Cancer Research and Therapeutics

Filamentous bacteriophage: A prospective platform for targeting drugs in phage-mediated cancer therapy Pankaj Garg Journal of Cancer Research and Therapeutics 2019 15(8):1-10 A new modality of targeting therapeutic drugs based on the use of bacteriophage (virus), as an emerging tool for specific targeting and for vaccine development, has been an area of interest for genetic and cancer research. The approach is based on genetic manipulation and modification in the chemical structure of a filamentous bacteriophage that facilitates its application not only for in vivo imaging but also for therapeutic purpose, as a gene delivery vehicle, as drug carriers, and also as an immunomodulatory agent. Filamentous bacteriophage on account of its high surface holding ability with adaptable genetic engineering properties can effectively be used in loading of chemical and genetic drugs specifically on to the targeted lesion location. Moreover, the specific peptides/proteins exhibited on the phage surface can be applied directly as self-navigating drug delivery nanovehicles. The present review article has been framed with an objective to summarize the importance of bacteriophage in phage cancer therapy and to understand the possible future prospective of this approach in developing new tools for biotechnological and genetic research, especially in phage -mediated cancer therapy. Importantly, the peptides or proteins emerging from the surface of a nano carrier will make the expense of such peptides economically more effective as compared to other immunological tools, and this seems to be a potential approach for developing a new nanodrug carrier platform.

Magnetic resonance imaging radiomic feature analysis of radiation-induced femoral head changes in prostate cancer radiotherapy Hamid Abdollahi, Seied Rabi Mahdavi, Isaac Shiri, Bahram Mofid, Mohsen Bakhshandeh, Kazem Rahmani Journal of Cancer Research and Therapeutics 2019 15(8):11-19 Background and Purpose: As a feasible approach, radiotherapy has a great role in prostate cancer (Pca) management. However, Pca patients have an increased risk of femoral head damages including fractures after radiotherapy. The mechanisms of these complications are unknown and time of manifestations is too long; however, they may be predicted by early imaging. The main purpose of this study was to assess the early changes in femoral heads in Pca patients treated with intensity-modulated radiation therapy (IMRT) using multiparametric magnetic resonance imaging (mpMRI) radiomic feature analysis. Materials and Methods: Thirty Pca patients treated with IMRT were included in the study. All patients underwent two mpMRI pre- and postradiotherapy. Thirty-four robust radiomic features were extracted from T1, T2, and apparent diffusion coefficient (ADC) obtained from diffusion-weighted images. Wilcoxon signed-rank test was performed to assess the significance of the change in the mean T1, T2, and ADC radiomic features postradiotherapy relative to preradiotherapy values. The percentage change values were normalized based on the natural logarithm base ten. Features were also ranked based on their median changes. Results: Sixty femoral heads were analyzed. All radiomic features have undergone changes. Significant postradiotherapy radiomic feature changes were observed in 20 and 5 T1- and T2-weighted radiomic features, respectively (P < 0.05). ADC features did not vary significantly postradiotherapy. The mean radiation dose received by femoral heads was 40 Gy. No fractures were observed within the follow-up time. Different features were found as high ranked among T1, T2, and ADC images. Conclusion: Early structural change analysis using radiomic features may contribute to predict postradiotherapy fracture in Pca patients. These features can be identified as being potentially important imaging biomarkers for predicting radiotherapy-induced femoral changes.

Adjuvant radiotherapy after surgical resection for adrenocortical carcinoma: A systematic review of observational studies and meta-analysis Gustavo Arruda Viani, Bruno Silveira Viana Journal of Cancer Research and Therapeutics 2019 15(8):20-26 Purpose: Historically, the role of adjuvant radiotherapy (RT) for patients with adrenocortical carcinoma (ACC) has been controversial. The objective of this research is to review systematically the literature evaluating the role of adjuvant RT in patients with ACC undergone a surgical resection. Materials and Methods: The electronic databases were searched for articles published until July 2017 without language restriction: Lilacs, Medline, Embase, and the Cochrane. Two reviewers independently appraised the eligibility criteria and extracted data. When possible, a fixed-effect meta-analysis was done. The systematic review (SR) followed all the criteria of the MOOSE guideline. Results: Overall, 382 citations were identified. After the screening of titles and abstracts, 12 articles (eight case series [48 patients] and 4 cohort studies [136 patients]) were included in the final analysis. For the local recurrence, the pooled relative risk (RR) was RR = 0.46 (95% confidence interval: 0.28–0.75), in favor of adjuvant RT when compared with surgery alone. Concerning overall mortality and disease recurrence, no significant difference between adjuvant RT and surgery was detected, RR = 0.77 (CI 95% 0.49–1.22, P = 0.27), and RR = 0.95 (IC 95% 0.74–1.24, P = 0.67). In all cohort studies, the acute toxicities were graduated as mild and self-limited with nausea and fatigue being the most common symptoms. Only one case (1/50) of impairment of kidney function was detected as late toxicity in these studies. Conclusions: This SR and meta-analysis indicate that adjuvant RT dramatically reduces the local recurrence of ACC after surgery. Moreover, the treatment has a low acute and late toxicity, resulting in a high therapeutic index. Further, prospective studies are needed to confirm or refute the role of RT on survival and disease recurrence.

Single institution experience treating adrenal metastases with stereotactic body radiation therapy Mira Mahendra Shah, Derek Isrow, Muhammad M Fareed, Ning Wen, Samuel Ryu, Munther Ajlouni, Farzan Siddiqui Journal of Cancer Research and Therapeutics 2019 15(8):27-32 Objective: The objective of the study is to present our experience of treating adrenal metastases using stereotactic body radiation therapy (SBRT). Materials and Methods: We retrospectively reviewed patients with adrenal metastases treated using SBRT from 2001 to 2014. Response Evaluation Criteria in Solid Tumors v1.1 was used. Maximum tumor response was defined as the greatest percentage tumor reduction noted on two or more post-SBRT CT scans. Results: We identified 44 patients (median age 61.3 years, range: 25.8–85), with 54 adrenal metastases; primary diagnoses include non-small cell lung cancer (28 patients and 38 lesions), small cell lung cancer (1 patient), hepatocellular carcinoma (6 patients), and other (9 patients). Treatment was delivered in single (16 lesions, median dose 18 Gy [14–18]) or multiple fractions (38 lesions, median dose 30 Gy [16–40]). Median planning target volume was 49.65cc (3.21–984.54). Median response at first post-SBRT follow-up (median 1.65 months (m) (0.33–5.37), n = 46 lesions) was 10.8% with 91.3% local control. Median maximum tumor response was 31.8% (n = 32 lesions) at median follow-up of 5.4 m (0.9–44.8) with 96.6% local control. The response was comparable regardless of tumor histology or treatment fractionation. No patients experienced Grade 3/4 acute toxicities. One patient with a history of naproxen use required suturing with omental patch placement for perforated pyloric ulcer 14 m post-SBRT (18 Gy in single fraction) to the right adrenal metastasis; this region received <5 Gy. Ten patients treated for pain with available follow-up obtained relief. Conclusions: SBRT is a safe and efficacious treatment for adrenal metastases, demonstrating local tumor control. Further study of the impact on survival and quality of life is warranted.

Comparison of biological-based and dose volume-based intensity-modulated radiotherapy plans generated using the same treatment planning system K Senthilkumar, KJ Maria Das Journal of Cancer Research and Therapeutics 2019 15(8):33-38 Purpose: Nowadays, most of the radiotherapy (RT) treatment planning systems (TPSs) uses dose or dose-volume (DV)-based cost functions for Intensity modulated radiation therapy (IMRT) fluence optimization. Recently, some of the TPSs incorporated biological-based cost function for IMRT optimization. Most of the previous studies compared IMRT plans optimized using biological-based and DV-based cost functions in two different TPSs. Hence, the purpose of the study is to compare equivalent uniform dose (EUD)-based and DV-based IMRT plans generated using the same TPS. Materials and Methods: Twenty patients with prostate cancer were retrospectively selected for this study. For each patient, two IMRT plans were generated using EUD-based cost function (EUD_TP) and DV-based cost (DV_Treatment Plan (TP)), respectively. The generated IMRT plans were evaluated using both physical and biological dose evaluation indices. Results: Biological-based plans ended up with a highly inhomogeneous target dose when compared to DV-based plans. For serial organs, Dnear-max or D2%(Gy) of EUD-based plans showed significant difference with DV-based plans (P = 0.003). For both rectum and bladder, there was a significant difference in mean dose and D30%(Gy) dose between EUD-based plans and DV-based plans. Conclusion: In this study, we decoupled the influence of optimization parameters from the potential use of EUD-based cost functions on plan quality by generating both plans in the same TPS.

Role of serum prostate-specific antigen as predictor for bone metastases in newly diagnosed prostate cancer OP Singh, Veenita Yogi, Pallavi Redhu, HU Ghori, Ananya Pareek, Nancy Lal Journal of Cancer Research and Therapeutics 2019 15(8):39-41 Introduction: Prostate cancer is most frequently diagnosed cancer of men and bone is the most common site of metastasis. There is a lack of consensus for the selection criteria for bone scan in low-risk patients. Western guidelines do not recommend use of bone scan in asymptomatic patients and in low prostate-specific antigen (PSA) values. We try to correlate the PSA value with bone metastases through bone scan in the Indian population. Materials and Methods: A total of 68 histologically newly diagnosed prostate cancer subjected to bone scan were retrospectively analyzed. The patients were stratified into four groups according to their PSA level: The first group of patients had PSA level ranging from 0 to 10 ng/ml (n = 4), the second group had PSA level ranging from 10.1 to 20 ng/ml (n = 13), the third group had PSA levels 20.1–100 ng/ml (n = 23), and the fourth group has PSA >100 (n = 28). Results: The incidence of osseous metastases proven by bone scan was found to be zero (0 out of 4) for PSA level 0–10 ng/ml; 38.46% (5 out of 13) for PSA level 10.1–20, 60.87% (14 out of 23) for PSA level 20.1–100 ng/ml, and 100% for PSA >100 (P < 0.005) (95% confidence interval 1.01–1.1). For cut-off value of PSA ≤10 ng/ml, sensitivity and specificity were 100% and 19.05%, respectively, with positive predictive value of 73.44%. Conclusion: The correlation between PSA value and presence of metastases confirms the usefulness of bone scan scintigraphy in prostate cancer staging. The screening bone scan at initial diagnosis should be included for all patients with PSA >10 ng/ml in Indian setting.

Effect of Au-197 nanoparticles along with Sm-153 radiopharmaceutical in prostate cancer from simulation method Akbar Abbasi, Fahreddin Sadikoglu, Mostafa Hassanzadeh Journal of Cancer Research and Therapeutics 2019 15(8):42-46 Aims: Based on recent studies, it was indicated that gold (Au-197) nanoparticles could be safely prescribed and used to enhance the absorbed dose during radiation therapy. Subjects and Methods: We evaluated the samarium-153 (Sm-153) radiopharmaceutical and Au-197 and Sm-153 radiopharmaceutical absorbed dose rate by means of the Monte Carlo technique in prostate cancer. Results: The results show that absorbed dose rate in entire prostate volume due to 20 mCi of Sm-153 radiopharmaceutical is 27.339 μGy/s, 48.837 μGy/s, and 76.176 μGy/s for γ-interaction, β¯ particle interaction, and γ+β¯ interaction, respectively. The results in the exterior of the prostate for β¯ interaction, β¯ particle interaction, and γ+β¯ interaction were 20.971 μGy/s, 1.110 μGy/s, and 22.081 μGy/s, respectively. Conclusions: The calculation results for Au-197 and Sm-153 radiopharmaceutical show that the absorbed dose rate in entire prostate volume 3% was increased and undesirable dose value in exterior of prostate 7% was decreased.

The effect of metabolic syndrome on prostate cancer final pathology Selahattin Caliskan, Selçuk Kaba, Emrah Özsoy, Muzaffer Oğuz Keleş, Orhan Koca, Mehmet Akyüz, Muhammet Ihsan Karaman Journal of Cancer Research and Therapeutics 2019 15(8):47-50 Aim of Study: Metabolic syndrome (MetS) is an abnormality that increases the risk of cardiovascular disease and diabetes. In the recent years, studies showed that MetS is associated with increased risk of incidence, aggressiveness, and mortality of prostate cancer (PCa). We examined the influence of MetS at final pathology in Turkish patients with PCa. Materials and Methods: MetS was defined according to the American Heart Association, National Heart, Lung, Blood Institute, and International Diabetes Federation and requires any three of five components. The patients without and with MetS were in Group 1 and 2, respectively. Data were compared with independent sample t-test and Chi-squared test. Results: There were 117 patients in the study. The patients' age was between 51 and 77 years with a median of 64.87 ± 5.65 and 62.29 ± 5.57, and prostate-specific antigen (PSA) level of the patients was 8.19 ± 5.35 and 8.68 ± 2.22 ng/ml in Group 1 and 2. Of these patients; Group 1 and 2 had 86 and 31 patients. High-grade PCa (Gleason >7) and advanced PCa (T3, T4) at final pathology were reported in 44.18–18.60% and 38.70–32.25% in Group 1 and 2. Conclusion: The patients with MetS are diagnosed significantly younger and had higher PSA levels than the other patients. Advanced disease of PCa is seen much more in patients with MetS.

Modified U-Shaped ileal neobladder designed for facilitating neobladder-urethral anastomosis in extracorporeal reconstruction after robotic-assisted radical cystectomy Su-Wei Hu, Chia-Chang Wu, Kuan-Chou Chen, Chen-Hsun Ho Journal of Cancer Research and Therapeutics 2019 15(8):51-55 Background/Objective: To report the initial experience and the early outcomes of a modified U-shaped ileal neobladder, which was developed to facilitate the neobladder-urethral anastomosis by minimizing the anastomotic tension. Patients and Methods: Between June 2015 and December 2016, two male and two female patients (median age: 65.5 years, range: 43–72 years) underwent the modified U-shaped ileal neobladder after robotic-assisted radical cystectomy (RARC). The most mobile and dependent ileal segment was first selected intracorporeally as the site for later neobladder-urethral anastomosis. The neobladder was formed extracorporeally, and the previously selected ileal segment formed the most dependent portion of the neobladder. The neobladder-urethral anastomosis was completed after robotic redocking. Results: The median follow-up was 8 months (3–21 months). The median operative time, console time, and extracorporeal reconstruction time were 620 min (534–674 min), 372 min (314–420 min), and 151 min (128–215 min), respectively. In all patients, the neobladder-urethral anastomosis was completed intracorporeally with minimal tension. The median hospital time after the surgery was 14.5 days (14–19 days). Postoperatively, the median peak flow rate and void volume were 10 ml/s (4–35 ml/s) and 258 ml (88–775 ml). The median postvoid residual was 20 ml (10–53 ml). At daytime, two were completely continent; the other two reported mild (1–2 pads) and moderate (>2 pads) incontinence at the postoperative 3 and 4 months, respectively. Three reported nocturnal enuresis. Conclusions: Our initial experience demonstrated that the modified U-shaped neobladder designed for minimizing the anastomotic tension is safe and feasible with its satisfactory functional outcomes.

A prospective study to compare the measured glomerular filtration rate compared to estimated glomerular filtration rate in patients undergoing definitive chemoradiation, with platinum agents for various malignancies A.H Rudresh, Vikas Asati, K.C Lakshmaiah, D Lokanatha, Suresh Babu, L.K Rajeev, K.N Lokesh, Govind Babu Journal of Cancer Research and Therapeutics 2019 15(8):56-59 Context: Renal function assessment is of paramount importance before using the platinum agents especially cisplatin. Glomerular filtration rate (GFR) estimation by diethyl-triamine-penta-acetic acid (DTPA) scan (measured GFR [mGFR]) is considered gold standard. Aims: The aim of this study is to know if we can replace the mGFR with the GFR estimation with Cockcroft–Gault formula (eGFR) in patients undergoing chemoradiation. Settings and Design: This is a prospective, descriptive study. Subjects and Methods: Patients who are planned for definitive chemoradiation will be eligible for the study. Renal function will be measured DTPA scan and Cockcroft–Gault (CG) formula. Subgroup analysis based on the weight, age, and sex will be done. Statistical Analysis Used: Demographic and renal function parameters were analyzed using summary measures. To test the significance of the difference between mGFR and cGFR, a paired t-test will be used; to look for an association between various estimates of renal function, the Pearson's correlation coefficient will be calculated using a two-tailed test. Results: Median mGFR of patients was 82.7 (range: 65–125 ml/min, standard deviation [SD] =14.0 ml/min) while the median eGFR as per the CG formula was 83.9 ml/min (range: 37–137 ml/min, SD = 24.4 ml/min). The median mGFR was only 1.2 ml/min lesser when measures by the CG formula with no significance difference between them (P = 0.66, 95% confidence interval: −4.5–6.3). Conclusions: We concluded that in resource-limited setting eGFR using CG formula can replace mGFR, especially in patients with age <60 years. Although weight did not showed a significant difference by two methods, a study with large sample is needed to confirm the result.