypothesis of greater regional BOLD responses for active versus control stimulation.MethodsWe delivered 4 runs of interleaved TMS/fMRI with a limited field of view (16 slices, centered at AC-PC) to the left DLPFC (2 active, 2 control; counterbalanced) of 20 healthy individuals (F3; 20 pulses/run, interpulse interval:10–15sec, TR:1sec). In the control condition, 3 cm of foam was placed between the TMS coil and the scalp. This ensured magnetic field decay, but preserved the sensory aspects of each pulse (empirically evaluated in a subset of 10 individuals).ResultsBOLD increases in the cingulate, thalamus, insulae, and middle frontal gyri (p < 0.05, FWE corrected) were found during both active and control stimulation. However, relative to control, active stimulation caused elevated BOLD signal in the anterior cingulate, caudate and thalamus. No significant difference was found in auditory regions.Conclusion(s)This TMS/fMRI study evaluated a control condition that preserved many of the sensory features of TMS while reducing magnetic field entry. These findings support a relationship between single pulses of TMS and activity in anatomically connected regions, but also underscore the importance of using a sham condition in future TMS/fMRI studies.



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Combining cognitive training and multi-site rTMS to improve cognitive functions in Alzheimer's disease

Publication date: Available online 24 February 2018
Source:Brain Stimulation
Author(s): Jean-Paul Nguyen, Alcira Suarez, Estelle Le Saout, Michel Meignier, Julien Nizard, Jean-Pascal Lefaucheur




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Short-term quality of life after subthalamic stimulation depends on non-motor symptoms in Parkinson's disease

Publication date: Available online 24 February 2018
Source:Brain Stimulation
Author(s): Haidar Salimi Dafsari, Luisa Weiß, Monty Silverdale, Alexandra Rizos, Prashanth Reddy, Keyoumars Ashkan, Julian Evans, Paul Reker, Jan Niklas Petry-Schmelzer, Michael Samuel, Veerle Visser-Vandewalle, Angelo Antonini, Pablo Martinez-Martin, K. Ray-Chaudhuri, Lars Timmermann
BackgroundSubthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome.HypothesisWe hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome.MethodsIn this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and –activities of daily living, levodopa equivalent daily dose. We dichotomized patients into "QoL responders"/"non-responders" and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned "responders/non-responders" as dependent variable.ResultsAll outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as "QoL non-responders". Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome.ConclusionsOur results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS.



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Neuropeptide Y as a possible homeostatic element for changes in cortical excitability induced by repetitive transcranial magnetic stimulation

Publication date: Available online 24 February 2018
Source:Brain Stimulation
Author(s): Danny Jazmati, Ute Neubacher, Klaus Funke
BackgroundRepetitive transcranial magnetic stimulation (rTMS) is able to modify cortical excitability. Rat rTMS studies revealed a modulation of inhibitory systems, in particular that of the parvalbumin-expressing (PV+) interneurons, when using intermittent theta-burst stimulation (iTBS).ObjectiveThe potential disinhibitory action of iTBS raises the questions of how neocortical circuits stabilize excitatory-inhibitory balance within a physiological range. Neuropeptide Y (NPY) appears to be one candidate.MethodsAnalysis of cortical expression of PV, NPY and vesicular glutamate transporter type 1 (vGluT1) by immunohistochemical means at the level of cell counts, mean neuropil expression and single cell pre-/postsynaptic expression, with and without intraventricular NPY-injection.ResultsOur results show that iTBS not only reduced the number of neurons with high-PV expression in a dose-dependent fashion, but also increased the cortical expression of NPY, discussed to reduce glutamatergic transmission, and this was further associated with a reduced vGluT1 expression, an indicator of glutamateric presynaptic activity. Interneurons showing a low-PV expression exhibit less presynaptic vGluT1 expression compared to those with a high-PV expression. Intraventricular application of NPY prior to iTBS prevented the iTBS-induced reduction in the number of high-PV neurons, the reduction in tissue vGluT1 level and that presynaptic to high-PV cells.ConclusionsWe conclude that NPY, possibly via a global but also slow homeostatic control of glutamatergic transmission, modulates the strength and direction of the iTBS effects, likely preventing pathological imbalance of excitatory and inhibitory cortical activity but still allowing enough disinhibition beneficial for plastic changes as during learning.



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Déjà-rêvé: Prior dreams induced by direct electrical brain stimulation

Publication date: Available online 24 February 2018
Source:Brain Stimulation
Author(s): Jonathan Curot, Luc Valton, Marie Denuelle, Jean-Pierre Vignal, Louis Maillard, Jérémie Pariente, Agnès Trébuchon, Fabrice Bartolomei, Emmanuel J. Barbeau
BackgroundEpileptic patients sometimes report experiential phenomena related to a previous dream they had during seizures or electrical brain stimulation (EBS). This has been alluded to in the literature as "déjà-rêvé" ("already dreamed"). However, there is no neuroscientific evidence to support its existence and this concept is commonly mixed up with déjà-vu. We hypothesized that déjà-rêvé would be a specific entity, i.e., different from other experiential phenomena reported in epileptic patients, induced by EBS of specific brain areas.MethodsWe collected all experiential phenomena related to dreams induced by electrical brain stimulations (EBS) in our epileptic patients (2003–2015) and in a review of the literature. The content of these déjà-rêvé and the location of EBS were analyzed.ResultsWe collected 7 déjà-rêvé in our database and 35 from the literature, which corresponds to an estimated prevalence of 0.3‰ of all EBS-inducing déjà-rêvé. Déjà-rêvé is a generic term for three distinct entities: it can be the recollection of a specific dream ("episodic-like"), reminiscence of a vague dream ("familiarity-like") or experiences in which the subject feels like they are dreaming (literally "a dreamy state"). EBS-inducing "episodic-like" and "familiarity-like" déjà-rêvé were mostly located in the medial temporal lobes. "Dreamy states" were induced by less specific EBS areas although still related to the temporal lobes.ConclusionsThis study demonstrates that déjà-rêvé is a heterogeneous entity that is different from déjà-vu, the historical "dreamy state" definition and other experiential phenomena. This may be relevant for clinical practice as it points to temporal lobe dysfunction and could be valuable for studying the neural substrates of dreams.



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Intraventricular Epithelioid Glioblastoma: A Case Report

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Naoki Nitta, Suzuko Moritani, Tadateru Fukami, Yayoi Yoshimura, Hisao Hirai, Kazuhiko Nozaki
BackgroundEpithelioid glioblastoma, a high-grade, diffuse astrocytic tumor variant, comprises closely packed epithelioid cells and rhabdoid cells. This rare tumor usually develops in the cerebral cortex and diencephalon; however, in the case reported here, it was located intraventricularly.Case DescriptionA 47-year-old woman was referred to our hospital with a right intraventricular mass that had rapidly increased in size. On discovery of the tumor 3 years earlier at the referring hospital, the mass was small, calcified, and attached to the periventricular parenchyma. Over the next 2 years, the mass grew slowly, as observed on periodic magnetic resonance imaging scans. Forty days before the referral, the patient experienced headache and nausea, and marked growth and intratumoral hemorrhage were visible on a computed tomography scan of the head. The tumor was partially removed via a superior parietal lobule corticotomy. Histopathological examination confirmed an isocitrate dehydrogenase–wild-type epithelioid glioblastoma with a BRAF V600E mutation, but the original slow-growing lesion was no longer detected. Consequently, we assume that in this case, a low-grade glioma transformed into an aggressively malignant epithelioid glioblastoma.ConclusionsWe present the first case of an intraventricular epithelioid glioblastoma that might have arisen from a low-grade glioma with calcification. We recommend including this tumor variant in the differential diagnosis of lateral ventricle tumors.



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Spontaneous Cervical Spinal Epidural Hematoma Associated with Dabigatran

Publication date: April 2018
Source:World Neurosurgery, Volume 112
Author(s): Quentin Mathais, Pierre Esnault, Maximilien Cruc, Cedric Bernard, Bertrand Prunet, Pierre Emmanuel Gaillard
BackgroundWhile spontaneous spinal epidural hematomas are rare, 1 of the identified risk factors is vitamin K antagonist therapy.Case DescriptionWe present a case of a spontaneous spinal epidural hematoma occurring in a patient under treatment with dabigatran, a non–vitamin K oral anticoagulant. The initial hemiparesis symptom was misleading and was retrospectively identified as Brown-Séquard syndrome. Immediate dabigatran antagonism with idarucizumab followed by posterior cervical laminectomy permitted a complete neurologic recovery at day 4.ConclusionsThis is the first description of a spontaneous spinal epidural hematoma under non−vitamin K antagonist oral anticoagulant therapy that has been successfully antagonized and emphasizes the importance of specific antidote development.



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Impact of time-related factors on biologically accurate radiotherapy treatment planning

Abstract

Background

The incomplete repair (IR) model expresses the cell repair effect from radiation-induced damage over time, which is given little consideration in actual treatment planning. By incorporating the IR model into the normal tissue complication probability (NTCP), the accuracy and safety of treatment plan evaluations concerning the effect of repair can be improved. This study aims to evaluate the impact of incorporating the IR model into the NTCP by varying time-related factors such as the repair half-time (T_1/2) and the junction-shift sc3hedule in craniospinal irradiation (CSI).

Methods

CSI was planned retrospectively, and the NTCP of the spinal cord was calculated with the IR model for values of T_1/2 from 1 to 10 h. The NTCP in the case of changing the junction-shift schedule was also examined in the same manner.

Results

The NTCP with the IR model increased with increasing T_1/2, which is prominent for the larger T_1/2. By changing the junction-shift schedule, the NTCP with the IR model decreased when adjacent fields overlapped.

Conclusions

The IR model is a valuable addition to treatment planning because it enables the NTCP to be evaluated including the effect of repair and differences in scheduling to be reflected in the NTCP. However, these are largely dependent on the value of the T_1/2.

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Dosimetric impact of tumor treating field (TTField) transducer arrays onto treatment plans for glioblastomas – a planning study

Abstract

Background

Tumor-Treating Fields (TTFields) are a novel treatment strategy for glioblastoma (GBM) that is approved for the use concomitantly to adjuvant chemotherapy. Preclinical data suggest a synergistic interaction of TTFields and radiotherapy (RT). However, the dosimetric uncertainties caused by the highly dense arrays have led to caution of applying the TTF setup during RT.

Methods

In a RW3 slab phantom we compared the MV- and kV-CT based planned dose with the measured dose. VMAT-plans were optimized on MV-CTs of an Alderson head phantom without TTF arrays and then re-calculated on the same phantom equipped with TTF arrays. Dose at organs at risk (OAR) and target volumes (PTVs) were compared.

Results

Measurements at a depth of 2, 3 and 4 cm of a RW 3 slab phantom show an attenuation due to TTField arrays of 3.4, 3.7 and 2.7% respectively. This was in-line with calculated attenuations based on MV-CT (1.2, 2.5 and 2.5%) but not with the attenuation expected from kV-CT based calculations (7.1, 8.2 and 8.6%). Consecutive MV-CT based VMAT planning and re-calculation reveals, that the conformity and homogeneity are not affected by the presence of TTField arrays. The dose at organs at risk (OAR) can show increases or decreases by < 0.5 Gy, which should be considered especially in cases next to the scull base.

Conclusion

MV-CT based dose calculation results in reliable dose distributions also in the presence of TTField arrays. There is a small but clinically not relevant interaction between the TTField arrays and VMAT dose application. Thus, daily replacement of TTField arrays is not necessary in regard to deeply located OARs. RT is feasible, when a VMAT treatment plan is optimized to an array free planning CT. As the biologic effect of a concomitant treatment especially on OARs is currently unknown, a concomitant treatment should be performed only within clinical trials.

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Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment

Abstract

Background

We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy.

Methods

We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (D_max) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy.

Results

A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26–77 years), and 14 (53.8%) had grade III/IV tumors. The median D_max to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD_2/2), was 7.4 Gy₂ (0.7–13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were − 7.7% (95% confidence interval [CI], − 19.6% to 4.2%), − 9.2% (95% CI, − 25.4% to 7.0%), and − 3.4% (− 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration.

Conclusions

The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.

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Unresectable hepatic PEComa: a rare malignancy treated with stereotactic body radiation therapy (SBRT) followed by complete resection

Abstract

Background

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors occurring in various anatomic regions. Although diagnostic criteria and treatment management are not established, current treatment options consist of surgery and chemotherapy including mTOR inhibitors.

Stereotactic body radiation therapy (SBRT) is a non-invasive ablative treatment which has shown excellent control rates for more common types of unresectable liver tumors and metastases. In this report we present a rare case of PEComa of the liver that was treated by stereotactic radiotherapy followed by resection. Staging and evaluation of treatment response was done by FDG-PET/CT. This case highlights the potential of SBRT as a neoadjuvant treatment even for rare liver malignancies. It is the first case of liver PEComa treated by SBRT and resection.

Case presentation

A 52-year-old woman presented at an external hospital with abdominal pressure and pain in the right upper abdominal quadrant. A CT scan showed a 700 cm³ liver lesion in segment IV. In repeated biopsy in July 2015 histopathological workup showed a pleomorphic epitheloid tumor with small to medium sized cells expressing vimentin and melan-A while being negative for cytokeratin establishing the diagnosis of PEComa of the liver.

To achieve high, ablative doses a stereotactic body radiotherapy (SBRT) technique was chosen consisting of 60Gy (biologically effective dose 105Gy) in 8 fractions of 7.5Gy. Radiotherapy planning was based on MRI resulting in a planning target volume (PTV) of 1944 cm³. Treatment toxicity was limited to a slight elevation of transaminases (grade 1 and 3). A complete resection was performed 21 weeks after radiotherapy confirmed by negative surgical margins.

At last follow-up 21 months after therapy, MRI showed neither local nor distant tumor recurrence. The patient was in stable condition (ECOG 1) and without late radiation toxicity.

Conclusions

This is the first documented case of liver PEComa treated by SBRT and resection. A favorable post-treatment course demonstrates that SBRT is a potential neoadjuvant treatment that is capable of reducing an inoperable rare liver tumor to a resectable lesion.

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Monitoring of mechanical errors and their dosimetric impact throughout the course of non-coplanar continuous volumetric-modulated arc therapy

Abstract

Background

Volumetric-modulated Dynamic WaveArc therapy (VMDWAT) is a non-coplanar continuous volumetric modulated radiation therapy (VMAT) delivery technique. Here, we monitored mechanical errors and their impact on dose distributions in VMDWAT using logfiles throughout the course of treatment.

Methods

Fifteen patients were enrolled (2 skull base tumor patients and 13 prostate cancer patients). VMDWAT plans were created for the enrolled patients. The prescribed dose for the skull base tumor was set as 54 Gy at 1.8 Gy per fraction, and that for the prostate cancer was set as 72 to 78 Gy at 2 Gy per fraction. We acquired logfiles to monitor mechanical errors and their impact on dose distribution in each fraction. The root mean square error (RMSE) in the multi-leaf collimator (MLC), gantry angle, O-ring angle and monitor unit (MU) were calculated using logfiles throughout the course of VMDWAT for each patient. The dosimetric impact of mechanical errors throughout the course of VMDWAT was verified using a logfile-based dose reconstruction method. Dosimetric errors between the reconstructed plans and the original plans were assessed.

Results

A total of 517 datasets, including 55 datasets for the 2 skull base tumor patients and 462 datasets for the 13 prostate cancer patients, were acquired. The RMSE values were less than 0.1 mm, 0.2°, 0.1°, and 0.4 MU for MLC position, gantry angle, O-ring angle, and MU, respectively. For the skull base tumors, the absolute mean dosimetric errors and two standard deviations throughout the course of treatment were less than 1.4% and 1.1%, respectively. For prostate cancer, these absolute values were less than 0.3% and 0.5%, respectively. The largest dosimetric error of 2.5% was observed in a skull base tumor patient. The resultant dosimetric error in the accumulated daily delivered dose distribution, in the patient with the largest error, was up to 1.6% for all dose-volumetric parameters relative to the planned dose distribution.

Conclusions

MLC position, gantry rotation, O-ring rotation and MU were highly accurate and stable throughout the course of treatment. The daily dosimetric errors due to mechanical errors were small. VMDWAT provided high delivery accuracy and stability throughout the course of treatment.

Trial registration

UMIN000023870. Registered: 1 October 2016.

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Stereotactic Body Radiotherapy (SBRT) for liver metastasis – clinical outcomes from the international multi-institutional RSSearch® Patient Registry

Abstract

Background

Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry.

Methods

Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED₁₀. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test.

Results

The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31–91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm³ (1.6–877 cm³), median SBRT dose was 45 Gy (12–60 Gy) delivered in a median of 3 fractions [1–5]. At a median follow-up of 14 months (1–91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p < 0.0001). Smaller tumor volumes (< 40 cm³) correlated with improved OS (25 months vs 15 months p = 0.0014). BED₁₀ ≥ 100 Gy was also associated with improved OS (27 months vs 15 months p < 0.0001). Local control (LC) was evaluable in 430 liver metastases from 324 patients. Two-year LC rates was better for BED₁₀ ≥ 100 Gy (77.2% vs 59.6%) and the median LC was better for tumors < 40 cm³ (52 vs 39 months). There was no difference in LC based on histology of the primary tumor.

Conclusions

In a large, multi-institutional series of patients with liver metastasis treated with SBRT, reasonable LC and OS was observed. OS and LC depended on dose and tumor volume, while OS varied by primary tumor. Future prospective trials on the role of SBRT for liver metastasis from different primaries in the setting of multidisciplinary management including systemic therapy, is warranted.

Trial registration

Clinicaltrials.gov: NCT01885299.

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Optimizing the prescription isodose level in stereotactic volumetric-modulated arc radiotherapy of lung lesions as a potential for dose de-escalation

Abstract

Background

To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de–escalation in stereotactic body radiotherapy for non–small cell lung carcinomas (NSCLC).

Methods

For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re–normalized to the median gross tumor volume dose (GTV–based prescription) to assess the impacts of PTV and normal tissue dose reduction.

Results

With PTV–based prescription, GTV mean dose was much higher with the optimized PIL at 60% with significant reduction of normal lung receiving 30 to 10 Gy (V_30–10Gy ), and observable but insignificant dose reduction to spinal cord, esophagus, ribs, and others compared with 85% PIL. Mean doses to the normal lung between PTV and GTV was higher with 60–70% PIL than 85%. The dose gradient index was 5.0 ± 1.1 and 6.1 ± 1.4 for 60 and 85% PIL (p < 0.05), respectively. Compared with the reference 85% PIL plan using PTV–base prescription, significant decreases of all normal tissue doses were observed with 60% and 70% PIL by GTV–based prescription. Yet, the resulting biological effective (BED) mean doses of PTV remain sufficiently high, ranging 104.2 to 116.9 Gy _{α/β = 10}.

Conclusions

Optimizing the PIL with VMAT has notable advantage of improving the dosimetric quality of lung SBRT and offers the potential of dose de–escalation for surrounding tissues while increasing the GTV dose simultaneously. The clinical implication of re–normalizing plans from PTV–prescription at 60–70% to the GTV median dose requires further investigations.

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Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma

Abstract

Background

The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy.

Methods

A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue.

Results

Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart.

Conclusions

When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

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Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases

Abstract

Background

The objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice.

Methods

Data were provided by the population-based Munich Cancer Registry. Between 1998 and 2014, 1048 female patients with diagnosis of DCIS and treated at two Breast Care Centres were included in this observational study. The effectiveness of postoperative radiotherapy and variables predicting the use of radiotherapy were retrospectively analysed.

Results

After adjusting for age, tumour characteristics and therapies, Cox regression analysis for local recurrence-free survival identified RT as an independent predictor for improved local control (HR: 0.579; 95%CI: 0.384–0.872, p = 0.008). Ten-year cumulative incidence of in-breast recurrences was 20.0% following BCS, compared to 13.6% in patients receiving postoperative radiotherapy (p = 0.012). As an estimate for disease-specific survival, 10-year relative survival was 105.4% for patients receiving postoperative radiotherapy and 101.6% without radiotherapy. On multivariate analysis, postoperative radiotherapy was not associated with improved overall survival (HR 0.526; 95%CI: 0.263–1.052, p = 0.069). Over time, a significant increase of RT was registered: while 1998 only 42.9% of patients received postoperative radiotherapy, the proportion rose to 91.2% in 2014. Women aged < 50 years (OR: 2.559, 95%CI: 1.416–4.625, p < 0.001) or with negative hormone receptor status (OR: 2.625, 95%CI: 1.458–4.728, p = 0.001) or receiving endocrine therapy (OR: 1.762, 95%CI: 1.060–2.927, p = 0.029) were more likely to receive postoperative radiotherapy after BCS.

Conclusions

In conclusion, this study provides insights regarding the adoption and treatment pattern of postoperative RT following BCS for DCIS in a large cohort reflecting "real-life" clinical practice in this setting. Postoperative RT was found to be associated with a reduced risk of ipsilateral recurrence and no survival benefit compared to observation alone.

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Early evaluation of radiation-induced parotid damage in patients with nasopharyngeal carcinoma by T2 mapping and mDIXON Quant imaging: initial findings

Abstract

Background

Radiation-induced parotid damage is a common complication in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy to head and neck region, which severely reduce the life quality of those patients. The aim of this study was to early evaluate the changes of irradiated parotid glands with T2 mapping and mDIXON Quant imaging.

Methods

Forty-one patients with NPC underwent conventional magnetic resonance imaging for nasopharynx and neck, and T2 mapping and mDIXON Quant imaging for bilateral parotid glands within 2 weeks before radiotherapy (pre-RT), 5 weeks after the beginning of radiotherapy (mid-RT), and 4 weeks after radiotherapy (post-RT). Parotid volume, T2 values, fat fraction (FF) values, and mean radiation dose were recorded and analyzed.

Results

From pre-RT to mid-RT, parotid volume decreased (atrophy rate, 27.0 ± 11.5%), while parotid T2 and FF values increased (change rate, 6.0 ± 6.2% for T2 value and 9.1 ± 9.9% for FF value) significantly. From mid-RT to post-RT, parotid T2 value continuously increased (change rate, 4.6 ± 7.7%), but parotid FF value decreased (change rate, − 9.9 ± 18.2%) significantly. Change rate of parotid T2 value significantly correlated with parotid atrophy rate from pre-RT to post-RT (r = 0.313, P = 0.027). Multiple linear regression analysis showed that parotid T2 value (standardized coefficient [SC] = − 0.259, P = 0.001) and FF value (SC = − 0.320, P = 0.014) negatively correlated with parotid volume, while parotid T2 value positively correlated with MR scan time point (SC = 0.476, P = 0.001) significantly. Parotid T2 and FF values showed excellent reproducibility (intraclass correlation coefficient, 0.935–0.992).

Conclusions

T2 mapping and mDIXON Quant imaging is useful for noninvasive evaluation of radiation-induced parotid damage.

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1x8 Gy versus 5x4 Gy for metastatic epidural spinal cord compression: a matched-pair study of three prognostic patient subgroups

Abstract

Background

This study provides separate comparisons of 1 × 8 Gy to 5 × 4 Gy for metastatic epidural spinal cord compression (MESCC) in patients with poor, intermediate and favorable survival prognoses.

Methods

Patients receiving 1 × 8 Gy were matched to patients receiving 5 × 4 Gy for age, gender, performance status, tumor type, involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, ambulatory status and time developing motor deficits. From a study including patients with poor (N = 156) or intermediate (N = 86) survival prognoses, subgroup analyses were performed. Furthermore, 232 new patients with favorable prognoses matched the same way were included.

Results

In poor prognoses patients, 6-month survival rates were 10% after 1 × 8 Gy and 6% after 5 × 4 Gy (p = 0.38); in-field reRT rates in few patients alive at 6 months were 15 and 2% (p = 0.16). In intermediate prognoses patients, 6-month survival rates were 49% after 1 × 8 Gy and 58% after 5 × 4 Gy (p = 0.30). ReRT rates at 6 months were 23 and 13% (p = 0.25). In favorable prognoses patients, 6-month survival rates were 89% after 1 × 8 Gy and 91% after 5 × 4 Gy. ReRT rates at 6 months were 14 and 3% (p = 0.007). In no subgroup, RT regimen had a significant impact on motor function.

Conclusions

Since in patients with poor prognoses, outcomes after 1 × 8 Gy and 5 × 4 Gy were not significantly different, 1 × 8 Gy may be an option. In patients with intermediate prognoses, a trend was found in favor of 5 × 4 Gy. In patients with favorable prognoses, need for in-field reRT was greater after 1 × 8 Gy.

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Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning

Abstract

Background

To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients.

Methods

Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing.

Results

Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 – 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 – 8%).

Conclusions

We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing.

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Clinical results of proton beam therapy for elderly patients with non-small cell lung cancer

Abstract

Background

The purpose of the present study was to evaluate retrospectively the efficacy and safety of proton beam therapy for elderly patients (≥80 years of age) with non-small cell lung cancer.

Methods

Patients diagnosed with T1–4 N0 M0 non-small cell lung cancer and treated with proton beam therapy between January 2009 and 2015 were recruited from our database retrospectively. Toxicity was evaluated using The Common Terminology Criteria for Adverse Events version 4.0.

Results

Thirty-five patients, including 25 (71%) with clinically inoperable lung cancer, were administered proton beam therapy. The median age was 82 years (range: 80–87 years), and the median follow-up time was 34 months (range: 10–72 months). The median dose of proton beam therapy was 80.0 Gy relative biological effectiveness (RBE) (range: 60.0–80.0 Gy [RBE]), and all patients completed the treatments. All patients were followed for at least 23 months or until their death. The 3-year overall survival rate was 67.2% (90.0% in patients with operable lung cancer, and 58.2% in those with inoperable lung cancer). The 3-year local control rate was 86.5%. Two patients presented with grade 2 pneumonitis. The occurrence rate of grade 2 pneumonitis was significantly correlated with a high lung V20 (p = 0.030), and a high mean lung dose (p = 0.030), and a low ratio of lung volume spared from 0.05 Gy (RBE) dose (total lung volume minus lung volume irradiated at least 0.05 Gy [RBE]) (p = 0.030). However, there were no cases of grade 3 or higher radiation pneumonitis.

Conclusions

This study suggests that the proton beam therapy was feasible for elderly patients with non-small cell lung cancer and can be considered as one of the treatment choices for elderly patients with lung cancer.

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Side effects of CT-guided implantation of 125 I seeds for recurrent malignant tumors of the head and neck assisted by 3D printing non co-planar template

Abstract

Background

For the recurrence of head and neck cancer after operation and radiotherapy, the local control of radioactive seed implantation is good, and it has a certain palliative effect. This study aims to investigate the acute and late side effects of a three-dimentional printing non co-planar template (3D–PNCT) for computed tomography (CT)-guided radioactive ¹²⁵I seed (RIS) implantation in recurrent cancer of the head and neck.

Methods

Between January 2016 and December 2016, forty-two patients with local recurrent malignant tumors of the head and neck received 3D–PNCT-assisted RIS implantation. The prescribed dose was 110–160 Gy. Preoperative planning design, production of individual guide plates, RIS implantation, postoperative dose evaluation, and follow-up were completed for all patients. Side effects in the skin, mucous membranes, blood and spinal cord were evaluated.

Results

All patients underwent surgery successfully. Duration of follow-up was 4–14 (median, of 8.5) months. The activity of a single RIS was 0.34–0.7 (median, 0.6) mCi. The number of RIS was 10–126 (median, 34). The number of implantation needles was 4–31 (median, 11). The mean D2cc (dose to the most exposed 2-cc volume) and D0.1cc (dose to the most exposed 0.1-cc volume) of the skin were 24.9 (7.1–85.5) and 47.5 (9.4–167.2), respectively, whereas those of the spinal cord were 8.4 (4.5–33.3) and 14.2 (13.6–63.0), mucosa were 35.1 (4.2–82.8) and 87.0 (6.6–214.1), parotid glands were 16.2 (12.8–19.7) and 29.8 (26.1–33.4) and those of the trachea were 17.9 (2.5–45.9) and 32.7 (3.9–83.9), respectively. No case had an acute reaction of grade ≥ 3. Three cases had a grade-1 skin reaction. Blood toxicity did not occur, nor spinal-cord injury. Xerostomia was not aggravated than that of before brachytherapy. One case had a grade-3 nerve response.

Conclusions

3D–PNCT-assisted RIS implantation can provide good accuracy for positioning. For local recurrent malignant tumor of head and neck, there were no obvious adverse reactions.

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From IB2 to IIIB locally advanced cervical cancers: report of a ten-year experience

Abstract

Background

Despite screening campaigns, cervical cancers remain among the most prevalent malignancies and carry significant mortality, especially in developing countries. Most studies report outcomes of patients receiving the usual standard of care. It is possible that these selected patients may not correctly represent patients in a real-world setting, which may be a limitation in interpreting outcomes. This study was undertaken to identify prognostic factors, management strategies and outcomes of locally advanced cervical cancers (LACC) treated in daily clinical practice.

Methods

Medical files of all consecutive patients treated with curative intent for LACC in a French Cancer Care Center between 2004 and 2014 were reviewed retrospectively.

Results

Ninety-four patients were identified. Performance status was ≥ 2 in 10.6%. Median age at diagnosis was 63.0. Based on the International Federation of Gynecology and Obstetrics classification, tumours were classified as follows: 10.6% IB2, 22.3% IIA, 51.0% IIB, 4.3% IIIA and 11.7% IIIB. Pelvic lymph nodes were involved in 34.0% of cases. Radiotherapy was delivered for all patients. Radiotherapy technique was intensity modulated radiation therapy or volumetric modulated arc therapy in 39.4% of cases. A concurrent cisplatin chemotherapy was delivered in 68.1% of patients. Brachytherapy was performed in 77.7% of cases. The recommended standard care (concurrent chemoradiotherapy with at least five chemotherapy cycles during radiotherapy, followed by brachytherapy) was delivered in 43.6%. The median overall treatment time was 56 days. Complete tumour sterilisation was achieved in 55.2% of cases. Mean follow-up was 54.3 months. Local recurrence rate was 18.1%. Five-year overall survival was 61.9% (95% Confident Interval (CI) = 52.3–73.2) and five-year disease-specific survival was 68.5% (95% CI = 59.2–79.2). Poor performance status, lymph nodes metastasis and absence of concurrent chemotherapy were identified as poor prognostic factors in multivariate analysis.

Conclusions

Less than 50% of patients received the standard care. Because LACC patients and disease are heterogeneous, treatment tailoring appears to be common in current clinical practice. However, guidelines for tailoring management are not currently available. More data about real-world settings are required in order to to optimise clinical trials' aims and designs, and make them translatable in daily clinical practice.

Trial registration

retrospectively registered.

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Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

Abstract

Background

To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.

Methods

Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.

Results

For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D₅₀ = 64.2Gy, m = 0.50, n = 1.0; 2) D₅₀ = 95.0Gy, m = 0.45, n = 0.50; 3) D₅₀ = 83.1Gy, m = 0.56, n = 1.00; and 4) D₅₀ = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.

Conclusions

Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

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Evaluation of the tumor movement and the reproducibility of two different immobilization setups for image-guided stereotactic body radiotherapy of liver tumors

Abstract

Background

The purpose of this study is to evaluate the tumor movement and accuracy of patient immobilization in stereotactic body radiotherapy of liver tumors with low pressure foil or abdominal compression.

Methods

Fifty-four liver tumors treated with stereotactic body radiotherapy were included in this study. Forty patients were immobilized by a vacuum couch with low pressure foil, 14 patients by abdominal compression. We evaluated the ratio of gross tumor volume/internal target volume, the tumor movement in 4D-computed tomography scans and daily online adjustments after cone beam computed tomography scans.

Results

The ratio of gross tumor volume/internal target volume was smaller with low pressure foil. The tumor movement in 4D-computed tomography scans was smaller with abdominal compression, the cranial movement even significantly different (p = 0.02). The mean online adjustments and their mean absolute values in the vertical, lateral and longitudinal axis were smaller with abdominal compression. The online adjustments were significantly different (p < 0.013), their absolute values in case of the longitudinal axis (p = 0.043). There was no significant difference of the adjustments' 3D vectors.

Conclusions

In comparison to low pressure foil, abdominal compression leads to a reduction of the tumor movement. Online adjustments decreased significantly, thus leading to higher accuracy in patient positioning.

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HyperArc VMAT planning for single and multiple brain metastases stereotactic radiosurgery: a new treatment planning approach

Abstract

Purpose

The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT).

Material and methods

For 23 patients (1–4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20–24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V_2Gy-V_16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared.

Results

HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p < 0.01), CI (0.93 ± 0.02 vs. 0.90 ± 0.05, p = 0.01) and lower GI (3.06 ± 0.42 vs. 3.91 ± 0.55, p < 0.01) values. Moderate-to-low dose spreads (V_4Gy-V_16Gy) were significantly reduced (p < 0.01) in the HA-VMAT plan over that of C-VMAT. HA-VMAT plans resulted in more complex MLC patterns (lower MCSV, p < 0.01) and higher MU (p < 0.01).

Conclusions

HA-VMAT plans provided significantly higher conformity and rapid dose falloff with respect to the C-VMAT plans.

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Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control

Abstract

Background

Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1.

Methods

We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated.

Results

The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures.

Conclusions

Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.

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Prognostic Factors in the Era of Targeted Therapies in CLL

Abstract

Purpose of Review

Chronic lymphocytic leukemia is heterogeneous disease characterized by a variable clinical course that is greatly influenced by various patient and disease characteristics. Over the last two decades, advent of new diagnostic methodologies has led to the identification of several factors of prognostic and predictive relevance. Furthermore, recent advances in next-generation sequencing techniques has identified recurrent novel mutations in NOTCH1, SF3B1, BIRC3, and ATM genes whose role as prognostic and predictive markers is currently being investigated. These biologic markers carry new prognostic information and their incorporation into prognostic scoring systems will likely lead to refined multi-parameter risk models.

Recent Findings

While the prognostic impact of many of the most commonly used markers on clinical outcomes in patients treated with chemo-immunotherapy is well documented, it is important to review their predictive and prognostic role in the era of novel targeted therapies.

Summary

This article will discuss the currently available information on the clinical relevance of prognostic markers in patients treated with novel targeted therapies.

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Common Adverse Effects of Novel Therapies for Multiple Myeloma (MM) and Their Management Strategies

Abstract

Purpose of Review

The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor.

Recent Findings

There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class. Additionally, several agents have critically important drug-drug interactions or dose-modification implications in hepatic or renal insufficiency that can be easily overlooked, and exacerbate adverse effects.

Summary

As treatment of MM moves from fixed-duration traditional chemotherapy to novel agent-based regimens, commonly administered continuously until disease progression or intolerable toxicities, providers must adopt their management strategies for both acute and long-term adverse effects. Early and frequent monitoring for therapy-related complications, dose adjustments when needed, and timely treatment for toxicities are all important steps toward ensuring longevity of treatment from a limited array of therapeutic options that currently exist for a disease with a relapsing and remitting course.

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Recent Developments in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia

Abstract

Purpose of review

Adolescent and Young Adult (AYA) Oncology is a relatively new field encompassing research in the unique pathophysiology, clinical care, and psychosocial issues facing patients between the ages of 15 and 40 with cancer. About 100,000 of the approximately 1.5 million people diagnosed annually with cancer in the USA are in this age range. This chapter will review notable new developments in the care of adolescents and young adults with acute lymphoblastic leukemia (ALL) within the last 3 years.

Recent findings

The preponderance of data favors the treatment of AYA ALL patients with pediatric-inspired treatment regimens due to better relapse-free and overall survival. Minimal residual disease (MRD) measurement is emerging as an important prognostic factor and can serve as a new measure of efficacy of the addition of novel therapies to the treatment of patients with new diagnoses. There have been several treatment advances ranging from new cytotoxic agents for ALL to new antibody-based therapy to novel immune therapies such as CAR-T cells.

Summary

The care of AYA ALL patients is improving as the unique issues for this patient population are addressed.

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Updates of Peripheral T Cell Lymphomas Based on the 2017 WHO Classification

Abstract

Purpose of Review

This review will describe and update the readers on the recent changes of the 2017 WHO classification in regard to peripheral T cell lymphomas.

Recent Findings

Significant advances in molecular studies have resulted in revisions of the classification as well as introduction of provisional entities (such as breast implant-associated ALCL, nodal PTCL with TFH phenotype).

Summary

Major advances in molecular and gene expression profiling have expanded our knowledge of T cell lymphomas, including updates in the diagnostic criteria and sub-classification which will facilitate in improving patient care and research.

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“Existential Fridays”—reflection in action

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Molecular characterization and multidisciplinary management of Gerbich hemolytic disease of the newborn

Abstract

Gerbich (Ge) antigens are high frequency red cell antigens expressed on glycophorin C (GYPC) and glycophorin D. Hemolytic disease of the fetus and newborn (HDFN) due to Gerbich antibody is rare and presents a clinical challenge, as Gerbich negative blood is scarce. We report a case of HDFN due to maternal Ge3 negative phenotype and anti-Ge3 alloimmunization, successfully managed by transfusion of maternal blood. Molecular testing revealed that the mother has homozygous deletion of exon 3 of GYPC, the father is homozygous wildtype for GYPC, and the infant is obligate heterozygote expressing Ge3.

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Mutiple DICER1-related lesions associated with a germline deep intronic mutation

Abstract

Germline DICER1 pathogenic variants predispose to numerous benign and malignant tumors. In this report, we describe DICER1 gene analysis in an adolescent diagnosed with multinodular goiter, ovarian Sertoli–Leydig cell tumor, and lung cyst. DICER1 mutational screening at the DNA level failed to detect any pathogenic variant. Subsequent messenger RNA (mRNA) analysis revealed a 132 nucleotide intronic sequence exonization. This truncating event was caused by a deep intronic mutation generating a de novo acceptor splice site. This study demonstrates that some undetected DICER1 mutations should be investigated at the mRNA level.

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Dose-escalation is needed for gross disease in high-risk neuroblastoma

Abstract

Background

Locoregional failure is common after subtotal resection in high-risk neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for treatment of high-risk neuroblastoma after gross total resection, the dose needed for local control of patients with gross residual disease at the time of RT is unknown. We sought to evaluate local control after 21–36 Gy RT in patients with high-risk neuroblastoma undergoing subtotal resection.

Methods

All patients with high-risk neuroblastoma who received RT to their primary site from 2000 to 2016 were reviewed. Of the 331 patients who received consolidative RT to their primary site, 19 (5.7%) underwent subtotal resection and were included in our analysis. Local failure (LF) was correlated with biologic prognostic factors and dose of RT.

Results

Median follow-up among surviving patients was 6.0 years. Median RT dose was 25 Gy (range, 21 Gy–36 Gy). The 5-year cumulative incidence of LF among all patients was 17.2%. LF at 5 years was 30% in those who received <30 Gy versus 0% in those who received 30–36 Gy (P = 0.12). There was a trend towards improved local control in patients with tumor size ≤10 cm at diagnosis (P = 0.12). The 5-year event-free and overall survival were 44.9% and 68.7%, respectively.

Conclusion

After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30–36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high-risk neuroblastoma.

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Successful hematopoietic stem cell transplantation for osteopetrosis using reduced intensity conditioning

Abstract

Background

Infantile malignant osteopetrosis (IMO) is an autosomal recessive condition characterized by defective osteoclast activity, with hematopoietic bone marrow transplant being the only available cure. Over the past several years, new conditioning regimes and donor options have emerged, thus extending the possibility of cure to a greater number of patients and improving the outcomes of bone marrow transplant. Here we detail the outcomes of bone marrow transplant in a cohort of 31 patients treated with a combination of fludarabine, treosulphan, thiotepa, and antithymocyte globulin.

Procedures

Thirty-one patients with IMO who underwent hematopoietic stem cell transplantation with fludarabine, treosulphan, thiotepa, and antithymocyte globulin at our center from 2012 to 2017 are retrospectively reviewed in this study. Twenty-six patients were transplanted from 10/10 matched donors (13 from siblings, 11 from unrelated, and two from extended family donors), four from 9/10 matched unrelated donors, and one from a 9/10 matched family donor.

Results

Overall survival was 100% with a median follow-up of 363 days (range 74–1891). There were 12 cases of acute graft versus host disease (GvHD) (38.7%), no cases of veno-occlusive disease, and eight cases of hypercalcemia (25.8%). Almost 80% of patients suffered viral reactivations with two cases of Epstein–Barr-virus-driven post-transplant lymphoproliferative disease. All cases of GvHD and viral reactivation were successfully treated.

Conclusions

We conclude that transplantation in children with IMO using fludarabine, treosulphan, thiotepa, and antithymocyte globulin is safe and effective and should be performed as early as possible following diagnosis, prior to the development of severe disease sequelae.

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Generalized lymphatic anomaly presenting as rhinorrhea and chylous pericardial effusion

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Issue Information

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Adjuvant Therapy for Revision Rhinoplasty of Contracted Nose Using Polydeoxyribonucleotide and Invasive Bipolar Radiofrequency

Summary: Most cases of severely contracted nose require revision rhinoplasty and septoplasty, wherein preoperative and/or intraoperative expansion of nasal soft tissue is necessary for tension-free revision surgery. The present study aimed to evaluate the efficacy and safety of pre- and postoperative adjuvant therapy using polydeoxyribonucleotide (PDRN) and invasive, pulsed-type, bipolar, alternating current radiofrequency (RF) for revision surgery of a contracted nose. In total, 30 patients were treated with 16 sessions (8 preoperative sessions and 8 postoperative sessions) of intralesional injection of PDRN and invasive RF treatment using microneedle electrodes at 1-week intervals. One week after the final combined pretreatment using PDRN and invasive bipolar RF, the skin of contracted noses was sufficiently softened, and nasal skin mobility was notably improved in all the patients. During revision rhinoplasty and septoplasty, the contracted nasal skin in each patient was adequately released for proper covering of the nasal tip without tension. Postoperatively, 8 sessions of adjuvant therapy elicited marked clinical improvements in persistent nasal tip dimpling and contracture, septal deviation, and warping from the incomplete recovery of nasal contracture after revision surgery. In conclusion, our pre- and postoperative adjuvant therapies using PDRN and invasive bipolar RF remarkably improved the therapeutic outcomes of revision rhinoplasty and septoplasty for contracted skin of the nose without major side effects.

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V-shaped Internal Nasal Vestibular Flap for Reconstruction of Iatrogenic Columellar Defect

Summary: Columella is an important structure in the center of the face, and its structural integrity has an important functional, social, and psychological role. Columella reconstruction can be very challenging for surgeons and the ideal technique remains elusive. This article describes a reconstruction technique in a young woman with columella necrosis due to nasal continuous positive airway pressure treatment. The method of reconstruction described here, with a V-shaped internal nasal vestibular flap and a cartilage grafts from lateral crura, is simple and easily reproducible, providing an optimal aesthetic result and in addition the donor site does not create a secondary deformity by disrupting normal anatomy.

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Autonomic function test in progressive lacunar infarction

Objective

Neurological progression is a major problem in managing the patients with acute lacunar infarction. The purpose of this was to investigate whether autonomic dysfunction is associated with neurological progression in patients with acute lacunar infarction.

Materials and Methods

The study comprised 60 patients with acute lacunar infarction. All enrolled subjects underwent autonomic function tests including the 30° head-up tilt test, Valsalva test, heart rate response to deep breathing, and sympathetic skin response. The primary endpoint is the neurological progression, and the secondary endpoint is the 3-month outcome.

Results

Increased initial National Institute of Health stroke scale (NIHSS), decreased time to admission from onset, decreased rise of heart rate in the 30° head-up tilt test, abnormal blood pressure response in the Valsalva test, and decreased rise of systolic blood pressure in stage IV of the Valsalva test are associated with neurological progression of acute lacunar infarction; an abnormal blood pressure response in the Valsalva test is significant in logistic regression analysis of neurological progression. Advanced age, increased initial NIHSS and modified Rankin scale, decreased expiration/inspiration ratio of heart rate to deep breathing, decreased rise of systolic blood pressure in stage IV of the Valsalva test, and neurological progression were associated with an unfavorable 3-month outcome; neurological progression was significant in logistic regression analysis of 3-month outcome.

Conclusions

An abnormal blood pressure change in the Valsalva test is associated with neurological progression in patients with acute lacunar infarction, and neurological progression can induce an unfavorable 3-month outcome.

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Development and validation of Spasticity Index—Amyotrophic Lateral Sclerosis

Objectives

Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS.

Methods

Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life.

Results

A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale—the Spasticity Index for ALS (SI-ALS)—which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life.

Conclusions

The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS.

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Lateral alveolar ridge augmentation procedure using subperiosteal tunneling technique: a pilot study

Abstract

Background

In this research article, we evaluate the use of sub-periosteal tunneling (tunnel technique) combined with alloplastic in situ hardening biphasic calcium phosphate (BCP, a compound of β-tricalcium phosphate and hydroxyapatite) bone graft for lateral augmentation of a deficient alveolar ridge.

Methods

A total of 9 patients with deficient mandibular alveolar ridges were included in the present pilot study. Ten lateral ridge augmentation were carried out using the sub-periosteal tunneling technique, including a bilateral procedure in one patient. The increase in ridge width was assessed using CBCT evaluation of the ridge preoperatively and at 4 months postoperatively. Histological assessment of the quality of bone formation was also carried out with bone cores obtained at the implant placement re-entry in one patient.

Results

The mean bucco-lingual ridge width increased in average from 4.17 ± 0.99 mm to 8.56 ± 1.93 mm after lateral bone augmentation with easy-graft CRYSTAL using the tunneling technique. The gain in ridge width was statistically highly significant (p = 0.0019). Histomorphometric assessment of two bone cores obtained at the time of implant placement from one patient revealed 27.6% new bone and an overall mineralized fraction of 72.3% in the grafted area 4 months after the bone grafting was carried out.

Conclusions

Within the limits of this pilot study, it can be concluded that sub-periosteal tunneling technique using in situ hardening biphasic calcium phosphate is a valuable option for lateral ridge augmentation to allow implant placement in deficient alveolar ridges. Further prospective randomized clinical trials will be necessary to assess its performance in comparison to conventional ridge augmentation procedures.

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The Sand Dollar Sign: A Reliable EUS Image to Identify the Excluded Stomach during EUS-Guided Gastrogastrostomy

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Effects of edaravone, the free radical scavenger, on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of recombinant tissue plasminogen activator

Publication date: Available online 24 February 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Xian-Ru Lee, Gui-Ling Xiang
ObjectivesEdaravone, a free radical scavenger, alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute cerebral infarction. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established therapy for acute cerebral infarction patients. The purpose of this study was to assess the effects of edaravone on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA.Patients and MethodsWe conducted a retrospective cohort study using the database of Ningbo First Hospital. We identified patients who were admitted with a primary diagnosis of acute cerebral infarction and treated with intravenous rtPA(iv-rtPA) within 3 hours of symptom onset from March 1^st in 2014 to October 31^st in 2016.Thenceforth,the patients were divided into 2 groups by treatment with(edaravone group) or without edaravone(non-edaravone group). Glasgow Coma Scale(GCS) scores and mRS score at admission were used. Clinical background, risk factors for acute cerebral infarction hemorrhagic transformation, 7-day mortality, recanalization rate, bleeding complications and blood rheology indexes were collected. We also collected the following factors: National Institutes of Health Stroke Scale scores, barthel index.Results136 patients treated without edaravone during hospitalization were selected in non-edaravone group while edaravone group included 132 patients treated with edaravone during hospitalization. The patient baseline distributions were well balanced between non-edaravone group and edaravone group. The rate of hemorrhagic transformation in non-edaravone group was higher than that in edaravone group (P＜0.05). The NIHSS scores 7 days and 14 days after symptom onset were higher in non-edaravone group than in edaravone group (both P＜0.05). Edaravone group showed a higher recanalization rate and a lower bleeding complications rate at discharge than the non-edaravone group (both P＜0.05). The differences of all the blood rheology indexes between the two groups were statistically significant (all P＜0.05).ConclusionsEdaravone may improve outcomes of acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA.



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Value of the PET/CT 3D Visualization of Head and Neck Squamous Cell Carcinoma extended to Mandible

To study an original 3D visualization of head and neck squamous cell carcinoma extending to the mandible by using [18F]-NaF PET/CT and [18F]-FDG PET/CT imaging along with a new innovative FDG and NaF image analysis using dedicated software. The main interest of the 3D evaluation is to have a better visualization of bone extension in such cancers and that could also avoid unsatisfying surgical treatment later on.

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World Health Organization and Its Initiative for Ear and Hearing Care

The World Health Organization (WHO) addresses ear diseases and hearing loss through its program on prevention of deafness and hearing loss. Recently, the World Health Assembly called for action at global and national levels to tackle the rising prevalence and adverse impact of unaddressed hearing loss. Following a public health approach toward this issue, WHO is focusing on i) raising awareness among policymakers and civil society; and ii) providing technical support to countries for promoting hearing care. Meeting this challenge requires a coordinated global effort with all stakeholders working together to make ear and hearing care accessible to all.

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Immediate Breast Reconstruction among Patients with Medicare and Private Insurance: A Matched Cohort Analysis

Background: By eliminating economic hurdles, the Women's Health and Cancer Rights Act of 1998 represented a paradigm shift in the availability of breast reconstruction. Yet, studies report disparities among Medicare-insured women. These studies do not account for the inherent differences in age and comorbidities between a younger privately insured and an older Medicare population. We examined immediate breast reconstruction (IBR) utilization between a matched pre- and post-Medicare population. Methods: Using the Nationwide Inpatient Sample database (1992–2013), breast cancer patients undergoing IBR were identified. To minimize confounding medical variables, 64-year-old privately insured women were compared with 66-year-old Medicare-insured women. Demographic data, IBR rates, and complication rates were compared. Trend over time was plotted for both cohorts. Result: A total of 21,402 64-year-old women and 25,568 66-year-old women were included. Both groups were well matched in terms of demographic type of reconstruction and complication rates. 72.3% of 64-year-old and 71.2 of % 66-year-old women opted for mastectomy. Of these, 25.5% (n = 3,941) of 64-year-old privately insured and 17.7% (n = 3,213) of 66-year-old Medicare-insured women underwent IBR (P

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Complications following Nipple-Sparing Mastectomy and Immediate Acellular Dermal Matrix Implant-based Breast Reconstruction—A Systematic Review and Meta-analysis

Background: Acellular dermal matrix was introduced in breast reconstruction in 2001 and is gradually becoming a standard component for immediate breast reconstruction and nipple-sparing mastectomy. The reconstructive technique allows for improved aesthetic outcomes. However, there seems to be uncertainty regarding complication rates. The aim of this review was to systematically evaluate complication rates related to this method. Methods: This systematic review was conducted according to the recommendations outlined in the Cochrane Handbook for reviews and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Relevant databases were searched for in the literature concerning the use of acellular dermal matrix in implant-based nipple-sparing mastectomy and immediate breast reconstruction. All studies underwent detailed quality assessment. Summarized outcome rates were computed using meta-analysis. Results: Nine of 1,039 studies were eligible for inclusion yielding 778 procedures. The quality was acceptable for all included studies. The meta-analysis found the rate of skin necrosis to be 11%, nipple necrosis 5%, infection in 12%, hematoma in 1%, treated seroma in 5%, explantation 4%, and unplanned return to the operating room in 9%. Conclusion: The use of acellular dermal matrix in nipple-sparing mastectomy and implant-based breast reconstruction can be done with acceptable complication rates in selected patients. We recommend future studies to include specific definitions when reporting complication rates. Furthermore, future studies should elaborate on demographic characteristics of the included study samples and include predictor analysis to enhance knowledge of high risk patients.

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Treatment Strategies for Hypopigmentation in the Context of Burn Hypertrophic Scars

Dyspigmentation in burn scars can contribute to the development of psychosocial complications after injury and can be detrimental to social reintegration and quality of life for burn survivors. Although treatments for skin lightening to treat hyperpigmentation have been well reviewed in the literature, skin-darkening strategies to treat hypopigmentation have not. The following potential treatment options in the context of burn hypertrophic scar will be discussed: use of the melanocyte-keratinocyte transplantation procedure, use of ectopic synthetic analogues of alpha-melanocyte stimulating hormone to initiate melanogenesis, and use of FK506 to induce melanogenesis. A proposed future direction of research in laser-assisted drug delivery of inducers of local melanin production, with the hope of developing a targeted, effective approach to dyspigmentation in hypertrophic scar is also discussed.

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Earfold Implantable Clip System for Correction of Prominent Ears: Analysis of Safety in 403 Patients

Background: The Earfold system, a new treatment for the correction of prominent ears, consists of 3 components: the Earfold implant, the Earfold introducer, and the Prefold positioner. Methods: This is an interim report based on an ongoing analysis of safety in a series of patients treated for prominent ears with the Earfold implant between February 2013 and September 2014. Safety was assessed based on adverse event reports and the need for implant revision; follow-up is ongoing. Results: Seven surgeons used 1,200 Earfold implants to treat 403 patients (ages, 7–70 years; 63% male); the time since the initial implant procedure now ranges from 30 to 48 months. To date, 145 patients (36%) have returned for a follow-up visit (mean, 7.7 months [range, 1–34 months]). Adverse events requiring intervention have affected 39 of 403 (9.7%) patients; these include implant revisions (n = 17 [4.2%], most often due to implant visibility), skin erosion over the implant (n = 15 [3.7%]), and infection (n = 7 [1.7%]). Bleeding, recurrence of prominence, hematoma, deformity, or adverse scarring did not occur. Conclusions: This interim analysis has shown that Earfold prominent ear correction system is associated with relatively few adverse events that require intervention; a small number of patients experienced infection, implant extrusion, or implant visibility that required revision. Most adverse events were related to either patient selection or technical errors at implantation. It is expected that with continued use of Earfold by surgeons experienced in otoplasty, the adverse event incidence will decrease.

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Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty

Background: It has been proposed that negative pressure wound therapy (NPWT) applied prophylactically to a closed incision may decrease the incidence of wound complications. Patients undergoing reduction mammaplasty are at risk of wound complications such as delayed healing, infection, and dehiscence, and the bilateral nature of the surgery allows for a within-patient randomized study to evaluate incisional NPWT's effect in reducing healing complications. Methods: In this multicenter trial, 200 patients undergoing bilateral reduction mammaplasty were treated with PICO Single-Use NPWT System or standard wound-care dressings randomized to right or left breast for up to 14 days to enable within-patient comparison. Follow-up assessments were conducted to evaluate the difference in incision healing complications up to 21 days postsurgery. Healing complications (for the primary endpoint) were defined as delayed healing (incision not 100% closed by 7 days) and occurrence of dehiscence or infection within 21 days. Individual healing complications were assessed separately as secondary endpoints. Results: Significantly fewer healing complications (primary endpoint) were noted in NPWT-treated breasts [113 (56.8%)] versus standard care [123 (61.8%)]. The difference of 10 (5.0%) patients with fewer healing complications using NPWT was statistically significant (P = 0.004). NPWT also resulted in a significantly lower incidence of dehiscence (secondary endpoint) compared with standard care [32 patients (16.2%) versus 52 patients (26.4%)] by day 21, a relative reduction of 38% (P

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Single-Stage Breast Reconstruction Using an All-In-One Adjustable Expander/Implant

Background: When tissue expansion is necessary in breast reconstruction, a single-stage approach is possible using adjustable expander/implants, with or without the use of acellular dermal matrix. We aimed to present the senior author's single-stage experience over a period of 12 years using combined expander/implants in breast reconstruction. Methods: This is a Single-institution, retrospective review of breast reconstruction with combined expander/implants from 2002 to 2014. Logistic regression was performed to evaluate the impact of multiple variables on long-term outcomes. Results: A total of 162 implants in 105 patients were included in this study. Mean follow-up time was 81.7 months (SD, ± 39.2; range, 15–151). Complication rates were as follows: 0.62% extrusion, 1.2% mastectomy flap necrosis, 1.2% hematoma, 1.9% dehiscence, 2.5% seroma, 4.9% infection, and 15.4% deflation. The following associations were identified by logistic regression: adjuvant radiotherapy and capsular contracture (P = 0.034), tumor size and deflation (P = 0014), and smoking history and infection (P = 0.013). Conclusions: Overall, 81% of breasts were successfully reconstructed in a single stage. Single-stage reconstruction using all-in-one expander/implants reduces costs by eliminating the need for a second procedure under general anesthesia and can achieve results comparable with other alloplastic reconstructions reported in the literature.

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An Enhanced Recovery after Surgery Pathway for Microvascular Breast Reconstruction Is Safe and Effective

Background: The aim of this study was to develop, implement, and evaluate a standardized perioperative enhanced recovery after surgery (ERAS) clinical care pathway in microsurgical abdominal-based breast reconstruction. Methods: Development of a clinical care pathway was informed by the latest ERAS guideline for breast reconstruction. Key features included shortened preoperative fasting, judicious fluids, multimodal analgesics, early oral nutrition, early Foley catheter removal, and early ambulation. There were 3 groups of women in this cohort study: (1) traditional historical control; (2) transition group with partial implementation; and (3) ERAS. Narcotic use, patient-reported pain scores, antiemetic use, time to regular diet, time to first walk, hospital length of stay, and 30-day postoperative complications were compared between the groups. Results: After implementation of the pathway, the use of parenteral narcotics was reduced by 88% (traditional, 112 mg; transition, 58 mg; ERAS, 13 mg; P

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Latissimus Dorsi and Immediate Fat Transfer (LIFT) for Complete Autologous Breast Reconstruction

Background: Despite the popularity of latissimus dorsi (LD) flap in breast reconstruction, a breast implant is often necessary to achieve sufficient volume. Prior reports describe fat grafting to the LD flap as a secondary procedure to correct contour deformities and improve volume. Our institution has instituted autologous breast reconstruction with an LD flap and immediate fat transfer (LIFT). Methods: A retrospective review of all patients undergoing the LIFT procedure was undertaken. Patient age, total volume of fat transfer, length of follow-up, need for adjuvant therapy, and complications were recorded. The procedure begins with harvest of the LD flap and fat. Prior to disorigination of the latissimus muscle, fat is injected into the flap. Flap harvest is then completed and inset to create a breast mound. Results: Eighteen patients underwent LIFT procedures over 3 years with an average follow-up of 8.7 months (range, 2–24). Four breasts (22.2%) had previously received adjuvant radiation therapy. The mean total fat grafting volume was 515.5 mL (range, 325–730) per breast. The average estimated fat graft take was 66.8% (range, 50–80%). Four patients (22.2%) experienced complications. Conclusion: Autologous augmentation of the LD flap with lipotransfer has been used to avoid placement of an implant. We improve the technique by performing lipotransfer during index reconstruction. Furthermore, we perform lipotransfer prior to disorigination of the LD muscle to minimize trauma to the flap and increase the efficiency of fat grafting. Our experience demonstrates that this technique is a viable autologous alternative to microsurgical breast reconstruction.

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Virtual Surgical Planning: The Pearls and Pitfalls

Objective: Over the past few years, virtual surgical planning (VSP) has evolved into a useful tool for the craniofacial surgeon. Virtual planning and computer-aided design and manufacturing (CAD/CAM) may assist in orthognathic, cranio-orbital, traumatic, and microsurgery of the craniofacial skeleton. Despite its increasing popularity, little emphasis has been placed on the learning curve. Methods: A retrospective analysis of consecutive virtual surgeries was done from July 2012 to October 2016 at the University of Montreal Teaching Hospitals. Orthognathic surgeries and free vascularized bone flap surgeries were included in the analysis. Results: Fifty-four virtual surgeries were done in the time period analyzed. Forty-six orthognathic surgeries and 8 free bone transfers were done. An analysis of errors was done. Eighty-five percentage of the orthognathic virtual plans were adhered to completely, 4% of the plans were abandoned, and 11% were partially adhered to. Seventy-five percentage of the virtual surgeries for free tissue transfers were adhered to, whereas 25% were partially adhered to. The reasons for abandoning the plans were (1) poor communication between surgeon and engineer, (2) poor appreciation for condyle placement on preoperative scans, (3) soft-tissue impedance to bony movement, (4) rapid tumor progression, (5) poor preoperative assessment of anatomy. Conclusion: Virtual surgical planning is a useful tool for craniofacial surgery but has inherent issues that the surgeon must be aware of. With time and experience, these surgical plans can be used as powerful adjuvants to good clinical judgement.

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