A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

BACKGROUND: Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. METHODS: Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. RESULTS: Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). CONCLUSIONS: Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018;124:2948-55. © 2018 American Cancer Society.

Image-guidance triggered adaptive radiation therapy in head and neck squamous cell carcinoma: single-institution experience and implications for clinical practice.

PURPOSE: To report frequency and timing of adaptive radiotherapy (ART) and assess patient, disease, and treatment-related characteristics potentially triggering the need for such adaptive replanning in head and neck squamous cell carcinoma (HNSCC). METHODS: Medical records of HNSCC patients treated with definitive intensity modulated radiation therapy (IMRT) with or without concurrent systemic chemotherapy were reviewed retrospectively to identify patients undergoing image-guidance triggered adaptive replanning. Clinico-demographic characteristics of patients undergoing ART were compared with patients treated without adaptation using the chi-square test. RESULTS: Two hundred patients with squamous cell cancers of the oropharynx, larynx, or hypopharynx treated with definitive IMRT between 2014 to 2019 comprised the study cohort. Twenty-seven (13.5%) patients underwent adaptive replanning during treatment at a median of 17 fractions (inter-quartile range 14-24 fractions). There were no significant differences in the baseline patient (age, gender), disease (site of primary, staging/grouping), and treatment-related characteristics (dose-fractionation, chemotherapy usage) in patients undergoing ART compared to those treated without adaptation. Weight loss during IMRT emerged as a significant factor predicting the need for ART; patients having ≥10% weight loss from baseline were more likely to undergo treatment adaptation compared to patients with <10% weight loss (p = 0.0002). There was variable impact of ART on dose-volume statistics of organs-at-risk such parotid glands and spinal cord. CONCLUSION: Image-guidance triggered ART for HNSCC is not associated with significant improvement in OAR dosimetry. However, weight loss during definitive IMRT can be a potentially useful trigger for identifying patients who are most likely to benefit from such adaptive replanning.

Predicting IDH subtype of grade 4 astrocytoma and glioblastoma from tumor radiomic patterns extracted from multiparametric magnetic resonance images using a machine learning approach.

Background and purpose: Semantic imaging features have been used for molecular subclassification of high-grade gliomas. Radiomics-based prediction of molecular subgroups has the potential to strategize and individualize therapy. Using MRI texture features, we propose to distinguish between IDH wild type and IDH mutant type high grade gliomas. Methods: Between 2013 and 2020, 100 patients were retrospectively analyzed for the radiomics study. Immunohistochemistry of the pathological specimen was used to initially identify patients for the IDH mutant/wild phenotype and was then confirmed by Sanger's sequencing. Image texture analysis was performed on contrast-enhanced T1 (T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on MR image slices followed by single-slice multiple sampling image augmentation. Both whole tumor multislice segmentation and single-slice multiple sampling approaches were used to arrive at the best model. Radiomic features were extracted, which included first-order features, second-order (GLCM-Grey level co-occurrence matrix), and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression, followed by radiomic classification using Support Vector Machine (SVM) and a 10-fold cross-validation strategy for model development. The area under the Receiver Operator Characteristic (ROC) curve and predictive accuracy were used as diagnostic metrics to evaluate the model to classify IDH mutant and wild-type subgroups. Results: Multislice analysis resulted in a better model compared to the single-slice multiple-sampling approach. A total of 164 MR-based texture features were extracted, out of which LASSO regression identified 14 distinctive GLCM features for the endpoint, which were used for further model development. The best model was achieved by using combined T1C and T2W MR images using a Quadratic Support Vector Machine Classifier and a 10-fold internal cross-validation approach, which demonstrated a predictive accuracy of 89% with an AUC of 0.89 for each IDH mutant and IDH wild subgroup. Conclusion: A machine learning classifier of radiomic features extracted from multiparametric MRI images (T1C and T2w) provides important diagnostic information for the non-invasive prediction of the IDH mutant or wild-type phenotype of high-grade gliomas and may have potential use in either escalating or de-escalating adjuvant therapy for gliomas or for using targeted agents in the future.

Objective assessment of swallowing function after definitive concurrent (chemo)radiotherapy in patients with head and neck cancer.

The aim of this study was to objectively assess swallowing function and factors impacting it after curative intent definitive (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Swallowing function was studied in a cohort of 47 patients with locoregionally advanced (T1-4, N0-3) HNSCC treated with definitive CRT. Objective assessment of swallowing function was done using modified barium swallow (MBS) at baseline (pre-CRT) and subsequent follow-ups. Scoring of MBS was done using penetration-aspiration scale (PAS). Abnormal swallowing was defined in terms of incidence and severity of penetration-aspiration, pharyngeal residue, postural change, and regurgitation. Aspiration, residual, postural change, and regurgitation were present on baseline pre-CRT assessment in 9 (19%), 11 (23%), 10 (21%), and 5 (10%) patients that increased to 11 (29%), 11 (29%), 12 (32%), and 10 (26%) patients, respectively, at 6-month post-CRT evaluation. The proportion of patients with high PAS scores (3-7) increased from 27% at baseline to 37% at 6-month post-CRT evaluation. Among patients (n = 34) with low PAS scores (≤2) at baseline, additional impairment of swallowing function was seen in 53 and 46% at 2- and 6-month assessment, respectively. Residue (44%) and aspiration (18%) domains were impaired in a higher proportion of patients after CRT. Thin and thick barium had higher aspiration and residue function impairment, respectively. Patients with pre-CRT poor subjective swallowing function (P = 0.004), hypopharyngeal primary (P = 0.05), and large tumor volume (P = 0.05) had significantly worse objective swallowing function at baseline as demonstrated by pretreatment PAS scores. This study provides useful information regarding patterns of objective swallowing dysfunction in patients treated with definitive (chemo)radiotherapy. There is significant impairment of objective swallowing function in all domains following CRT, with residue and aspiration domains being affected most significantly.

Outcomes of Palliative Radiotherapy in Metastatic Epidural Spinal Cord Compression in Lung Cancer-A Prospective Observational Study from Tata Memorial Hospital.

Background Metastatic epidural spinal cord compression (MESCC) secondary to lung cancer (LC) is a debilitating complication associated with poor prognosis and is commonly treated with radiotherapy (RT). There is no consensus for RT dose fractionation in spinal cord compression. Methods Forty consecutive patients of LC with radiological evidence of MESCC treated with palliative RT were evaluated for functional outcomes (pain, ambulation, and sphincter function) at 2-, 4-, and 24-week post RT completion. Pain assessment was done using visual analogue scale (VAS) and response was categorized according to international consensus criteria, ambulation status (AS) using Tomita's scale, and sphincter function by the presence or absence of a catheter. Overall survival (OS) was assessed using Kaplan-Meier method and compared using log-rank test. Impact of potential prognostic factors on survival was also analyzed and p -value ≤0.05 was considered significant. Results Sixteen, 22, and two patients received 8 Gy single fraction (SF), 20 Gy in five fractions (20/5), and 30 Gy in 10 fractions (30/10), respectively. At 2 weeks, overall response (OR) rates of pain, ambulation, and sphincter control were 73, 81, and 81%, respectively. At 4 and 24 weeks, 93.7, 84.3, 87.5% and 88, 94, 76.5% had OR, respectively. Median OS was 4 months. Six- and 12-months OS was 50 and 37.5%. Nonsignificant difference in OS was seen between SF and 20/5 fractions (median 2.2 vs. 7.1 months, p = 0.39). Age ≤50 years was the only significant factor ( p <0.05) in univariate analysis for OS. Conclusion Radiotherapy provided equivalent pain control, ambulation, and sphincter function compared with reported literature in MESCC. Nonsignificant difference in OS exists between SF and multifraction RT regimens.

Sociodemographic, clinical profile, and psychiatric morbidities among patients with attempted suicide in a tertiary care center: A study from Central India.

BACKGROUND: Suicide is a major public health concern and is considered one of the leading causes of death globally. Previous suicidal attempts can be considered as a predictor of underlying psychiatric illness. Identifying factors behind suicidal attempt can help mental health professionals for early diagnosis and treatment as well as designing effective suicide prevention strategies. AIM: The aim of the study is to assess sociodemographic, clinical characteristics, and prevalence of psychiatric morbidities among patients with attempted suicide. METHODS: A cross-sectional study was conducted in the emergency department of tertiary care hospital; patients of attempted suicide attending emergency from January 1, 2014, to January 1, 2020, constituted the sample for the study. Data were collected using semi-structured questionnaire which contained sociodemographic and clinical variables. All the subjects were administered mini-international neuropsychiatric interview (MINI), MINI Kid was applied for subjects <18 years, and MINI Plus was applied for subjects above 18 years. Patients were diagnosed according to the ICD-10 Classification of Mental and Behavioral Disorders for research. RESULTS: Suicide attempt was seen more commonly in males, and the most common age group is between 21 and 40 years residing in urban settings. The most common method was consumption of unknown substances (75.35%). Factors leading to suicide are multidimensional in nature. 30.4% of the patients had impulsive traits. 86.5% of people who attempted suicide had a history of psychiatric illness. Detailed assessment of patients for psychiatric illness and psychosocial factors is crucial for planning suicide prevention strategies and policymaking. CONCLUSIONS: Young population is at high risk for suicide. More than 80% of these have diagnosable psychiatric illness.

Optimal Standardized Uptake Value Threshold for Auto contouring of Gross Tumor Volume using Positron Emission Tomography/Computed Tomography in Patients with Operable Nonsmall-Cell Lung Cancer: Comparison with Pathological Tumor Size.

PURPOSE: Incorporating 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) for gross tumor volume (GTV) delineation is challenging due to varying tumor edge based on the set threshold of the standardized uptake value (SUV). This study aims to determine an optimal SUV threshold that correlates best with the pathological tumor size. MATERIALS AND METHODS: From January 2013 to July 2014, 25 consecutive patients of operable nonsmall-cell lung cancer (NSCLC) who underwent staging18F-FDG-PET/CT before surgical resection were included in the test cohort and 12 patients in the validation cohort. GTVs were delineated on the staging PET/CT by automatic delineation using various percentage threshold of maximum SUV (SUVmax) and absolute SUV. The maximum pathological tumor diameter was then matched with the maximum auto-delineated tumor diameter with varying SUV thresholds. First-order linear regression and Bland-Altman plots were used to obtain an optimal SUV threshold for each patient. Three radiation oncologists with varying degrees of experiences also delineated GTVs with the visual aid of PET/CT to assess interobserver variation in delineation. RESULTS: In the test set, the mean optimal percentage threshold for GTV was SUVmax of 35.6%±18.6% and absolute SUV of 4.35 ± 1.7. In the validation set, the mean optimal percentage threshold SUV and absolute SUV were 36.9 ± 16.9 and 4.1 ± 1.6, respectively. After a combined analysis of all 37 patients, the mean optimal threshold was 36% ± 17.9% and 4.27 ± 1.7, respectively. Using Bland-Altman plots, auto-contouring with 40% SUVmax and SUV 4 was in greater agreement with the pathological tumor diameter. CONCLUSION: Automatic GTV delineation on PETCT in NSCLC with percentage threshold SUV of 40% and absolute SUV of 4 correlated best with pathological tumor size. Auto-contouring using these thresholds will increase the precision of radiotherapy contouring of GTV and will save time.

Protocol for a phase II randomised controlled trial of TKI alone versus TKI and local consolidative radiation therapy in patients with oncogene driver-mutated oligometastatic non-small cell lung cancer.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have significantly improved the progression-free survival (PFS) of metastatic non-small cell lung cancer (NSCLC) with oncogene mutations of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) compared with systemic therapy alone. However, the majority eventually develop resistance with a median PFS of 8-12 months. The pattern of failure studies showed disease relapse at the original sites of the disease-harbouring resistant tumour cells. METHODS AND ANALYSIS: This study is designed as a phase II randomised controlled trial to evaluate the efficacy of local consolidative radiation therapy (LCRT) in addition to TKI in upfront oligometastatic NSCLC. Patients will be screened at presentation for oligometastases (≤5 sites) and will start on TKI after confirmation of EGFR or ALK mutation status. After initial TKI for 2-4 months, eligible patients will be randomised in a 1:1 ratio with stratification of oligometastatic sites (1-3 vs 4-5), performance status of 0-1 versus 2 and brain metastases. The standard arm will continue to receive TKI, and the intervention arm will receive TKI plus LCRT. Stereotactic body radiation therapy will be delivered to all the oligometastatic sites.The primary end point is PFS, and secondary end points are overall survival, local control of oligometastatic sites, toxicity and patient-reported outcomes. The sample size calculation took a median PFS of 10 months in the standard arm. To detect an absolute improvement of 7 months in the interventional arm, with a one-sided alpha of 5% and 80% power, a total of 106 patients will be accrued over a period of 48 months. ETHICS AND DISSEMINATION: The study is approved by the Institutional Ethics Committee II of Tata Memorial Centre, Mumbai, and registered with Clinical Trials Registry-India, CTRI/2019/11/021872, dated 5 November 2019. All eligible participants will be provided with a participant information sheet and will be required to provide written informed consent for participation in the study. The study results will be presented at a national/international conference and will be published in a peer-reviewed journal.

Depth of invasion in early oral cancers- is it an independent prognostic factor?

INTRODUCTION: Depth of invasion (DOI) has been incorporated into oral cancer staging. Increasing DOI is known to be associated with an increased propensity to neck metastasis and adverse tumor factors and hence may not be an independent prognosticator but a surrogate for a biologically aggressive tumor. METHODS: 570 patients, median follow up 79.01 months from a previously reported randomized trial (NCT00193765) designed to establish appropriate neck treatment [elective neck dissection (END) vs therapeutic neck dissection (TND)] in clinically node-negative early oral cancers were restaged (nT) according to AJCC TNM 8th edition. Overall survival (OS) was estimated for the entire cohort, END, and TND arms. Multivariate analysis performed for stratification and prognostic factors, and interaction term between revised T-stage and neck treatment, for tumours with DOI≤10mm. Presence of adverse factors was compared between nT3 (DOI>10 mm) and those with DOI≤10 mm. RESULTS: Stage migration occurred in 44.38% of patients. 5-Year OS was nT1-79%, nT2-69.4% and nT3-53.8%, (p < 0.001). In TND arm 5-year OS was nT1-81.1% versus nT2-65%,p = 0.004, while that in END arm was nT1 -76.9% versus nT2 -73.7%,p = 0.73. There was a significant interaction between T stage and neck treatment (p = 0.03). T3 tumors (>10 mm) were associated with a higher proportion of adverse factors (occult nodal metastasis, p = 0.035; LVE/PNI, p = 0.001). CONCLUSION: Elective neck treatment negates the prognostic impact of DOI for early oral cancers (T1/T2 DOI≤10 mm). T3 tumors with DOI>10 mm have a higher association with other adverse risk factors resulting in poorer outcomes in spite of elective neck dissection.

Prognostic factors and outcome analysis of submandibular gland cancer: a clinical audit.

PURPOSE: To retrospectively review a long-term, single-institution experience of subjects with submandibular gland malignancies treated with definitive locoregional therapy with an aim to identify clinicopathologic variables that correlate with outcomes. MATERIALS AND METHODS: A comprehensive chart review of 47 patients presenting to the institute from 1993 to 2005 with a histologic diagnosis of submandibular salivary gland cancer was performed to extract demographic data, clinicopathological characteristics, and treatment details. Clinical and pathologic factors were correlated with locoregional control, distant metastases free survival, and disease-free survival using log-rank test and Cox proportional hazards model for univariate and multivariate analysis, respectively. RESULTS: With a median follow-up of 29 months (interquartile range, 13 to 64 months), the actuarial 5-year locoregional control, distant metastasis-free survival, and disease-free survivals of the entire cohort were 80.5%, 86.1%, and 71.8%, respectively. Overall stage grouping (P = .008), perineural invasion (P = .04), and radiotherapy dose (P = .033) were significant predictors of locoregional control. Overall stage grouping (P = .014) and T stage (P = .05) also affected disease-free survival. Extraglandular involvement showed a trend toward poorer outcome. CONCLUSIONS: Submandibular gland cancer is a rare disease with histologic diversity and variable clinical behavior. Overall stage grouping and perineural invasion remain the most significant predictors of outcome. Adequate doses of adjuvant radiotherapy improve locoregional control in high-risk patients.

Salvage surgery in head and neck cancer: Does it improve outcomes?

BACKGROUND: Studies reporting outcomes of salvage surgery in locally advanced head and neck squamous cell carcinoma (LAHNSCC) have inherent biases like biological and temporal selection. Our study considered all patients deemed fit for salvage surgery and compared to those who underwent surgery versus those who refused it thus throwing light on the real world benefit of salvage surgery. METHODS: This was a post hoc analysis of a phase 3 randomized trial conducted between 2012 and 2018. Out of 536 LAHNSCC patients randomised in the study, 113 patients had residual disease or recurrent disease and were planned for salvage surgery in a multidisciplinary clinic. Patients were divided into 2 cohorts for comparison, willing for salvage surgery (n = 91) and unwilling for salvage surgery(n = 22). The primary endpoint was overall survival. RESULTS: The median follow up was 28.7 months (95%CI 23.9-33.5 months). Out of the 91 patients who were willing for salvage surgery, 78 underwent same. The median survival in cohort of patients willing for salvage surgery was 22.0 months (95%CI 10.1-33.9) while it was 9.7 months (95%CI 6.6-12.8) in patients who were unwilling for salvage surgery (HR = 0.262 95%CI HR 0.147-0.469, p = 0.000). CONCLUSION: Salvage surgery leads to a substantial improvement in outcomes in head and neck cancers and should be the de facto standard of care in patients who are eligible for the same.

Role of thoracic consolidation radiation in extensive stage small cell lung cancer: A systematic review and meta-analysis of randomised controlled trials.

Extensive stage small cell lung cancer (ES-SCLC) carries a poor prognosis, and the thoracic progression is common. Consolidation radiation to thoracic disease (cRT) could improve progression-free survival (PFS) and overall survival (OS). We conducted an electronic search of PubMed and Embase with no language, year or publication status restrictions and evaluated randomised controlled trials (RCTs) addressing the role of cRT in ES-SCLC. Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines for systematic review and Cochrane methodology for meta-analysis were followed. Effect estimates (hazard ratios [HRs] and confidence intervals [CIs]) and risk ratios were extracted, with a fixed/random-effects model created to estimate treatment effects. I2 statistics and heterogeneity statistics were performed. Comprehensive and systematic search identified 1107 records, after removal of duplicate records screened 922 records, assessed 31 full-text articles for eligibility and 3 RCTs with a total of 690 patients were included. Pooled analysis showed cRT significant improved PFS (p < 0.0001) with HR 0.72 (95% CI: 0.61-0.83, I2-0%). In addition, cRT significantly (p < 0.001) reduced the risk of thoracic progression as the first site of progression with a relative risk of 0.52 (95% CI: 0.44-0.61, I2-0%). OS analysis showed no significant (p = 0.36) benefit with HR of 0.88 (95% CI 0.66-1.18, I2-52%) with cRT. Pooled meta-analysis of 3 randomised controlled studies shows consolidation thoracic radiotherapy (RT) offers significant improvement in PFS and reduction in thoracic failures. Further research on subclassification of ES-SCLC (limited vs extensive metastasis), optimise strategy for RT integration (sequential vs concurrent) and optimal RT dose is needed to identify the subset of ES-SCLC likely to have significant OS benefit.

Influence of comorbidity on therapeutic decision making and impact on outcomes in patients with head and neck squamous cell cancers: Results from a prospective cohort study.

BACKGROUND: High prevalence of comorbidity in head and neck squamous cell carcinoma (HNSCC) often lead to suboptimal treatment. The presence study aims to evaluate the presence of comorbidity, its impact on therapeutic decision making, treatment compliance, and overall survival in HNSCC. METHODS: Five hundred eighteen patients with nonmetastatic HNSCC, elder than 18 years of age, without any prior history of cancer or anticancer treatment in the last 5 years were evaluated using Adult Comorbidity Evaluation 27 (ACE 27) index. RESULTS: Two hundred ninety three (56.6%) patients had comorbidity, and 20.6% had deviation from the ideal treatment plan. Higher grade of comorbidity led to less likely completion of guideline-concordant therapy (moderate ACE 27 vs none: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26-0.82, P < .01*; severe ACE 27 vs none: OR 0.23, 95% CI 0.08-0.57, P < .01*). Patients who completed guideline-concordant treatment had the best outcomes as compared to those who could not (median survival: not reached vs 9.56 months, hazard ratio 3.66, 95% CI: 2.8-4.79; P < .01*). CONCLUSION: Presence of increasing severity of comorbidity in HNSCC influences therapeutic decision making. Survival outcomes are poorer in patients receiving guideline-discordant treatment.

Optimal timing of fluorine-18-fluoromisonidazole positron emission tomography/computed tomography for assessment of tumor hypoxia in patients with head and neck squamous cell carcinoma.

OBJECTIVES: The aim of this study was to identify the optimal timing of fluorine-18-fluoromisonidazole (F-MISO) PET/CT imaging to assess hypoxia in patients with head and neck squamous cell carcinoma. PATIENTS AND METHODS: Eighteen patients underwent pretreatment F-MISO PET/CT imaging after providing written informed consent. PET scans were acquired at 1, 3, and 5 h after injection of the radionuclide. The mean standardized uptake value (SUV) within a spherical region of interest placed on the contralateral neck musculature at the level of the largest tumor dimension was labeled as background. A value 1.5 times the background was deemed the threshold for significant hypoxia. Using this threshold, volumetric regions of interest encompassing the tumor were placed and hypoxic tumor volume (HTV) was generated for the primary tumor. Repeated-measures analysis of variance was used to compare the F-MISO PET/CT metrics across the three time-points. The volume of the primary tumor was also correlated with HTV. RESULTS: The mean SUV of the background decreased consistently over time, resulting in increased focality of F-MISO uptake in the tumor tissues. Analysis of variance showed statistically significant differences in the mean SUV measurements of the background between the 1-h and the 3-h time-points (P=0.034) as well as the 1-h and the 5-h time-points (P=0.034). In parallel, the mean HTV increased from 1.72 cm at 1 h after injection to 6.52 cm at 3 h and further to 7.24 cm at 5 h, with a statistically significant difference between the 1-h and the 3-h scans (P=0.023) and the 1-h and the 5-h scans (P=0.023). There was a moderately good positive correlation between gross tumor volume on planning computed tompography (CT) and HTV at 3 h on the F-MISO scan (Pearson's correlation co-efficient 'r'=+0.753; P<0.0001). CONCLUSION: The contrast resolution of F-MISO PET/CT scans in head and neck squamous cell carcinoma is suboptimal with early image acquisition, but improves significantly after delayed imaging. Increasing volume of tumor at the primary site is associated with an increase in hypoxia.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

Survey of return to work of head and neck cancer survivors: A report from a tertiary cancer center in India.

BACKGROUND: The rates and factors associated with the return to work of head and neck cancer survivors from low- and middle-income countries, such as India, are largely unknown. METHODS: We conducted a preliminary cross-sectional survey of 250 consecutive eligible head and neck cancer survivors (age <60; ≥6 months posttreatment) to identify return to work rates and sociodemographic, clinical, and quality of life (QOL; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions [EORTC-QLQ-C30] and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Head and Neck 35-questions [EORTC-QLQ-H&N35]) correlates. RESULTS: In our cohort, 92.4% of the patients were employed pretreatment, 65.6% and 81.2% returned to work at 6 months posttreatment and by the time of the survey (median follow-up 19 months), respectively. Family structure (<2 male children, p = .008; eldest child age <20 years, p = .04), a higher level of education (vocational or professional training, p = .013) and female sex (p = .001) were associated with higher return to work. Head and neck cancer survivors who returned to work had better global quality of life (QOL; p = .014) and less coughing (p = .001) but more problems related to sticky saliva (p = .004). CONCLUSION: Further studies are needed to address the large unmet needs regarding identification and amelioration of barriers to return to work for head and neck cancer survivors in low- and middle-income countries, such as India. © 2017 Wiley Periodicals, Inc. Head Neck 39: 893-899, 2017.

Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations.

Human papillomavirus (HPV) associated head and neck squamous cell cancers (HNSCC) have become increasingly common in the West, but the same cannot be said about India. These cancers have a different biology and confer a better prognosis, however, its current role in the management of patients in India is not clearly defined. At the 35th Indian Cooperative Oncology Network conference held in September 2016, a panel of radiation, surgical and medical oncologists, pathologists, and basic scientists from across the country having experience in clinical research with respect to HPV in HNSCC reviewed the available literature from India. All the ideas and facts were thereafter collated in this report. Various topics of controversy in dealing with the diagnosis and management of HPV-associated HNSCC have been highlighted in this report in context to the Indian scenario. Furthermore, the prevalence of the same and its association with tobacco and high-risk sexual behavior has been touched on. Conclusively, a set of recommendations has been proposed by the panel to guide the practicing oncologists of the country while dealing with HPV-associated HNSCC.