N0 neck trial: Does intensification of follow-up (Ultrasound + Physical Examination) influence outcomes in early-stage oral cancer?

AIM OF THE STUDY: We previously reported a survival benefit of elective neck dissection (END) over therapeutic neck dissection (TND) in patients with clinically node-negative early-stage oral cancer. We now report the results of the second question in the same study addressing the impact of adding neck ultrasound to physical examination during follow-up on outcomes. METHODS: Patients with lateralized T1/T2 oral squamous cell carcinoma (SCC) were randomized to END or TND and to follow-up with physical-examination plus neck ultrasound (PE+US) versus physical-examination (PE). The primary endpoint was overall survival (OS). RESULTS: Between January 2004 and June 2014, 596 patients were enrolled. This is an intention to treat analysis of 592 analysable patients, of whom 295 were allocated to PE+US and 297 to PE with a median follow-up of 77.47 months (interquartile range (IQR) 54.51-126.48). There was no significant difference (unadjusted hazard ratio [HR], 0.92, 95% CI, 0.71-1.20, p = 0.54) in 5-year OS between PE+US (70.8%, 95% CI, 65.51-76.09) and PE (67.3%, 95% CI, 61.81-72.79). Among 131 patients with neck node relapse as the first event, the median time to relapse detection was 4.85 (IQR 2.33-9.60) and 7.62 (IQR 3.22-9.86) months in PE+US and PE arms, respectively. The N stage in the PE+US arm was N1 33.8%, N2a 7.4%, N2b/c 44.1% and N3 14.7% while in PE was N1 28.6%, N2a 9.5%, N2b/c 39.7%, N3 20.6% and unknown 1.6%. CONCLUSION: Adding neck ultrasound to physical examination during follow-up detects nodal relapses earlier but does not improve overall survival.

Surgical tumour resection deregulates Hallmarks of Cancer in resected tissue and the surrounding microenvironment.

Surgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissue from breast (BRC) (n=81) and head/neck squamous cancer (HNSC) patients (n=10) at the beginning (A), during (B) and end of surgery (C). Tumor/normal RNA from 46/81 breast cancer patients was subjected to mRNA-Seq using Illumina short-read technology, and from nine HNSC patients to whole transcriptome microarray with Illumina BeadArray. Pathways and genes involved in 7 of 10 known cancer hallmarks, namely, tumour promoting inflammation (TNF-A, NFK-B, IL-18 pathways), activation of invasion & migration [(various Extracellular Matrix (ECM) related pathways, cell migration)], sustained proliferative signaling (K-Ras Signaling), evasion of growth suppressors (P53 signaling, regulation of cell death), deregulating cellular energetics (response to lipid, secreted factors, adipogenesis), inducing angiogenesis (hypoxia signaling, myogenesis), and avoiding immune destruction (CTLA4 and PDL1) were significantly deregulated during surgical resection (time-points A vs B vs C). These findings were validated using NanoString assays in independent pre/intra/post-operative breast cancer samples from 48 patients. In a comparison of gene expression data from biopsy (analogous to time-point A) with surgical resection samples (analogous to time-point C) from The Cancer Genome Atlas (TCGA) study, the top deregulated genes were the same as identified in our analysis, in five of the seven studied cancer types. This study suggests that surgical extirpation deregulates the hallmarks of cancer in primary tumors and adjacent normal tissue across different cancers. Implications: Surgery deregulates hallmarks of cancer in human tissue.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial.

PURPOSE: The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). METHODS AND MATERIALS: This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. RESULTS: Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). CONCLUSIONS: The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Clinical studies with Cannabis in India - A need for guidelines for the investigators and ethics committees.

Cannabis is one of the world's oldest cultivated plants and the most commonly used recreational drug worldwide. The plant relevant for medicinal use is Cannabis sativa that has two pharmacologically active ingredients - delta-9-tetrahydrocannabinol that is psychoactive and cannabidiol that does not have psychotropic activity. The policy tapestry of Cannabis has undergone a significant change in the past few decades worldwide. Different countries have diverse policies, ranging from classifying use of Cannabis as illicit, to legalization of its use, both for medicinal and recreational purposes. Cannabis products are approved for use, for instance, in multiple sclerosis and Dravet syndrome (US Food Drug and Administration). Against this backdrop, we find that the knowledge foundations for use of Cannabis in clinical trials in India are still evolving. Conducting ethical research within a clinical trials framework is essential to understand dosing, formulation, shelf life, drug-drug interaction, tolerability, and safety before establishing its utility for various indications. In the absence of guidelines or a regulatory framework for conduct of these studies, the various Institutional Ethics Committees (IECs), which are responsible for reviewing projects related to Cannabis, face unique challenges with respect to the basic requirements. The principal investigators (PIs) are equally strained to find local guidance, recommendations, and literature in support of their application to the respective IEC, thus leading to an impasse and delay in initiating the proposed clinical studies with Cannabis. The present article addresses considerations, questions, and issues that affect the conduct of these clinical studies and recommends mandatory documents and some suggested guidelines for use by both PIs and IECs to take studies with Cannabis forward until such time that an interdisciplinary regulatory framework is firmed up by regulatory authority.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Oral cavity adjuvant therapy (OCAT) -a phase III, randomized controlled trial of surgery followed by conventional RT (5 fr/wk) versus concurrent CT-RT versus accelerated RT (6fr/wk) in locally advanced, resectable, squamous cell carcinoma of oral cavity.

BACKGROUND: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology. PATIENTS AND METHODS: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC). RESULTS: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60). CONCLUSIONS: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification. CLINICAL TRIAL REGISTRATION: NCT00193843.

CT-Based Screening for Pulmonary Metastases in Head and Neck Squamous Cell Cancers: Diagnostic Accuracy and Cost Comparison with PET-CECT.

This study's objective was to compare detection rates of radiograph, computed tomography (CT), and positron emission tomography-contrast-enhanced computed tomography (PET-CECT) for pulmonary metastasis/synchronous primary lung tumors in head and neck squamous cell cancer (HNSCC) and its association with clinico-radio-pathological factors. Our retrospective study included 837 HNSCC patients from January 2012 to December 2017. Lung nodules were characterized on CT as benign, indeterminate, and metastatic. The true detection rate and statistical significance of associated risk factors were calculated. Risk factors for metastasis were determined using univariate and multivariate logistic regression models. Seventy-five (8.9%) patients had pulmonary metastasis and 3 (0.3%) had second lung primary. Detection rate of pulmonary metastasis by CT was higher (sensitivity-97.3%, specificity-97.2%) as compared to radiograph (sensitivity 49% and specificity 89%). Correlation was found between pulmonary and extra-pulmonary metastasis and N classification (P = 0.01, P = 0.02) and positive low jugular node (P = 0.001, P = 0.001). Using PET-CECT in place of CT costed an extra outlay of 7,033,805 INR (95,551.85 USD) while detecting distant metastasis in only 4 (0.47%) extra cases. Chest CT is a useful pulmonary metastases screening tool in advanced HNSCC patients with reasonable imaging cost as compared to PET-CT.

MR imaging-based risk stratification scoring system to predict clinical outcomes in carotid body tumors.

Objectives: This study aims to evaluate the role of pretherapy MRI in predicting outcomes in carotid body tumors and propose a grading system for high- and low-risk characteristics. Materials and methods: A retrospective observational study of 44 patients with 51 lesions was carried out from year 2005 to 2020. MR images were reviewed for characteristics of carotid body tumor, and a score was given that was correlated with intra- and postoperative findings. The various other classifications and our proposed Mahajan classification were compared with Shamblin's classification. The area under the curve and ROC curves were used to present the accuracy of different predictive models. Results: Our scoring system allotted a score of 0 to 15 on the basis of MRI characteristics, with scores calculated for patients in our study ranging from 0 to 13. Lesions with scores of 0-6 were considered low risk (45%), and scores of 7-15 were regarded as high risk for surgery (55%). The Mahajan classification stages tumors into four grades: I (10%), II (20%), IIIa (8%), and IIIb (62%). The frequency of vascular injury was 50% in category I and 64% in category IIIb. The frequency of cranial nerve injury was 50%, 66%, and 27% in categories I, II, and IIIb. Conclusion: The Mahajan classification of CBTs evaluates high-risk factors like the distance of the tumor from the skull base and the angle of contact with ICA, which form the major predictors of neurovascular damage and morbidity associated with its surgery. Though the Shamblin classification of CBT is the most widely accepted classification, our proposed Mahajan classification system provides an imaging-based alternative to prognosticate surgical candidates preoperatively.

Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study.

BACKGROUND: Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness. METHODS: A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC. RESULTS: Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores. CONCLUSIONS: Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting.

Prognostic Value of Radiological Extranodal Extension Detected by Computed Tomography for Predicting Outcomes in Patients With Locally Advanced Head and Neck Squamous Cell Cancer Treated With Radical Concurrent Chemoradiotherapy.

Objective: Extra Nodal Extension (ENE) assessment in locally advanced head and neck cancers (LAHNCC) treated with concurrent chemo radiotherapy (CCRT) is challenging and hence the American Joint Committee on Cancer (AJCC) N staging. We hypothesized that radiology-based ENE (rENE) may directly impact outcomes in LAHNSCC treated with radical CCRT. Materials and Methods: Open-label, investigator-initiated, randomized controlled trial (RCT) (2012-2018), which included LAHNSCC planned for CCRT. Patients were randomized 1:1 to radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2) [cisplatin radiation arm (CRT)] or same schedule of CRT with weekly nimotuzumab (200 mg) [nimotuzumab plus CRT (NCRT)]. A total of 536 patients were accrued and 182 were excluded due to the non-availability of Digital Imaging and Communications in Medicine (DICOM) computed tomography (CT) data. A total of 354 patients were analyzed for rENE. Metastatic nodes were evaluated based on five criteria and further classified as rENE as positive/negative based on three-criteria capsule irregularity with fat stranding, fat invasion, and muscle/vessel invasion. We evaluated the association of rENE and disease-free survival (DFS), loco-regional recurrence-free survival (LRRFS), and overall survival (OS). Results: A total of 244 (68.9%) patients had radiologically metastatic nodes (rN), out of which 140 (57.3%) had rENE. Distribution of rENE was balanced in the two study groups CRT or NCRT (p-value 0.412). The median follow-up period was 39 months (ranging from 35.5 to 42.8 months). Complete response (CR) was seen in 204 (57.6%); incomplete response (IR), i.e., partial response plus stable disease (PR + SD), in 126 (35.6%); and progressive disease (PD) in 24 (6.8%). rENE-positive group had poor survival compared to rENE-negative group 3-year OS (46.7% vs. 63.6%), poor DFS (48.8% vs. 87%), and LRRFS (39.9% vs. 60.4%). rENE positive had 1.71 times increased risk of IR than rENE negative. Overall stage, site, clinical metastatic node (cN), response, and rENE were the significant factors for predicting OS, DFS, and LRRFS on univariate analysis. After making adjustment on multivariate analysis, rENE was an independent prognostic factor for DFS and trending to be significant for OS. Conclusion: Pre-treatment rENE is an independent prognostic marker for survival in patients with LAHNSCC treated radically with CCRT that can be used as a potential predictive marker for response to treatment and hence stratify patients into responders vs. non-responders. We propose the mahajan rENE grading system applicable on CT, magnetic resonance imaging, positron emission tomography-contrast-enhanced CT, and ultrasound.

Seeing Is Not Believing: Intraoperative Nerve Monitoring (IONM) in the Thyroid Surgery.

Ensuring the integrity of the recurrent laryngeal nerve (RLN), the external branch of superior laryngeal nerve (EBSLN) and preservation of normal voice are the prime 'functional' goals of thyroid surgery. More in-depth knowledge of neuronal mechanisms has revealed that anatomical integrity does not always translate into functional integrity. Despite meticulous dissection, neural injuries are not always predictable or visually evident. Intraoperative nerve monitoring (IONM) is designed to aid in nerve identification and early detection of functional impairment. With the evolution of technique, intermittent monitoring has given way to continuous-IONM. Over the years, IONM gathered both support and flak. Despite numerous randomised studies, systematic reviews, and meta-analyses, there still prevails a state of clinical equipoise concerning the utility of IONM and its cost-effectiveness. This article inspects the true usefulness of IONM, elaborates on the optimal way to practice it, and presents a critical literature review.

Surgical Site Infections in patients undergoing major oncological surgery during the COVID-19 paNdemic (SCION): A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. METHODS: Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. RESULTS: There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. CONCLUSION: Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.

Prospective Phase II Open-Label Randomized Controlled Trial to Compare Mandibular Preservation in Upfront Surgery With Neoadjuvant Chemotherapy Followed by Surgery in Operable Oral Cavity Cancer.

PURPOSE: The objective of this study was to explore the potential role and safety of neoadjuvant chemotherapy (NACT) in tumor shrinkage and resultant mandibular preservation in oral cancers compared with conventional surgical treatment. METHODS: This study was a single-center, randomized, phase II trial of treatment-naive histologically confirmed squamous cell carcinoma of the oral cavity with cT2-T4 and N0/N+, M0 (American Joint Committee on Cancer, seventh edition) stage, necessitating resection of the mandible for paramandibular disease in the absence of clinicoradiologic evidence of bone erosion. The patients were randomly assigned (1:1) to either upfront surgery (segmental resection) followed by adjuvant treatment (standard arm [SA]) or two cycles of NACT (docetaxel, cisplatin, and fluorouracil) at 3-week intervals (intervention arm [IA]), followed by surgery dictated by postchemotherapy disease extent. All patients in the IA received adjuvant chemoradiotherapy, and patients in the SA were treated as per final histopathology report. The primary end point was mandible preservation rate. The secondary end points were disease-free survival and treatment-related toxicity. RESULTS: Sixty-eight patients were enrolled over 3 years and randomly assigned to either SA (34 patients) or IA (34 patients). The median follow-up was 3.6 years (interquartile range, 0.95-7.05 years). Mandibular preservation was achieved in 16 of 34 patients (47% [95% CI, 31.49 to 63.24]) in the IA. The disease-free survival (P = .715, hazard ratio 0.911 [95% CI, 0.516 to 1.607]) and overall survival (P = .747, hazard ratio 0.899 [95% CI, 0.510 to 1.587]) were similar in both the arms. Complications were similar in both arms, but chemotherapy-induced toxicity was observed in the majority of patients (grade III: 14, 41.2%; grade IV: 11, 32.4%) in the IA. CONCLUSION: NACT plays a potential role in mandibular preservation in oral cancers with acceptable toxicities and no compromise in survival. However, this needs to be validated in a larger phase III randomized trial.

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.

Intensity-modulated radiation therapy for nasal cavity and paranasal sinus tumors: Experience from a single institute.

BACKGROUND: To assess the efficacy of intensity-modulated radiation therapy (IMRT) for tumors of the nasal cavity and paranasal sinus (PNS) region. MATERIALS AND METHODS: Two hundred fourteen patients with tumors of the nasal cavity and PNS region treated with curative intent IMRT between 2007 and 2019 were included in this retrospective analysis. RESULTS: Fifty-one (24.1%) received definitive RT/CTRT and 163 (75.9%) received adjuvant RT. Most common histology was squamous cell carcinoma (26.1%) followed by adenoid cystic carcinoma (21.5%). The median follow-up was 43.5 months. The 5-year local control (LC), event-free survival (EFS), and overall survival (OS) for the entire cohort was 66.9%, 59%, and 73.9%, respectively. On univariate analysis treatment with nonsurgical modality, T classification and undifferentiated/poorly differentiated histology were associated with inferior 5-year LC, EFS, and OS. Four patients had late Grade 3/Grade 4 ocular toxicity. CONCLUSIONS: IMRT should be the standard of care for tumors of PNS region across all histologies and treatment setting.

Prognostic Impact of Pattern of Mandibular Involvement in Gingivo-Buccal Complex Squamous Cell Carcinomas: Marrow and Mandibular Canal Staging System.

Purpose: To study the pattern of mandibular involvement and its impact on oncologic outcomes in patients with gingivo-buccal complex squamous cell carcinoma (GBC-SCC) and propose a staging system based on the pattern of bone involvement (MMC: Marrow and mandibular canal staging system) and compare its performance with the 8th edition of the American Joint Committee on Cancer (AJCC8). Methods: This retrospective observational study included treatment-naïve GBC-SCC patients who underwent preoperative computed tomography (CT) imaging between January 1, 2012, and March 31, 2016, at a tertiary care cancer center. Patients with T4b disease with high infratemporal fossa involvement, maxillary erosion, and follow-up of less than a year were excluded. The chi-square or Fisher's exact test was used for descriptive analysis. Kaplan-Meier estimate and log-rank test were performed for survival analysis. Multivariate analysis was done using Cox regression analysis after making adjustments for other prognostic factors. p-Value <0.05 was considered as significant. Based upon the survival analysis with different patterns of bone invasion, a new staging system was proposed "MMC: Marrow and mandibular canal staging system". "Akaike information criterion" (AIC) was used to study the relative fitted model of the various staging (TNM staging-AJCC8) with respect to survival parameters. Results: A total of 1,200 patients were screened; 303 patients were included in the study. On radiology review, mandibular bone was involved in 62% of patients. The pattern of bone involvement was as follows: deep cortical bone erosion (DCBE) in 23%, marrow in 34%, and marrow with the mandibular canal in 43% of patients. Patients with DCBE and no bone involvement (including superficial cortical) had similar survival [disease-free survival (DFS) and locoregional recurrence-free survival (LRRFS)], and this was significantly better than those with marrow with or without mandibular canal involvement (for both DFS and LRRFS). Patients with DCBE were staged using the MMC, and when compared with the AJCC8, the MMC system was better for the prediction of survival outcomes, as AIC values were lower compared with those of the AJCC8. There was a significant association (p = 0.013) between the type of bone involvement and the pattern of recurrence. Conclusions: For GBC-SCC, only marrow with or without mandibular canal involvement is associated with poorer survival outcomes. As compared with the AJCC8, the proposed Mahajan et al. MMC staging system downstages DCBE correlates better with survival outcomes.

Evaluation and validation of Physiological and Operative Severity Score for the enumeration of mortality and morbidity and Portsmouth-POSSUM scores in predicting morbidity and mortality in patients undergoing head and neck cancer surgeries.

BACKGROUND: Identification of risk factors for perioperative complications helps in the prognostication. We wanted to determine whether Physiological and Operative Severity Score for the enumeration of mortality and morbidity (POSSUM) and Portsmouth-POSSUM (P-POSSUM) can be used in patients undergoing head and neck oncosurgery. METHODS: We conducted a retrospective analysis of 1265 patients after they had major head and neck oncosurgeries. Demographic, surgical and outcome data was collected. We separately analyzed data for patients who had undergone cancer surgery for oral cavity, pharynx, and larynx. We calculated the POSSUM and P-POSSUM scores. RESULTS: POSSUM scoring system had moderate discrimination (AUC = 0.61) and good calibration (P = .36) for the entire study cohort and in the subgroup. Since there were no deaths in the entire cohort, we were not able to check predictive ability of the scores, for mortality. CONCLUSIONS: We found that POSSUM had moderate discrimination and good calibration for morbidity prediction in head and neck cancer surgeries, as well as for the selected subgroup.

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane-based induction chemotherapy and concurrent chemo-radiotherapy in the modern era.

OBJECTIVE: To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center. METHODS: We retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with "risk-adapted" intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow up of 45 months (range: 8-113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications. CONCLUSIONS: Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.

Management of the neck in oral cancers.

Oral cavity cancers are treated by surgery with or without adjuvant therapy. Being the most important prognostic factor, neck node management is an important aspect of treating oral cancers. There are numerous areas of debate in the management of the node-negative and node-positive neck. In an attempt to answer these questions, a large volume of literature has been generated over the last few decades. This review article describes the current evidence and approach considerations for the management of cervical nodes in patients with oral cavity cancers.