Somatic 9p24.1 alterations in HPV- head and neck squamous cancer dictate immune microenvironment and anti-PD-1 checkpoint inhibitor activity.

Somatic copy number alterations (SCNAs), generally (1) losses containing interferons and interferon-pathway genes, many on chromosome 9p, predict immune-cold, immune checkpoint therapy (ICT)-resistant tumors (2); however, genomic regions mediating these effects are unclear and probably tissue specific. Previously, 9p21.3 loss was found to be an early genetic driver of human papillomavirus-negative (HPV-) head and neck squamous cancer (HNSC), associated with an immune-cold tumor microenvironment (TME) signal, and recent evidence suggested that this TME-cold phenotype was greatly enhanced with 9p21 deletion size, notably encompassing band 9p24.1 (3). Here, we report multi-omic, -threshold and continuous-variable dissection of 9p21 and 9p24 loci (including depth and degree of somatic alteration of each band at each locus, and each gene at each band) and TME of four HPV- HNSC cohorts. Preferential 9p24 deletion, CD8 T-cell immune-cold associations were observed, driven by 9p24.1 loss, and in turn by an essential telomeric regulatory gene element, JAK2-CD274. Surprisingly, same genetic region gains were immune hot. Related 9p21-TME analyses were less evident. Inherent 9p-band-level influences on anti-PD1 ICT survival rates, coincident with TME patterns, were also observed. At a 9p24.1 whole-transcriptome expression threshold of 60th percentile, ICT survival rate exceeded that of lower expression percentiles and of chemotherapy; below this transcript threshold, ICT survival was inferior to chemotherapy, the latter unaffected by 9p24.1 expression level (P-values < 0.01, including in a PD-L1 immunohistochemistry-positive patient subgroup). Whole-exome analyses of 10 solid-tumor types suggest that these 9p-related ICT findings could be relevant to squamous cancers, in which 9p24.1 gain/immune-hot associations exist.

A comparative dose-escalation analysis for reirradiated cancer patients with and without appropriate dose mapping.

This study aims to compare dose escalation between two groups of reirradiated cancer patients, one with the previous contour and radiotherapy plan available on the treatment planning system and the other without. First group is identified as DICOM-group, while the other one is called non-DICOM group. The current study included 89 patients, 57 in the DICOM, and 32 in the non-DICOM group, who received reirradiation for recurrent or second primary tumours between 2019 and 2021. For the DICOM group, doses to 0.2cc volume for spine, brainstem, and optic apparatus from first radiation were converted into structures and transferred to reirradiation CT using deformable registration. First, one radiotherapy plan was created using the doctor prescribed dose (baseline prescription RxD_B); further an escalated dose (RxD_E) plan, taking into account all the dose volume parameters from previous radiation, was created only for DICOM group. In non-DICOM group patients were planned only for RxD_B. The maximum accepted dose escalation was 21 Gy. Radiotherapy prescription dose during earlier (first) treatment in DICOM and non-DICOM groups were 61 ± 5.6 Gy and 30-66 Gy, respectively. DICOM and non-DICOM groups had nearly identical baseline doses: 52.5 ± 10.7 Gy and 50.6 ± 6.9 Gy (difference 1.9 ± 12.7 Gy). Dose escalation was possible for 51 out of 57 patients in the DICOM-group. Average escalated dose in DICOM-group was 59.2 ± 6.2 Gy, with an incremental dose of 6.7 ± 12.4 Gy from the baseline prescription. No dose escalation was opted for in the non-DICOM group due to the unavailability of dose volume information from previous radiation. Reirradiation for head and neck cases allowed for a moderate to high dose escalation, facilitated by the presence of pertinent DICOM information from the initial radiotherapy.

External validation of an 18F-FDG-PET radiomic model predicting survival after radiotherapy for oropharyngeal cancer.

PURPOSE/OBJECTIVE: The purpose of the study is to externally validate published 18F-FDG-PET radiomic models for outcome prediction in patients with oropharyngeal cancer treated with chemoradiotherapy. MATERIAL/METHODS: Outcome data and pre-radiotherapy PET images of 100 oropharyngeal cancer patients (stage IV:78) treated with concomitant chemotherapy to 66-69 Gy/30 fr were available. Tumors were segmented using a previously validated semi-automatic method; 450 radiomic features (RF) were extracted according to IBSI (Image Biomarker Standardization Initiative) guidelines. Only one model for cancer-specific survival (CSS) prediction was suitable to be independently tested, according to our criteria. This model, in addition to HPV status, SUVmean and SUVmax, included two independent meta-factors (Fi), resulting from combining selected RF clusters. In a subgroup of 66 patients with complete HPV information, the global risk score R was computed considering the original coefficients and was tested by Cox regression as predictive of CSS. Independently, only the radiomic risk score RF derived from Fi was tested on the same subgroup to learn about the radiomics contribution to the model. The metabolic tumor volume (MTV) was also tested as a single predictor and its prediction performances were compared to the global and radiomic models. Finally, the validation of MTV and the radiomic score RF were also tested on the entire dataset. RESULTS: Regarding the analysis of the subgroup with HPV information, with a median follow-up of 41.6 months, seven patients died due to cancer. R was confirmed to be associated to CSS (p value = 0.05) with a C-index equal 0.75 (95% CI=0.62-0.85). The best cut-off value (equal to 0.15) showed high ability in patient stratification (p=0.01, HR=7.4, 95% CI=1.6-11.4). The 5-year CSS for R were 97% (95% CI: 93-100%) vs 74% (56-92%) for low- and high-risk groups, respectively. RF and MTV alone were also significantly associated to CSS for the subgroup with an almost identical C-index. According to best cut-off value (RF>0.12 and MTV>15.5cc), the 5-year CSS were 96% (95% CI: 89-100%) vs 65% (36-94%) and 97% (95% CI: 88-100%) vs 77% (58-93%) for RF and MTV, respectively. Results regarding RF and MTV were confirmed in the overall group. CONCLUSION: A previously published PET radiomic model for CSS prediction was independently validated. Performances of the model were similar to the ones of using only the MTV, without improvement of prediction accuracy.

Mapping the impact of malnutrition as defined by the Global Leadership Initiative on Malnutrition and nutrition impact symptoms on the possibility of returning to work after treatment for head and neck cancer.

PURPOSE: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer. METHODS: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1-5) at each follow-up using the Head and Neck Patient Symptom Checklist© (HNSC©). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work. RESULTS: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years. CONCLUSION: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC© at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03343236 (date of registration 17/11/2017).

Assessment of Dimensional Changes in Submandibular Glands in Head-Neck Radiotherapy Patients by Ultrasonography.

OBJECTIVES: The present study investigated the dimensional changes in the submandibular glands following radiotherapy using ultrasonography. METHODS: Twenty-three patients planned to receive head-neck radiotherapy were included in this study. The anteroposterior, superoinferior, mediolateral length, and volumes of 46 submandibular glands were measured by ultrasonography at 3 different time periods (before radiotherapy and in the second and sixth months after the radiotherapy onset) and evaluated in terms of dimensional changes and the effect of the radiation dose on these changes. The data were statistically analyzed using repeated measures analysis of variance (ANOVA) and 2-factor repeated measures ANOVA. RESULTS: Before radiotherapy and in the second and sixth months after the radiotherapy onset, mean anteroposterior length of the submandibular glands was 32.39 ± 4.55, 30.38 ± 4.80, and 31.50 ± 3.68 mm, respectively; mean superoinferior length was 9.96 ± 1.54, 8.76 ± 1.26, and 9.08 ± 1.01 mm, respectively; mean mediolateral length was 24.66 ± 3.77, 22.03 ± 3.73, and 21.76 ± 4.01 mm, respectively; and mean volume was 4.21 ± 1.01, 3.08 ± 0.77, and 3.32 ± 0.63 cm3 , respectively. Moreover, there were significant differences in the anteroposterior (P < .01), superoinferior (P < .001), and mediolateral lengths (P < .001), as well as the volumes (P < .001) of the submandibular glands measured at the 3 different time periods. CONCLUSION: In the second and sixth months after the radiotherapy onset, the sizes of the submandibular glands were markedly reduced, but it partially recovered to normal as more time elapsed after radiotherapy.

Prognostic significance of extra-nodal extension and positive surgical margins in HPV positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Whether extra-nodal extension (ENE+) and surgical margin positivity (margin+) are poor prognostic factors in HPV-associated (HPV+) oropharyngeal carcinoma (OPC) remains uncertain. RESULTS: Our study evaluated if microscopic ENE+ and/or margin+ are associated poorer recurrence free survival (RFS) and overall survival (OS) in HPV+ OPC. Patients were classified as high risk (ENE+ and/or margin+) or low risk (ENE- and margins-). Of a total of 176 patients HPV+ OPC, 81 underwent primary surgery and dad data on ENE and margin status. There was no statistically significant difference in RFS (p = 0.35) or OS (p = 0.13) for high-risk versus low-risk groups. Ongoing smoking (p = 0.023), alcohol use (p = 0.044) and advanced stage (p = 0.019) were associated with higher risk of recurrence. Only advanced stage (p-value <0.0001) was associated poorer overall survival. CONCLUSIONS: The presence of ENE+ and/or margin+ was not an independent predictor of poor RFS or OS in HPV+ OPC.

Association between tooth extraction during radiotherapy and the risk of osteoradionecrosis in patients with head and neck cancers.

PURPOSE: It is commonly recommended that tooth extraction should be performed prior to radiotherapy (RT) in patients with head neck cancer to prevent osteoradionecrosis (ORN). However, doctors still occasionally encounter patients who require tooth extraction during RT. This study aimed to determine the risk of ORN in patients who undergo tooth extraction during RT. METHODS: Data were collected from Taiwan's National Health Insurance Research Database. We retrospectively enrolled 24,412 patients with head and neck cancer treated with radiotherapy between 2011 and 2017. The associations between ORN and demographic characteristics, timing of tooth extraction, and treatments were examined using univariate and multivariable Cox proportional hazards regression models. RESULTS: A total of 24,412 head and neck cancer patients were enrolled; 133 patients underwent tooth extraction during RT and 24,279 patients did not undergo tooth extraction during RT. Tooth extraction during RT was not associated with a significantly higher risk of ORN (hazard ratio [HR] = 1.303, P = 0.4862). Tumor site, RT dose ≥ 60 Gy, age < 55 y/o, mandibulectomy, chronic periodontitis, and chemotherapy were significantly associated with a higher risk of ORN. CONCLUSION: The risk of ORN in head and neck cancer is not significantly different between patients who undergo tooth extraction during RT and patients who do not undergo tooth extraction during RT.

Post-therapeutic surveillance of HPV-driven oropharyngeal cancers: are we ready to change our practices?

PURPOSE: Although HPV-positive and negative oropharyngeal cancers are two distinct diseases, Post-Therapeutic Surveillance (PTS) modalities are similar. Adjusting PTS strategies to HPV status will represent a massive practice change that raises the issue of its acceptability, by both physicians and patients. METHODS: Two distinct surveys were designed and submitted, respectively, to HPV-positive patients and physicians (surgeons, radiation and medical oncologists) involved in head and neck cancer treatment. RESULTS: 133 patients and 90 physicians have participated to the study. Most patients were reluctant to embrace new PTS options (remote consultations, nurse consultations and smart phone applications). However, 84% of patients would be favorable to use HPV Circulating DNA (HPV Ct DNA) measurement to guide surveillance modalities. 57% of physicians acknowledged that our current PTS strategy is improvable and most of them would accept the use of new monitoring options from the third year of follow-up. 87% of physicians would be interested to participate to a trial comparing the current PTS strategy to a new approach, where monitoring modalities (number of visits, imaging prescription) would depend on HPV Ct DNA level. CONCLUSIONS: Patients and physicians are aware that PTS modalities should depend on HPV status. Their adhesion is a prerequisite to any potential changes. Strategies based on HPV Ct DNA measurement should be assessed within a randomized clinical trial.

Pignat's vertical partial laryngectomy with crico-hyoido-epiglotto-plasty.

PURPOSE: Pignat's partial laryngectomy with crico-hyoido-epiglotto-plasty (CHEPL) is a vertical laryngectomy with resection of the anterior portion of the thyroid cartilage and reconstruction with a wires net and the subhyoid muscles. The aim of this retrospective study was to evaluate and analyze oncologic and functional outcomes in patients affected by laryngeal squamous cell carcinoma and treated with Pignat's partial laryngectomy. METHODS: Seventy patients with cT1-cT3 glottic cancer were surgically treated with Pignat's technique. EXCLUSION CRITERIA: invasion of posterior cricoid arch, more than 3 mm under glottis, of more than one arytenoid, of posterior portion of thyroid cartilage, of the suprahyoid epiglottis. Overall survival, disease free survival, rates of decannulation and enteral feeding were analyzed. RESULTS: 23 (32.9%) pT1, 37 (52.9%) pT2, 5 (7.1%) pT3, 5 (7.1%) pT4a, 64 (91.5%) pN0, 5 (7.1%) pN1, 1 (1.4%) pN2. Adjuvant treatment was administered to 13 patients (18.6%). All patients had tracheotomy. Five year OS and DFS were 81.66 and 77.95%, respectively. A statistically significant DFS difference was observed between early and late stages. Five year local control was 81.16%. Five year larynx preservation rate was 89.16%. Median decannulation time was 12 days. Median duration of enteral nutrition was 16 days. All patients achieved efficient phonation. CONCLUSION: Pignat's partial laryngectomy with CHEPL can represent an alternative to horizontal supracricoid laryngectomy to achieve laryngeal preservation. Good oncologic and functional outcomes are possible as long as indications are followed.

[Role of Robotic Surgery in ENT]. / Bedeutung der transoralen robotischen Chirurgie in der HNO.

Since the beginning of the 21st century, surgical robots have been used in the ENT-environment. They primarily support surgeons in minimal invasive transoral operations, especially in multidisciplinary treatment concepts of head and neck tumors, but also in snoring surgery the robot provides a complement to the established transoral laser surgery. In the meantime there is a large number of data that deals with the importance of oncological results, function maintenance, economics and future perspectives.Operation areas of the current robot devices are still limited in the ENT-environment. As the number of cases are small, efforts are being made to connect centres on a national and international level. Thus, uniform training standards, targeted knowledge and data exchange as well as further development of systems would be managed better. The creation of small and agile ENT-specific equipment could expand the possibilities as a next step for the future and finally lead to a wide scale of ENT-surgical applications.

A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction.

In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis-Havrda-Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head-neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis-Havrda-Charvat cross-entropy is a parameterized cross-entropy with the parameter α. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy for α=1. The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head-neck cancers and 146 from lung cancers. The results show that Tsallis-Havrda-Charvat entropy can achieve better performance in terms of prediction accuracy with some values of α.

It Takes Two to Tango: Patients' and Providers' Perspectives in Tobacco Cessation and Head/Neck Cancer.

BACKGROUND: Tobacco cessation among patients with head/neck cancer continues to be challenging despite evidence that cessation improves treatment outcomes. The purpose of this study was to understand barriers/facilitators to tobacco cessation among patients with head/neck cancer and health care providers and to obtain perspectives toward the development of a patient-centered tobacco cessation intervention. MATERIALS AND METHODS: In-depth qualitative interviews with 10 health care providers and 21 patients with head/neck cancer (12 inpatients and 9 outpatients) who were current or former smokers. RESULTS: Health was a common motivator to quit among patients. Although most patients indicated that their health care provider asked and advised them to quit, they were unaware of cessation resources. Suggestions for a tobacco cessation program included involvement of former smokers, health care provider involvement/counseling, supporting written materials, and incorporating follow-up and family support. Health care providers identified patients' anger/frustration associated with the disease, social/demographic issues, and poor quality of life as the three most frequent challenges in treating patients. Although all providers reported asking about tobacco use, 70% emphasized a lack of formal training in tobacco cessation and lack of time. Their suggestions for a cessation program included having a "quarterback" responsible for this component with support from the entire health care team and continuity between outpatient and inpatient services to promote cessation, prevent relapse, and highlight the importance of follow-up and social support. CONCLUSION: There is great interest and need, both from patients and providers, for tobacco cessation services in the oncology setting tailored for patients with head/neck cancer in the context of cancer care. IMPLICATIONS FOR PRACTICE: Although the combination of pharmacotherapy and cognitive-behavioral intervention is the standard evidence-based treatment for tobacco dependence, it must be adapted to meet the needs and wants of patients and providers to be effective. This study provides an in-depth examination of such needs among patients with head and neck cancer and providers in the context of cancer care. Providers and patients emphasized the need of having a trained health care provider dedicated to providing tobacco cessation through seamless integration between outpatient and inpatient services as well as follow-up with an emphasis on family involvement throughout the process.

Depression, anxiety, fatigue, and quality of life in a large sample of patients suffering from head and neck cancer in comparison with the general population.

BACKGROUND: Treatment of head and neck cancer (HNC) often leads to visible and severe functional impairments. In addition, patients often suffer from a variety of psychosocial problems, significantly associated with a decreased quality of life. We aimed to compare depression, anxiety, fatigue and quality of life (QoL) between HNC patients and a large sample of the general population in Germany and to examine the impact of sociodemographic, behavioral and clinical factors on these symptoms. METHODS: We assessed data of HNC patients during the aftercare consultation at the Leipzig University Medical Center with a patient reported outcome (PRO) tool named "OncoFunction". Depression, anxiety, fatigue and QoL were assessed using validated outcome measures including the PHQ-9, the GAD-2, and the EORTC QLQ-C30 questionnaire. RESULTS: A total of 817 HNC patients were included in our study and compared to a sample of 5018 individuals of the general German population. HNC patients showed significantly higher levels of impairment in all dimensions assessed. Examination of association between depression, anxiety, fatigue and QoL and clinical as well as sociodemographic variables showed significant relationships between occupational status, ECOG-state, body mass index and time since diagnosis. CONCLUSIONS: HNC patients suffer significantly from psychological distress. The used questionnaires are suitable for the use in daily routine practice and can be helpful to increase the detection of depression, anxiety and fatigue and therefore can improve HNC aftercare.

Risk for COVID-19 infection in patients with tobacco smoke-associated cancers of the upper and lower airway.

PURPOSE: Cancer patients are regarded as a group at risk for both COVID-19 infection and severe clinical course because of advanced age, comorbidities and iatrogenic immune impairment. Among them, patients with cancer of the upper and lower airways share other risk factors, mostly related to tobacco-smoke exposure, including male gender, airway epithelial damages, chronic obstructive respiratory disease (COPD), cardiovascular and cerebrovascular diseases. Clinical and pathophysiological factors shared by these conditions are reviewed. METHODS: Review of the published literature since the beginning of 2020. RESULTS: COVID-19 is a respiratory infectious disease and SARS-CoV-2 replication and shedding occurs in nasal and bronchial epithelial respiratory cells through the interaction with ACE2 and TMPRSS2 receptors, both overexpressed in smokers and former smokers. Tobacco-smoke airway exposure is also characterized by a chronic inflammation with activation of inflammatory cells and cytokine release including interleukin-6 (IL-6). A high release of cytokine in response to viral infection is documented in COVID-19 patients with adverse clinical outcomes and IL-6 is a key element of the cytokine storm syndrome leading to multi-organ damage. CONCLUSIONS: Patients with cancers of the upper and lower airways might be at increased risk of infection, morbidity and mortality from COVID-19 also because of tobacco exposure, a key factor in triggering inflammation, immunity and cancer.

Weekly hypofractionated radiation therapy in elderly non-resectable cutaneous squamous cell carcinoma of the head and neck region.

INTRODUCTION: Treatment of inoperable cutaneous squamous cell carcinoma (cSCC) of the head and neck region is still debated. CASE REPORT: We report an original case of cure of cSCC of the head and neck region with weekly hypofractionated radiation therapy with megavoltage electrons prescribed for locally advanced inoperable disease. RESULTS: Weekly hypofractionated radiotherapy assured complete regression and was well-tolerated. CONCLUSION: The real efficacy of this treatment in the therapeutic arsenal remains to be defined. A clinical trial is ongoing to test the use of 8 weekly fractions of 8 Gy hypofractionated RT regimens in non-resectable cSCC cases.

Research Goal-Driven Data Model and Harmonization for De-Identifying Patient Data in Radiomics.

There are various efforts in de-identifying patient's radiation oncology data for their uses in the advancement of research in medicine. Though the task of de-identification needs to be defined in the context of research goals and objectives, existing systems lack the flexibility of modeling data and normalization of names of attributes for accomplishing them. In this work, we describe a de-identification process of radiation and clinical oncology data, which is guided by a data model and a schema of dynamically capturing domain ontology and normalization of terminologies, defined in tune with the research goals in this area. The radiological images are obtained in DICOM format. It consists of diagnostic, radiation therapy (RT) treatment planning, RT verification, and RT response images. During the DICOM de-identification, a few crucial pieces of information are taken about the dataset. The proposed model is generic in organizing information modeling in sync with the de-identification of a patient's clinical information. The treatment and clinical data are provided in the comma-separated values (CSV) format, which follows a predefined data structure. The de-identified data is harmonized throughout the entire process. We have presented four specific case studies on four different types of cancers, namely glioblastoma multiforme, head-neck, breast, and lung. We also present experimental validation on a few patients' data in these four areas. A few aspects are taken care of during de-identification, such as preservation of longitudinal date changes (LDC), incremental de-identification, referential data integrity between the clinical and image data, de-identified data harmonization, and transformation of the data to an underlined database schema.

[The 8th edition of the TNM staging system-a curse or a blessing for oropharyngeal carcinoma?] / Die 8. Version der TNM-Klassifikation ­ Fluch oder Segen für das Oropharynxkarzinom?

At the beginning of 2017, the 8th edition of the TNM classification was presented. For oropharyngeal carcinoma, this was accompanied by a paradigm shift, as a separation of the classification depending on the association with human papillomavirus (HPV) status has been established. By considering the literature, this paper provides an overview of the characteristics of HPV-associated carcinomas, the new features of the TNM classification, and the existing points of discussion. The revision has improved the prognostic significance of the TNM classification; however, there are still tumor- and patient-dependent influencing factors that must be considered for future versions.

Radiation Therapy and Mandibular Osteoradionecrosis: State of the Art.

PURPOSE OF REVIEW: This article aims to provide an update on literature data related to mandibular osteoradionecrosis (MORN) secondary to the irradiation of the head and neck region. RECENT FINDINGS: Radiotherapy (RT) plays a crucial role in the contemporary management of head and neck cancer (HNC) patients and, despite intensity-modulated technique (IMRT), mandibular osteoradionecrosis (MORN) remains a significant RT-related complication. Based on its clinical manifestation, MORN can negatively affect patients' quality of life. Preventive interventions should be prioritized. This manuscript is expected to represent an opportunity to guide a clear proposal for clinical measures in the individual MORN situations.

An Update on Surgical Margins in the Head Neck Squamous Cell Carcinoma: Assessment, Clinical Outcome, and Future Directions.

PURPOSE OF REVIEW: Failure to achieve tumor-free margins is the single largest cause of death for head neck cancer patients. At the same time, it is the only factor that is in complete control of the surgeon. This review summarizes evidence for the definition, clinical implications, and methods to achieve optimal margins. RECENT FINDINGS: The previous universally followed definition of adequate margin (5 mm in final histopathology) has been disputed. Various biological, optical, and imaging adjuncts can aid in achieving optimal margins. Extent of resection and margins in human papilloma virus (HPV)-positive oropharyngeal cancers and following induction chemotherapy remain controversial. Though practiced widely, frozen section-guided margin revision has not conclusively shown improved local control rates. The role of molecular assessment of margins is promising but not established. The definition of adequate margin differs according to the site in the head neck region. Currently, the 5-mm margin at final histopathology is the most commonly accepted definition of an "adequate" margin.

Retrospective evaluation of the safety of low-level laser therapy/photobiomodulation in patients with head/neck cancer.

BACKGROUND: The standard therapeutic approach for locally advanced head and neck cancer is optimal use of radiation therapy with or without concomitant chemotherapy. The most common and distressing acute complication of such therapies is oral/pharyngeal mucositis that may be associated with severe morbidity and can interfere with the planned administration of therapy. METHODS: We have identified all patients diagnosed with head/neck cancer between 2005 and 2009, having received radiotherapy with or without cisplatin-based chemotherapy. Radiotherapy consisted of intensity-modulated radiation therapy (IMRT) in all patients. In patients with grade > 2 mucositis, photobiomodulation (PBM) consisted of three sessions of low-level laser irradiation weekly, in accordance with recently published recommendations for PBM. Patients who did not receive PBM were those for whom that approach was not requested by the radiotherapists and those who declined it. RESULTS: Two hundred twenty-two patients (62%) received PBM and 139 did not (39%). The patient's characteristics were equally distributed between the two groups. For overall survival, time to local recurrence, and progression-free survival, there was no statistical evidence for a difference in prognosis between patients with and without PBM. In a multivariate analysis, after adjusting for known prognostic factors, we found no statistical evidence that PBM was related to overall survival, progression-free survival, or local recurrence. CONCLUSIONS: Our results show evidence of no effect of PBM upon overall survival, time to local recurrences, and disease-free survival of patients with head and neck cancer treated with radiotherapy with/without chemotherapy.