RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

RMAC study:A randomized study for evaluation of metronomic adjuvant chemotherapy in recurrent head and neck cancers post salvage surgical resection in those who are ineligible for re-irradiation

Background: Adjuvant re-chemoradiation after salvage surgery improves disease-free survival in recurrent head and neck cancer. However, most patients are ineligible for re-irradiation and are kept on observation. We investigated the efficacy of metronomic adjuvant chemotherapy (MAC) in this group of patients compared to observation. Methods: This was a randomized integrated phase II/III clinical trial. Adults with recurrent head and neck cancer, who had undergone salvage surgery, but were ineligible for adjuvant re-irradiation were randomized in a 1:1 ratio to either MAC arm or observation. MAC consisted of weekly oral methotrexate (at a dose of 15 mg per square meter of body surface area) and celecoxib (at a dose of 200 mg orally twice daily) for 6 months. The primary endpoint of phase 2 was disease-free survival (DFS) while that of phase 3 was overall survival (OS). For phase 2, to detect an improvement in the hazard ratio (HR) 0.67 with MAC, with a type 1 error of 10% (1-sided), type 2 error of 30%, 105 patients were required. While for phase 3, with a target HR of 0.77, with a type 1 error of 5%, type 2 error of 20%, 318 patients were required. Here we report the results of phase 2 part of the study. Results: At a median follow up of 30.2 months (95% confidence interval (CI), 25.3 to 35.1) the 1 year and 2-year DFS were 57.4% (95% CI, 42.8–69.5) and 37.6% (95% CI, 24.1–51) in MAC arm whereas the corresponding numbers were 62.3% (95% CI, 47.8 to 73.8) and 54.2%(95% CI, 39.8 to 66.5) in observation arm, respectively (hazard ratio for progression, 1.45; 95% CI, 0.87 to 2.47; P = 0.15). In the MAC arm, the 1 and 2 year OS was 78.7% (95% CI, 64.9 to 87.6) and 48% (95% CI, 34.1 to 62).The corresponding figures in the observation arm were 79.2% (95% CI, 65.7 to 87.9) and 65.5% (95% CI, 50.9 to 76.7) (hazard ratio for death, 1.7, 95% CI, 0.94 to 3.08; P = 0.08). Conclusion: The adjuvant 6-month metronomic schedule was ineffective in improving outcomes in recurrent head and neck cancers post salvage surgery who are ineligible for re-radiation. Trial registration. Clinical trial registry of India (CTRI)- CTRI/2016/04/006872 [Registered on 26/4/2016] © 2022 Elsevier Lt

A Neural Network Approach for Text Document Classification and Semantic Text Analytics

The nature of data that is being produced on a daily basis is vast and most amount of this data is in unstructured format. Hence, it is necessary to organize this data into different categories such that meaningful knowledge can be derived from such large volumes of data. The proposed methodology consists of a feature selection component and then a neural network classifier. The neural network system is trained against a large variety and of text document so that it can correctly predict the type of document presented as input. A machine learning algorithm is designed to select terms that will serve as basis to differentiate between various categories of topics. The algorithm will also analyse synonyms so that redundant type of information is kept under a same label

Extra-lymphatic filariasis at reconstructive surgery flap site recurrence of head and neck cancer

Filarial infection is commonly encountered in the Indian subcontinent. Here we present a clinical image of filarial infestation at the site of recurrence of head and neck cancer

Metronomic palliative chemotherapy in maxillary sinus tumor

Background: Metronomic chemotherapy consisting of methotrexate and celecoxib recently has shown promising results in multiple studies in head and neck cancers. However, these studies have not included patients with maxillary sinus primaries. Hence, the role of palliative metronomic chemotherapy in patients with maxillary sinus carcinoma that is not amenable to radical therapy is unknown. Methods: This was a retrospective analysis of carcinoma maxillary sinus patients who received palliative metronomic chemotherapy between August 2011 and August 2014. The demographic details, symptomatology, previous treatment details, indication for palliative chemotherapy, response to therapy, and overall survival (OS) details were extracted. SPSS version 16 was used for analysis. Descriptive statistics have been performed. Survival analysis was done by Kaplan-Meier method. Results: Five patients had received metronomic chemotherapy. The median age was 60 years (range 37-64 years). The proportion of patients surviving at 6 months, 12 months, and 18 months were 40%, 40%, and 20%, respectively. The estimated median OS was 126 days (95% confidence interval 0-299.9 days). The estimated median survival in patients with an event-free period after the last therapy of <6 months was 45 days, whereas it was 409 days in patients with an event-free period postlast therapy above 6 months (P = 0.063). Conclusion: Metronomic chemotherapy in carcinoma maxillary sinus holds promise. It has activity similar to that seen in head and neck cancers and needs to be evaluated further in a larger cohort of patients

A tertiary care experience with paclitaxel and cetuximab as palliative chemotherapy in platinum sensitive and nonsensitive in head and neck cancers

Background: The combination of paclitaxel and cetuximab (PaCe) has led to an encouraging response rate in Phase 2 setting with limited toxicity. The aim of our study was to assess the efficacy of this regimen in our setting in platinum sensitive and nonsensitive patients. Methods: This was a retrospective analysis of head and neck cancer patients treated with weekly PaCe as palliative chemotherapy between May 2010 and August 2014. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawal of patient's consent. The toxicity and response were noted in accordance with CTCAE version 4.02 and RECIST version 1.1 criteria, respectively. The response rates between platinum sensitive and nonsensitive patients were compared by Chi-square test. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan–Meier survival method and log-rank test was used for comparison. Cox proportional hazard model was used for identification of factors affecting PFS and OS. Results: One Hundred patients with a median age of 52 years (interquartile range: 46–56 years) were included. Forty-five patients (45%) were platinum insensitive, whereas 55 patients (55%) were platinum sensitive. In platinum insensitive patients and sensitive patients, the response rates were 38.5% and 22.2%, respectively (P = 0.104), whereas the symptomatic benefit in pain was seen in 89.5% and 71.7%, respectively (P = 0.044). The median PFS in platinum insensitive and sensitive patients were 150 and 152 days, respectively (P = 0.932), whereas the median OS was 256 days (95% confidence interval [95% CI]: 168.2–343.8 days) and 314 days (95% CI: 227.6–400.4 days), respectively (P = 0.23). Nineteen patients (19%) had grades 3–4 adverse events during chemotherapy. Conclusion: Weekly paclitaxel combined with cetuximab has promising efficacy and good tolerability in the palliative setting in advanced head and neck cancer in both platinum sensitive and insensitive patients