Oral Oncology

Patient access to voice prostheses and heat and moisture exchangers: Factors influencing physician's prescription and reimbursement in eight European countries Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): A.C.C. Beck, V.P. Retèl, M.W.M. van den Brekel, W.H. van Harten Abstract Objectives Patient access to the voice prosthesis and heat and moisture exchanger (HME) is not always guaranteed in Europe. Therefore, the aim of this qualitative study is to evaluate factors influencing physician's prescription and reimbursement of these devices in eight European countries, and to identify barriers of and facilitators to effective patient access. Materials and methods In this mixed methods study, we conducted a survey among stakeholders evaluating prescription (Part 1 of the survey), reimbursement (Part 2), and barriers of and facilitators to effective patient access (Part 3). Part 1 was completed by head and neck surgeons employed in France, Germany, the United Kingdom, Italy, Spain, Belgium, the Netherlands and Poland. Part 2 and 3 were completed by medical device company representatives in respective countries, followed by semi-structured interviews. Results Based on the survey, filled in by 36 surgeons, all prescribed the voice prosthesis. Four surgeons didn't prescribe the HME in Italy and Poland due to lack of both reimbursement and experience/training, and feeling uncomfortable with device use. Most restrictive factors (e.g. increased workload, insufficient staff) occurred in countries with decentralized healthcare systems including Spain and Italy. Conclusion Non-HME-usage was influenced by economical and physician-related factors. Restrictive factors were related to limited regional device reimbursement and provision. Nationwide reimbursement, guideline implementation, support for physicians by training/education and providing a rehabilitation team will increase device use.

Results of a combination treatment with intensity modulated radiotherapy and active raster-scanning carbon ion boost for adenoid cystic carcinoma of the minor salivary glands of the nasopharynx Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Sati Akbaba, Dina Ahmed, Kristin Lang, Thomas Held, Matthias Mattke, Juliane Hoerner-Rieber, Klaus Herfarth, Stefan Rieken, Peter Plinkert, Juergen Debus, Sebastian Adeberg Abstract Objectives We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. Materials and methods We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. Results The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. Conclusion Bimodal RT including active raster-scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.

Quality insurance in head and neck cancer multidisciplinary team meetings: A watchful eye on real-life experience Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Jean-Baptiste Guy, Marouan Benna, Yaoxiong Xia, Elisabteh Daguenet, Majed Ben Mrad, Omar Jmour, Nicolas Vial, Yann Lelonge, Pierre Fournel, Jean-Michel Prades, Alexis Vallard, Nicolas Magné Abstract Introduction Although Multidisciplinary Team Management (MDT) is integrated in most international head and neck cancer treatment guidelines, its applications and proceedings were rarely described. The present study explores a 6-year real-life experience in a French Comprehensive Cancer Care Center. Methods Patients, tumor and meeting characteristics of all consecutive cases discussed in head and neck MDT meetings between 2010 and 2015 were retrospectively reviewed. Results From 2010 to 2015, 1849 cases (accounting for 1786 patients) were discussed in 138 MDT meetings. Median age was 62 (range: 15–96). When reported (n = 310, 16.8%), performance status was ≥2 in 36.1% of patients. Tumors were mainly squamous cell carcinomas (n = 1664, 91.5%) of the larynx/hypo-pharynx (n = 630, 34.4%), oropharynx (n = 518; 28.3%) and oral cavity (n = 339; 18.5%). Tumors were diagnosed at a locally (n = 358, 25%), locally advanced (n = 946, 66%) or metastatic setting (n = 53, 3.7%). Mean number of discussed patients per MDT meeting was 16 (range: 3–32). Most patients were discussed once (n = 1663, 97%). Most patients (n = 969, 52%) underwent treatment before MDT meetings: mainly surgery (n = 709, 73.2%). The mean time between MDT meeting and first radiation course was 21 days (range: 1–116). Discussion Optimal multimodal treatment management is based on MDT meetings and results from the interaction and coordination of surgeons, medical and radiation oncologists. In the present series, most patients were discussed once despite the number of expected recurrences, suggesting that the management of tumor progression was not discussed in head and neck MDT meetings. Furthermore, most patients had surgery before MDT meeting, pointing out that MDT role and place still needs to be improved. Finally, the present population significantly differed from patients included in phase III clinical trials, with more advanced age and poorer condition. It calls for the necessity of a high-quality head and neck MDT meeting since evidence-based recommendations should be adapted to patient's frailties.

Time trends of thyroglobulin antibody in ablated papillary thyroid carcinoma patients: Can we predict the rate of negative conversion? Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Eyun Song, Jonghwa Ahn, Hye-Seon Oh, Min Ji Jeon, Won Gu Kim, Won Bae Kim, Young Kee Shong, Jung Hwan Baek, Jeong Hyun Lee, Jin Sook Ryu, Ki Wook Chung, Suck Joon Hong, Tae Yong Kim Abstract Objectives Persistence of thyroglobulin antibody (TgAb) in patients with papillary thyroid carcinoma (PTC) years after total thyroidectomy (TT) followed by ablation occurs even without any evidence of structural disease. Few studies have studied the natural course of TgAb positivity and factors that may influence this course. The present study evaluated the time trends of TgAb in ablated PTC patients and aimed to identify the predictive factors for the rate of negative conversion of TgAb. Materials and methods Overall, 1279 patients who underwent TT and subsequent ablation for PTC, with available data on thyroid peroxidase Ab (TPOAb) and TgAb prior to surgery (preop-) and ablation (abl-) were enrolled. Patients with initial distant metastasis or recurrence during follow-up were excluded. Results and conclusion Preop-TgAb was positive in 24.9% of patients (n = 319), whereas abl-TgAb positivity decreased to 12.8% (n = 164). In 164 patients positive for abl-TgAb, TgAb in patients with higher abl-TgAb levels decreased more gradually than those observed in patients with lower abl-TgAb levels (p < 0.001). Furthermore, in patients within the same range of abl-TgAb levels, patients positive for abl-TPOAb had a higher rate of negative conversion of TgAb compared with negative patients for abl-TPOAb (log rank p < 0.001). TPOAb significantly increased the rate of negative conversion in multivariate analysis adjusted for abl-TgAb (odds ratio 1.59, 95% confidence interval 1.11–2.28, p = 0.011). This study clearly showed that abl-TgAb titers and abl-TPOAb status can predict the rate of negative conversion. These findings can guide the optimal timing for additional examination in patients positive for TgAb during follow-up.

Differences of tumor-recruiting myeloid cells in murine squamous cell carcinoma influence the efficacy of immunotherapy combined with a TLR7 agonist and PD-L1 blockade Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Hidetake Tachinami, Naoto Nishii, Yulong Xia, Yoshihisa Kashima, Tatsukuni Ohno, Shigenori Nagai, Lixin Li, Walter Lau, Kei Tomihara, Makoto Noguchi, Miyuki Azuma Abstract Objectives The immune status of the tumor microenvironment has a marked impact on clinical outcomes. Here we examined the immune environments of tumor-infiltrating leukocytes (TILes) in two murine models of squamous cell carcinoma and compared the effects of immunotherapeutic agents, including a TLR7 agonist and an immune checkpoint inhibitor, and a chemotherapeutic agent, gemcitabine, in these models. Materials and methods TILes from NR-S1- and SCCVII-grafted mice were analyzed by flow cytometry. NR-S1-inoculated mice received resiquimod (a synthetic TLR7 agonist), an anti-PD-L1 antibody, or both, and tumor growth and TILs were examined. Gemcitabine was administered to deplete CD11b+ cells. Results More than 50% of TILes from NR-S1- and SCCVII-inoculated mice were CD11b+Gr-1+ cells. A major fraction of NR-S1 CD11b+ cells was Ly6GhighLy6Clow-negaF4/80− tumor-associated neutrophils (TANs) and the majority of SCCVII CD11b+ cells were Ly6GlowLy6C−F4/80+ tumor-associated macrophages. NR-S1 TANs did not express MHC class II and CD86, but did express reactive oxygen species and PD-L1. Resiquimod, alone and in combination with an anti-PD-L1 antibody, did not regress NR-S1 tumors, but the combination increased the CD8/regulatory T cell-ratio, and IFN-γ and PD-1 expression in CD8+ TILes. Pre-administration of low-dose gemcitabine prior to the combination treatment suppressed the progression of NR-S1 tumors. Conclusions NR-S1 tumors with abundant recruitment of TANs were resistant to treatments with a TLR7 agonist, alone and in combination with PD-1 blockade, and required an additional gemcitabine treatment. The phenotype and status of tumor-infiltrating CD11b+ myeloid cells may influence the efficacy of immunotherapeutic agents.

Patient-reported outcomes of symptom burden in patients receiving surgical or nonsurgical treatment for low-intermediate risk oropharyngeal squamous cell carcinoma: A comparative analysis of a prospective registry Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Moran Amit, Kate Hutcheson, Jhankruti Zaveri, Jan Lewin, Michael E Kupferman, Amy C Hessel, Ryan P Goepfert, G. Brandon Gunn, Adam S Garden, Renata Ferraratto, C. Dave Fuller, Samantha Tam, Neil D. Gross Abstract Purpose To explore treatment-related changes in symptom burden and quality of life (QOL) in oropharyngeal squamous cell cancer (OPSCC) patients treated surgically and non-surgically. Patients and Methods Eighty-six patients with human papillomavirus–associated OPSCC treated at the Head and Neck Center at The University of Texas MD Anderson Cancer Center were recruited to a prospective registry study between 2014 and 2016 and completed the core, head and neck-specific, and symptom interference sections of the MD Anderson symptom inventory (MDASI) multi-symptom questionnaire and the EQ-5D health status assessment as a measure of QOL at four time points. Results Longitudinal improvements from post-treatment nadir were observed across all groups. For patients treated with single modality, symptom interference, but not core and head and neck specific, MDASI scores were significantly better at 6 months in patients treated with surgery than radiation (P = 0.04). For patients treated with multiple modalities, scores for each of the three domains (i.e., core, head and neck -specific, and interference MDASI) were significantly better in the surgical group than the nonsurgical group at treatment completion (P = 0.0003, P = 0.0006 and P = 0.02) and 6 weeks (P = 0.001, P = 0.05 and P = 0.04), but not 6 months (P = 0.11, P = 0.16 and P = 0.040). No significant differences in EQ5D health status were observed between groups at any time point, reflecting similar overall QOL in all groups. Conclusion Symptom burden and QOL improves after treatment in OPSCC survivors over time regardless of whether primary surgical or nonsurgical treatment is used, although acute symptom profiles may differ.

Patterns of EBV-positive cervical lymph node involvement in head and neck cancer and implications for the management of nasopharyngeal carcinoma T0 classification Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Wei-Jie Luo, Yan-Fen Feng, Rui Guo, Ling-Long Tang, Lei Chen, Guan-Qun Zhou, Wen-Fei Li, Xu Liu, Ying Sun, Ai-Hua Lin, Jun Ma, Yan-Ping Mao Abstract Objectives Epstein-Barr virus (EBV)-positive cervical lymph node (CLN) metastasis of unknown primary origin is classified as nasopharyngeal carcinoma (NPC) T0 by the American Joint Committee on Cancer staging manual (8th edition). We aimed to investigate the possible primary sites and patterns of EBV-positive CLN metastases and to provide implications for the management of NPC T0 classification. Materials and methods We retrospectively reviewed 269 patients with newly diagnosed EBV-positive CLN metastatic disease who underwent EBV detection via EBV-encoded RNA in situ hybridization. Fifteen patients with unknown primary tumors underwent follow-up after initial treatment. Results In patients with EBV-positive CLNs, the most common primary sites after the nasopharynx (51.7%) were the salivary gland (24.5%), lung (7.8%), oropharynx (3.3%), nasal cavity/maxillary (3.3%), oral cavity (2.2%), orbit (1.1%), and liver (0.4%). No primary site was found in 15 patients (5.6%). For salivary gland malignancies, level II and I were the most frequently involved regions. Tumors arising from the lung or liver metastasized to the lower neck (level IV, V, and VI) rather than the upper neck. After initial treatment, 2/15 patients with EBV-positive CLNs of unknown primary exhibited primary NPC and oropharyngeal tumor, respectively. Further, even without prophylactic irradiation to the nasopharynx, only one of 13 unknown primary patients developed NPC. Conclusions The origins of EBV-positive CLNs may not be restricted to the nasopharynx alone, and are likely to involve the head and neck or non-head and neck regions. NPC T0 classification should be cautiously assigned to such tumors.

Human papillomavirus detection in matched oral rinses, oropharyngeal and oral brushings of cancer-free high-risk individuals Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Maria Gabriella Donà, Barbara Pichi, Francesca Rollo, Maria Benevolo, Alessandra Latini, Valentina Laquintana, Raul Pellini, Manuela Colafigli, Mirko Frasca, Massimo Giuliani, Antonio Cristaudo Abstract Objectives The detection of oral Human Papillomavirus (HPV) may be of clinical utility because of the major role HPV plays in the etiology of oropharyngeal cancer. However, oral HPV testing is not standardized and the best sampling method has yet to be identified. We aimed to compare HPV findings in matched oral rinse-and-gargles (rinses), oropharyngeal brushings and oral brushings. Materials and methods HPV-DNA was investigated using Linear Array in samples collected from cancer-free individuals at increased risk for oral HPV. Results 163 oral rinses already tested for HPV were selected. The matched oropharyngeal (n = 163) and oral brushings (n = 100) were analyzed. The detection rate for any HPV, high-risk (HR)-HPVs and HPV16 was significantly higher in rinses than brushings. The overall agreement for any HPV between rinses and oropharyngeal brushings was 51.2% (Cohen K: 0.14, 95% CI: 0.07–0.21). The proportion of positive agreement was 16.8%. The overall agreement for HR-HPVs was 74.1% (Cohen K: 0.20, 95% CI: 0.07–0.33). The genotype-specific profile of rinses and brushings which were concomitantly HPV-positive only partially overlapped in cases with multiple infections, with more genotypes detected in the rinse, which were not isolated in the corresponding brushings. Conclusion The agreement for HPV status between rinses and brushings is poor, particularly for the HPV-positive findings. Despite the fact that the origin of the HPV-infected cells present in the oral rinse is unclear, since they could not be traced back to the oropharynx or oral cavity, oral rinses provided the highest detection rate for HR-HPVs and HPV16.

The prognosis of head and neck squamous cell carcinoma related to immunosuppressive tumor microenvironment regulated by IL-6 signaling Publication date: April 2019 Source: Oral Oncology, Volume 91 Author(s): Ming-Shao Tsai, Wen-Cheng Chen, Chang-Hsien Lu, Miao-Fen Chen Abstract Evasion of immune surveillance is a significant factor in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. IL-6 signaling is a critical mechanism for the induction of dysfunctional immune responses. In the present study, we examined the role of IL-6 in the prognosis of HNSCC regarding the immunosuppressive tumor microenvironment. We retrospectively analyzed the clinical outcomes of HNSCC patients and examined its correlation with the levels of IL-6 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in peripheral blood. Furthermore, the relationships between IL and 6, programmed death ligand (PD-L1) expression, and immune response were examined in vitro and in vivo. Our data revealed that IL-6 overexpression was associated with the increased risk of developing disease failure and poor prognosis for HNSCC. The immunoreactivity of IL-6 in HNSCC specimens was positively linked to the staining of PD-L1 and the level of circulating MDSCs. By cellular and animal experiments, there were augmented radiation-induced increases in the expression of PD-L1 and the activation of MDSCs noted in IL-6-positive tumors. When IL-6 signaling was inhibited, the levels of PD-L1 and MDSC recruitment were significantly down-regulated. Furthermore, the neutrophil-to-lymphocyte ratio (NLR) was positively correlated with the levels of IL-6 and PD-L1 in tumor, and circulating MDSCs. In conclusion, IL-6 is a significant predictor of treatment outcome in HNSCC patients, and plays an important role in the induction of immunosuppressive tumor microenvironment mediated by increased MDSCs and PD-L1 expression. Furthermore, IL-6 combined with NLR can assist the clinician to make an informed decision regarding treatment options.

Organ preservation in laryngeal and hypopharyngeal cancer Publication date: March 2019 Source: Oral Oncology, Volume 90 Author(s): Stephen Kang