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.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

The significance of the presence of extranodal extension in the metastatic node of differentiated thyroid cancer: a proposal for modification in the American Thyroid Association (ATA) risk stratification.

BACKGROUND: Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. METHODOLOGY: Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. RESULTS: Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2-3 cm without ENE, 0.2-3 cm with ENE and > 3 cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. CONCLUSIONS: Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

Real world data on long term outcome of neoadjuvant chemotherapy in locally advanced esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation - Results from a single centre study.

INTRODUCTION: Esthesioneuroblastoma and sinonasal neuroendocrine carcinoma (SNEC) are the most common histological subtypes of non-squamous Sinonasal Tumors. A multidisciplinary approach is preferred for locally advanced unresectable esthesioneuroblastoma and SNEC. METHODS: From June 2010 to October 2021, 59 patients with esthesioneuroblastoma and SNEC received NACT. NACT consists of 2-3 cycles of Etoposide-Platinum based chemotherapy. Depending upon response and performance status, subsequent therapy was planned. SPSS descriptive statistics were performed for analysis. Kaplan Meir methods were used for the estimation of Progression Free Survival (PFS) and Overall Survival (OS). RESULTS: 45 (76.3 %) Esthesioneuroblastoma and 14 (23.7 %) SNEC patients received NACT. The median age of the population was 45 years (range 20-81 years). The majority of patients received 2-3 cycles of Platinum (Cisplatin or Carboplatin) + Etoposide as NACT. 28 patients (47.5%) underwent surgery and 20 patients (33.9%) received definitive chemoradiotherapy after NACT. The most common grade 3 or above adverse events were anemia (13.6%), neutropenia (27.1), and hyponatremia (45.8%). At the time of analysis, the median PFS was 56 months (95% CI 31 months to 77 months), and the median OS was 70 months (95% CI 56 months to 86 months). The most common late toxicities noticed were metabolic syndrome (42.4%), hyperglycemia (39%), nasal bleeding (33.9%), hypertension (17%), dyslipidemia (8.5%), and hypothyroidism (5.1%). CONCLUSION: The study shows that NACT is safe, and can be easily delivered without any life-threatening toxicities, with a favorable response and improved survival in this subset of patients.

Neoadjuvant chemotherapy in a rare type of very locally advanced sinonasal carcinomas - long-term results from a tertiary care centre.

Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.

Impact of surgical site infection on unplanned hospital readmissions, initiation of adjuvant treatment following surgery, and disease-free survival on patients with upper aerodigestive tract squamous cell carcinoma.

INTRODUCTION: Unplanned hospital readmission (UHR) is an important indicator of the quality of the healthcare system in place. It has various implications for the patients and the healthcare system at large. In this article, we have attempted to understand the various factors influencing UHR and the start of adjuvant treatment following cancer surgery. PATIENTS & METHODS: In this study adult patients above 18 years of age with upper aerodigestive tract squamous cell carcinoma who underwent surgery at our center between July 2019 to December 2019 were included in the study. Various factors influencing UHR and delay in receiving adjuvant treatment were analyzed. RESULTS: A total of 245 patients satisfied the inclusion criteria. Surgical site infection (SSI) was the factor that had the maximum influence on the UHR (p < 0.002, OR: 5.6, 95% CI: [1.911-16.4]) and delaying the start of adjuvant treatment (p = 0.008, OR: 3.786, 95% CI: [1.421-10.086]) on multivariate analysis. Surgery lasting for >4 h and patients who had received prior treatment tended to develop SSI postoperatively. The presence of SSI also seemed to have had a negative influence on disease-free survival (DFS) as well. CONCLUSIONS: SSI is an important postoperative complication having major implications in terms of increased UHR and delays in starting adjuvant treatment which in turn is reflected as a poorer DFS among patients who develop SSI postoperatively.

Assessing the Agreement Between Preoperative Fine-Needle Aspiration Cytology (FNAC) Done for Major Salivary Gland Neoplasm When Reported by Head and Neck Pathologists and Non-head and Neck Pathologists with Its Final Histopathology.

The preoperative FNA is an important investigation in the workup of a salivary gland pathology. A preoperative diagnosis is important to plan management and counsel patients accordingly. In this study, we aimed to assess the agreement between the preoperative FNA and the final histopathology report when reported by a head and neck and a non-head and neck pathologist. All patients with major salivary gland neoplasm having undergone a preoperative FNA before surgery from January 2012 to December 2019 at our hospital were included in the study. Analysis was done to check for concordance between head and neck and non-head and neck pathologists of the preoperative FNA and final histopathology. Three hundred and twenty-five patients were included in the study. The preoperative FNA could identify the tumour as benign or malignant in the majority (n = 228, 70.1%). The agreement between the preoperative FNA, frozen section diagnosis and the reporting of grade in the frozen section and the final HPR was slightly better with the head and neck pathologist (kappa = 0.429, kappa = 0.698 and kappa = 0.257), respectively, than with the non-head and neck pathologist (kappa = 0.387, kappa = 0.519 and kappa = 0.158), all of which was statistically significant (p < 0.001). The diagnosis made with the preoperative FNA and reporting in the frozen section had a fair agreement with the final histopathology when reported by a head and neck pathologist in comparison to a non-head and neck pathologist.

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.

National Cancer Grid Virtual Tumor Boards of Head and Neck Cancers: An Innovative Approach to Multidisciplinary Care.

PURPOSE: Virtual tumor board (VTB) via videoconference facility involving multiple specialists in the decision making for various tumors is well accepted, especially in high-income countries. Information on virtual tumor boards for head and neck cancers especially from low- and middle-income countries is sparse. In this study, we have audited the findings of the National Cancer Grid VTBs performed for head and neck cancers. METHODS: All patients discussed in the head and neck VTBs at our center between December 2016 and February 2022 were included in the study. Details such as the type of institute sending patients for discussion, its location, subsites within the head and neck region, histopathology, treatment setting or question for the VTB, and availability of guidelines for such patient scenarios were assessed. Also, a survey was sent to assess the usefulness of the VTBs. RESULTS: A total of 208 patients were discussed in 54 VTB sessions. The most common head and neck sites discussed in the VTBs were the oral cavity (n = 64, 30.7%) followed by skull base/nose and paranasal sinuses/eyelid-orbit tumors (n = 49, 23.5%). Nonsquamous cell carcinoma was the most common histopathology discussed; recurrent cancers/residual diseases were the most common treatment settings (n = 134, 64.4%) for which there were no existing guidelines. Survey results showed that most VTB decisions were implementable, and respondents felt that VTBs were a useful educational tool as well. CONCLUSION: Our study affirms the feasibility of VTBs in low- and middle-income countries' health care systems for managing uncommon malignancies and clinical situations, which act as an important educational platform.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Impact of Changes in Treatment Paradigms on Survival in Oral Squamous Carcinoma-a Population-Level Study.

There have been notable improvements in the treatment of oral cancers. The objective of this study was to see whether these improvements have translated into survival benefits at the population level from the SEER database. This is a retrospective study using the SEER 19 Custom database which included patients diagnosed with oral cancer between January 1, 1995, and December 31, 2015. The overall stage, age, sex, and treatment modalities were the covariates. For analysis, the patients were divided into four cohorts as per their year of diagnosis-cohort I included patients who were diagnosed between 1995 and 2000 (n = 3873), cohort II between 2001 and 2005 (n = 5881), cohort III between 2006 and 2010 (n = 6233), and cohort IV between 2011 and 2015 (n = 12567). Patients undergoing surgery with adjuvant therapy have increased significantly across cohorts and there is a significant fall in patients undergoing non-surgical treatment. Pairwise comparison by the Mantel-Cox test showed that cohort IV had significantly improved median overall survival (OS) and disease-specific survival (DSS) as compared to other cohorts and there was a significant impact of treatment modality on OS and DSS, especially in cohorts III and IV (p<0.001). Though geographical variations in the presentation and habits limit the generalization of these results, this study demonstrates that the changes and improvements in treatment paradigms incorporating level I evidence and surgical techniques have translated into improved survival outcomes at the population level. We recommend further studies on the local population to lend further credence to our observation. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01790-0.

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.

Incidence and impact of skip metastasis in the neck in early oral cancer: Reality or a myth?

OBJECTIVES: Varying evidence exists surrounding skip metastasis in clinically node-negative oral cancer. We aim to report its incidence, identify factors predicting its presence, and determine survival outcomes to possibly decide "adequacy" of neck dissection for this select group. METHODS: A review of audit records (clinical and pathologic) was undertaken to identify early stage (cT1/T2 cN0) oral squamous carcinoma patients operated between January 2016 and December 2020. Skip metastasis was defined as presence of nodal metastases distant from the primary tumour and at a lower level without metastases at levels above this. The factors predicting its presence were determined using chi-square and multivariate tests. Survival analysis was performed using Kaplan-Meier and regression hazard models. RESULTS: Occult metastasis rate was 17.9 % among 761 patients, with 47.1 % travelling to level I. Skip metastasis at level III was seen in 1.2 % and level IV was 0.3 %. Presence of PNI predicted the presence of skip metastasis at level III (p = 0.041, OR-0.241, 95 %CI 0.062-0.942) and no significant factors were identified for level IV. The 5-year disease-free survival was significantly reduced with isolated level IV metastasis (50 % vs 79.6 %, p = 0.017). Isolated occult metastasis at level Ia was in 0.3 %, all from tongue cancers. Their presence did not impact the 5-year overall survival (100 % vs 90.7 %, p = 0.628) and disease-specific survival (100 % vs 92.5 %, p = 0.675). CONCLUSION: The negligible incidence of skip metastasis to level IV in a clinically node negative neck suggests that clearance up to level III might be adequate in a large majority of patients.

Diagnostic and prognostic role of protein and ultrastructural alterations at cell-extracellular matrix junctions in neoplastic progression of human oral malignancy.

Despite advancements in technology and increase in favorable outcomes associated with oral cancer, early detection remains the most significant factor in limiting mortality. The current study aimed to develop early diagnostic and prognostic markers for oral tumorigenesis. Protein and ultrastructural alterations at cell-extracellular matrix (ECM) adhesion junctions were examined concurrently using immunohistochemistry (IHC) and transmission electron microscopy (TEM) on progressive grade of oral carcinomas (n = 285). The expression of hemidesmosome (HD) proteins-integrin ß4, BP180, and laminin-5 increased in hyperplasia as compared to normal, and significantly increased further, as the disease progressed. TEM analysis in parallel tissues revealed a significant decrease in HD number and increase in the length of basal lamina (BL) in hyperplasia. With cancer progression, the severity of ultrastructural alterations increased gradually and significantly. Overexpression of HD proteins, decrease in HD number and increase in BL length significantly correlated with nodal metastasis, local recurrence, and recurrence-free survival of patients. Concurrent use of IHC and TEM can add value to early recognition of neoplastic changes in primary carcinomas of oral cavity. In this regard, altered expression of integrin ß4 and laminin-5, loss of HDs, and increased BL length could offer criteria for early diagnosis and prognosis of oral malignancy.

Regression Derived Staging Model to Predict Overall and Disease Specific Survival in Patients With Major Salivary Gland Carcinomas With Independent External Validation.

PURPOSE: The current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally. MATERIALS AND METHODS: From SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into "Low Aggression" and "High aggression" groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019. RESULTS: Six thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients. CONCLUSION: We propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.

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.

Parotid fistula and/or salivary collection: an underrecognized and underreported preventable complication following surgery for oral cancer.

BACKGROUND: Parotid fistula after surgery for oral cancer is a less commonly recognized and less reported complication. In this study, we aimed to report its incidence and identify factors predisposing patients to it and the management of the patients in our cohort. METHODS: This was a retrospective study of treatment-naive patients with oral cancer who underwent surgery from January 2019 to December 2020 in a single unit of our institute. Patients who were operated for recurrence and second primary were excluded. RESULTS: A total of 434 patients were included in the study. Most were men (n = 352; 81.1%) and presented with an advanced clinical stage (n = 318; 73.2%). The incidence of parotid fistula in our study was 6.9% (n = 30 of 434). Buccal mucosa/gingival buccal sulcus subsite (P = .05; odds ratio [OR] = 3.423; 95% CI, 0.969-12.087) and advanced clinical T stage (P = .003; OR = 6.15; 95% CI, 1.835-20.608) were the 2 most important factors predisposing patients to the development of parotid fistula after surgery for oral cancer. CONCLUSIONS: Parotid fistula is a less common complication after surgery for oral cancer. A conservative treatment approach is usually successful in treating this complication.