Evaluation of Metronomic Therapy as a Low-Cost, Sustainable, Standard-of-Care Option in Desmoid Fibromatosis: Real-World Data From a Tertiary Care Center in India.

PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Performance of potentially inappropriate medications assessment tools in older Indian patients with cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) use are common problems in older adults. Safe prescription practices are a necessity. The tools employed for the identification of PIM sometimes do not concur with each other. METHODS: A retrospective analysis of patients ≥60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India from 2018 to 2021 was performed. Beer's-2015, STOPP/START criteria v2, PRISCUS-2010, Fit fOR The Aged (FORTA)-2018, and the EU(7)-PIM list-2015 were the tools used to assess PIM. Every patient was assigned a standardized PIM value (SPV) for each scale, which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all five tools was considered the reference standard for each patient. Bland-Altman plots were utilized to determine agreement between each scale and the reference. Association between baseline variables and PIM use was determined using multiple logistic regression analysis. RESULTS: Of the 467 patients included in this analysis, there were 372 (79.66%) males and 95 (20.34%) females with an average age of 70 ± 5.91 years. The EU(7)-PIM list was found to have the highest level of agreement given by a bias estimate of 0.010, the lowest compared to any other scale. The 95% CI of the bias was in the narrow range of -0.001 to 0.022, demonstrating the precision of the estimate. In comparison, the bias (95%) CI of Beer's criteria, STOPP/START criteria, PRISCUS list, and FORTA list were -0.039 (-0.053 to -0.025), 0.076 (0.060 to 0.092), 0.035 (0.021 to 0.049), and -0.148 (-0.165 to -0.130), respectively. Patients on polypharmacy had significantly higher PIM use compared to those without (OR = 1.47 (1.33-1.63), p = <0.001). CONCLUSIONS: The EU(7)-PIM list was found to have the least bias and hence can be considered the most reliable among all other tools studied.

Response assessment of post-treatment head and neck cancers to determine further management using NI-RADS (Neck Imaging Reporting and Data System): a subgroup analysis of a randomized controlled trial.

Objective: Interpreting complex post-treatment changes in head and neck cancer (HNC) is challenging with further added perplexity due to variable interobserver interpretation and hence evolved the NI-RADS lexicon. We evaluated the accuracy of NI-RADS in predicting disease status on 1st post-treatment follow-up CECT in a homogenous cohort of those who received only chemoradiation. Methods: Retrospective analysis of imaging was done for LASHNC patients who received radical chemoradiation in an open-label, investigator-initiated, phase 3 randomized trial (2012-2018) randomly assigned to either radical radiotherapy with concurrent weekly cisplatin (CRT) or CRT with the same schedule plus weekly nimotuzumab (NCRT). 536 patients were accrued, and 74 patients who did not undergo PET/CECT after 8 weeks post-CRT were excluded. After assessing 462 patients for eligibility to allocate NI-RADS at primary and node sites, 435 cases fell in the Primary disease cohort and 412 cases in the Node disease cohort. We evaluated sensitivity, disease prevalence, the positive and negative predictive value of the NI-RADS lexicon, and accuracy, which were expressed as percentages. We also prepared flow charts to determine concordance with allocated NI-RADS category and established accuracy with which it can identify disease status. Results: Out of 435 primary disease cohort, 92%, 55%, 48%,70% were concordant and had 100%, 72%, 70%, 82% accuracy in NI-RADS1 (n=12), NI-RADS2 (n=261), NIRADS3 (n=105), and NI-RADS 4 (n=60) respectively. Out of 412 nodes disease cohort, 95%, 90%, 48%, 70%were concordant and had 92%, 97%, 90%, 67% accuracy in NI-RADS1 (n=57), NI-RADS2 (n=255), NI-RADS3 (n=105) and NI-RADS4 (n=60) respectively. % concordance of PET/CT and CECT across all primary and node disease cohorts revealed that PET/CT was 91% concordant in primary NI-RADS2 as compared to 55% concordance of CECT whereas concordance of CECT was better with 57% in primary NI-RADS3 cohort as compared to PET/CT concordance of 41%. Conclusion: The accuracy with which the NI-RADS lexicon performed in our study at node sites was better than that at the primary site. There is a great scope of research to understand if CECT performs better over clinical disease status in NI-RADS 3 and 4 categories. Further research should be carried out to understand if PET/CECT can be used for close interval follow-up in stage III/IV NI-RADS 2 cases.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

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.

Translation and Validation of COST - FACIT (Version 2) Questionnaire into Hindi and Marathi to Assess Financial Toxicity in Indian Cancer Patients.

Amit JoshiBackground Cancer is one of the most expensive and exhaustive medical conditions with a huge impact on the financial condition of the patient and their family members. A lot of advancements have led to improvement in the survival of the patients but at a raised cost. Comprehensive Score for financial Toxicity - Functional Assessment of Chronic Illness Therapy (COST - FACIT Version 2) is one such validated and widely used tool. Assessing the financial burden in our country is still far more challenging as COST - FACIT is available in the English language but not in any regional language. Hence, we decided to validate this tool in Hindi and Marathi languages. Material and Methods A single-center, cross-sectional study was conducted in the Department of Uro-Oncology at the Tata Memorial Hospital. The original version of the COST - FACIT (Version 2) was translated from English into Hindi and Marathi languages, following the FACIT translation method and tested for content validity that included two forward translations, followed by reconciliation and a backward translation. The questionnaires were then approved by the FACIT team, and pilot testing was done for 20 patients (10 for each Hindi and Marathi language). Each of these 20 patients, after filling up the questionnaire themselves, was interviewed for any difficulty encountered during answering the questionnaire. Based on the suggestions or interpretations of this pilot testing, the necessary changes were incorporated in the final Hindi and Marathi questionnaires. Results A total of 20 patients (10 each for Hindi and Marathi) were included for pilot testing of the questionnaire. The median age of the entire cohort was 61 years (27-79). The questionnaires showed good content and face validity and demonstrated a high internal consistency (Cronbach's α: 0.85 for Hindi, 0.89 for Marathi). Conclusion The questionnaire COST - FACIT (Version 2) has been approved and validated in Hindi and Marathi languages by the FACIT team for use in clinical practice and studies.

Caregiver burden in older Indian patients with cancer- Experience from a tertiary care center.

INTRODUCTION: Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer. MATERIALS AND METHODS: This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis. RESULTS: Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60-90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6-20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level. DISCUSSION: Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden.

G8 and VES-13 as screening tools for geriatric assessment and predictors of survival in older Indian patients with cancer.

BACKGROUND: Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are quick and easy-to-use screening tools, developed and validated in older patients living in North America and Europe for predicting abnormalities in the subsequent geriatric assessment. The applicability of these screening tools in older Indian patients with cancer is not known. METHODS: An observational study in 308 Indian patients with cancer aged ≥60 years, who were evaluated in the Geriatric Oncology clinic at the Tata Memorial Hospital, Mumbai, India, between June 2018 and November 2020. Patients underwent the G8 and VES-13 screening tools followed by a geriatric assessment. The objectives were to determine the diagnostic accuracy of the G8/VES-13 screening tools to detect an abnormal geriatric assessment, to determine their association with the Eastern Cooperative Oncology Group (ECOG) performance status (PS)/Cancer Aging and Research Group (CARG) scores, to determine the optimal cut-off value on the G8 scale for older Indian patients with cancer, and to determine whether an abnormal G8/VES-13 score was associated with shorter survival. We also aimed to assess the utility of combining the G8 and VES-13 scores to predict for an abnormal geriatric assessment and poorer survival. RESULTS: The sensitivity and specificity of the G8 (cut-off, ≤14) score were 84.4% and 17.6%, respectively, whereas those for the VES-13 score (≥3) were 34.9% and 82.4%, respectively. The appropriate abnormal G8 cut-off score was noted to be 12. Abnormal G8 (≤14) and VES-13 scores were not associated with an abnormal subsequent geriatric assessment [p = 0.736 (G8)], while abnormal G8 (≤14) scores did not predict for worse survival outcomes. Lowering the cut-off of the G8 score to <12 and/or combining an abnormal G8 (<12) with the VES-13 score were found to be associated with an abnormal subsequent geriatric assessment [p < 0.001 (G8), p < 0.001(G8 + VES-13)] and predicted for worse survival. CONCLUSIONS: An abnormal G8 cut-off score < 12 is therefore appropriate in older Indian patients with cancer. G8 < 12 predicts for the presence of non-oncological vulnerabilities and shorter survival. Lowering the cutoff of G8 to 12translated to a 35% reduction in the number of patients undergoing a complete geriatric assessment. Combined with VES-13, the G8 can be reliably used to identify those patients who would benefit the most from a geriatric assessment and help in optimal resource utilization especially in busy Indian centers.

Incremental value of endoscopic brush cytology in response assessment after chemo-irradiation for Esophageal cancer.

BACKGROUND: Response assessment after chemo-radiotherapy (CTRT) in locally advanced esophageal cancer is usually performed using a PET-CT scan, an upper GI endoscopy (UGIE) and histological correlation with biopsy or cytology. We aim to study the incremental value of brush cytology in addition to PET-CT for response assessment. MATERIALS AND METHODS: In this retrospective analysis, 40 patients with Stage II- IV carcinoma esophagus treated with radical intent between June 2015 and August 2019 were included. Patients were treated with either upfront concurrent CTRT or neo-adjuvant chemotherapy followed by CTRT. All patients underwent PET-CT and UGIE for initial staging and response assessment on follow-up. Patients with esophageal stricture (disease related or treatment induced) had brush cytology done during UGIE. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of brush cytology were calculated considering serial clinical follow-up as gold standard. RESULTS: Twenty-three male (57.5%) and 17 (42.5%) female patients with median age of 57 years (range: 27 - 79 years) were analyzed. Concurrent CTRT was delivered in 52.5%; 75% patients were treated with intensity-modulated radiotherapy (IMRT); median RT dose was 63 Gy (range- 41.4 to 64 Gy). At a median follow-up of 16 months (range 6- 54 months), 20 patients (55.5%) were clinically controlled, 9 (25%) had local recurrence, 5 (13.8%) had loco-regional recurrence and 2 had distant metastasis. Considering clinical follow-up as the gold standard, sensitivity, PPV and NPV of PET-CT combined with brush cytology improved compared to PET-CT alone and was found to be 75%, 90%, 85.7% and 81.8% respectively. CONCLUSION: We found that brush cytology on endoscopy is a simple tool with high specificity which adds value to the findings of response assessment PET-CT scan and thereby can increase the confidence of the treating oncologist in making clinical decisions.

Primary mediastinal germ cell tumours with high prevalence of somatic malignancy: An experience from a single tertiary care oncology centre.

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

Validation of a novel causality assessment scale for adverse events in non-small cell lung carcinoma patients treated with platinum and pemetrexed doublet chemotherapy.

AIM: Accurate causality assessment (CA) of adverse events (AEs) is important in clinical research and routine clinical practice. The Naranjo scale (NS) used for CA lacks specificity, leading to a high rate of false positive causal associations. NS is a simple scale for CA; however, its limitations have reduced its popularity in favour of other scales. We therefore attempted to improvise the algorithm by addressing specific lacunae in NS. METHODS: We attempted to modify the existing NS by (a) changing the weightage given to certain responses, (b) achieving higher resolution to certain responses for delineating drug related and unrelated AEs and (c) modifying the slabs for classification of association as 'likely' and 'unlikely'. The new scale, named as the Sharma-Nookala-Gota (SNG) algorithm, was evaluated in a training set of 19 AEs in a tertiary care cancer hospital in western India, and further validated in a set of 104 AEs. Consensus of four physician opinion was taken as gold standard for comparison. RESULTS: Of the 19 AEs in the training set, 6 were described by the treating physician as 'not related' and 13 as related to the drug. The SNG algorithm had 100% concordance with physician opinion, whereas the NS had only 73.7% concordance. NS showed a tendency to misclassify AEs as 'related' when they were indeed 'not related'. In the validation set of 104 AEs, NS and SNG algorithms misclassified 30 and 2 AEs, respectively, leading to a concordance of 70.2% and 98.1%, respectively, with physician opinion. CONCLUSION: Decisive modifications of the NS resulted in the SNG scale, with superior specificity while retaining sensitivity against the gold standard. PLAIN LANGUAGE SUMMARY: SNG algorithm - A novel tool for causality assessment of adverse drug reactions Adverse events (AEs) can cause increased morbidity, hospitalisation, and even death. Hence it is essential to recognise AEs and to establish their correct causal relationship to a drug. Many causality assessment methods, scales and algorithms are available to assess the relationship between an AE and a drug. The Naranjo algorithm is most commonly employed in spite of its many drawbacks as it is simple to use. Concerns have been raised regarding the performance of the scale, and researchers have tried to answer them, but none of them could address all issues satisfactorily. We too experienced many problems while using it in our routine clinical practice and in clinical trials. For instance, the Naranjo scale is non-specific and shows a bias toward implicating the drug as the causal factor for AEs. This improper assessment has often led to drug discontinuation, thereby compromising the efficacy of treatment. Hence, we modified the existing Naranjo scale to a new one (the Sharma-Nookala-Gota - SNG algorithm) to address these shortcomings. We piloted the SNG causality assessment algorithm in patients suffering from AEs due to various drugs. The SNG algorithm was found to have good concordance with the physicians' assessment of causality. As a next step, we validated the SNG algorithm in patients receiving a standard drug combination of pemetrexed and carboplatin for lung cancer combination. Out of the 104 AEs observed in 65 patients, the SNG causality assessment algorithm showed good concordance (except in two cases) with the physicians' decision of causality assessment, while the Naranjo algorithm was not so successful. Hence, the SNG algorithm can be a better guide for causality assessment of AEs.

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma: an open-label, parallel-group, non-inferiority, randomised, phase 3 trial.

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1-3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings. METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18-70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0-1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m2 methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m2 intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed. FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6-12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615-0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7-12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4-9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616-0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01). INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible. FUNDING: Tata Memorial Center Research Administration Council. TRANSLATIONS: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.

Gender climate in Indian oncology: national survey report.

INTRODUCTION: There is evidence of under-representation of women in leadership roles and publications in oncology. However, there is little knowledge about their perceptions of professional environment, unique challenges and opportunities compared with male counterparts. The problem is more prominent in lower-income and middle-income countries like India and merits exploration. MATERIALS AND METHODS: A survey, 'Exploratory Study on the Challenges of Female Oncologists in India', was conducted among oncology professionals. We included questions on demography, working team details, role at work, perceived challenges for advancement of career, gender-related values brought into the team and the measures for improvement of gender disparity. Lead authorship data were collected from two Indian oncology journals. RESULTS: Of the 324 respondents, 198 (61.1%) were women. Majority of the respondents were medical oncologists (46.3%), ≤45 years old (69.4%) and working in universities and corporate hospitals (71.6%). One hundred eighty-nine (58.3%) respondents worked in teams with male majority, 50 (15.4%) in women-majority teams, while 85 (26.2%) worked in teams with gender equality. Of the 324 respondents, 218 (67.3%) had men managers, while 106 (32.7%) had women managers. Men led 160 (84.7%) male-majority teams; 45 (52.9%) gender-equal teams; and 13 (26%) female-majority teams (p<0.00001). Age >45 years was found to be associated with a leadership role (43% vs 25%, p=0.0012). The most significant barrier perceived for advancement of career for women was finding a work-life balance. Most respondents suggested provision of flexible training programmes to improve the disparity. Of the 558 journal publications inspected, 145 (26%) articles had a female first or corresponding author. CONCLUSIONS: The study brought out the current figures regarding gender climate in oncology practice and academia across India. We identified lead thrust areas and schemes to improve the gender bias. There needs to be action at international, national and personal levels to bring about an efficient gender-neutral workforce.

Metastatic or locally advanced mediastinal neuroendocrine tumours: outcome with 177Lu-DOTATATE-based peptide receptor radionuclide therapy and assessment of prognostic factors.

BACKGROUND: Primary neuroendocrine tumours (NETs) of mediastinum are unusual tumours with aggressive biological behaviour with limited treatment options and guarded prognosis. METHODS: Twenty-seven patients with histopathologically and radiologically proven metastatic or advanced mediastinal NET, who had undergone 177Lu-DOTATATE PRRT, were included in this retrospective analysis. Descriptive statistics was employed to calculate the cumulative overall survival (OS) and progression-free survival (PFS), determining correlation and strength of correlation between different variables with OS and PFS and finally, predictors of outcome (OS and PFS). RESULTS: In all 27 patients enrolled and analyzed, complete symptomatic response was observed in 10 patients (37%), partial response in seven patients (25.9%), symptomatically stable disease in four patients (14.8%), and symptoms progressed or worsened in six patients (22.2%). Metabolic response evaluation demonstrated complete metabolic response in one patient (3.7%), partial metabolic response was seen in nine patients (33.3%), metabolically stable disease was seen in five patients (18.5%), and 12 patients (44.4%) showed metabolic disease progression. None of the patients achieved complete anatomical/morphological response, six (22.2%) showed partial response, seven (25.9%) showed stable disease, and in 14 patients (51.9%), there was morphological disease progression. At the time of analysis, 10 patients (37%) succumbed to the disease. The median PFS was 36 months and the median OS was 66 months. Bivariate analysis showed significant level of association of PFS with surgical intervention, higher cumulative PRRT dose, metabolic response, smaller sized primary lesion, and low lesional FDG uptake. With regard to OS, higher cumulative PRRT dose, low FDG uptake and longer PFS showed significant association. CONCLUSION: Previous surgical intervention (including debulking surgery with R1 resection), higher cumulative dose of PRRT, and low FDG uptake of the tumour are associated with prolonged OS and PFS in patients with metastatic or advanced mediastinal NETs and were independent favourable prognostic markers.

Utility of response assessment PET-CT to predict residual disease in neck nodes: A comparison with the Histopathology.

OBJECTIVE: To assess the ability of Positron Emission Tomography-Computed Tomography (PET-CT) scans to detect residual disease in neck nodes with the Histopathology (HPR) as the gold standard. To obtain a Standardized Uptake Value max cutoff in these patients to predict residual disease in neck. METHODS: Head and neck squamous cell carcinoma patients who underwent Salvage neck dissection with or without primary site surgery post Concurrent Chemo-Radiotherapy (CCRT) during the period January 2008-December 2017 were included. All patients had response assessment PET-CT scan at 10-14 weeks. Agreement analysis was performed between PET-CT and HPR, fine needle aspiration cytology and HPR. Positive predictive value, Negative predictive value of PET-CT to detect residual neck nodal disease in comparison to HPR was analyzed. A Receiver Operating Characteristic (ROC) curve was plotted between the SUV max values and the HPR. A SUV max cutoff value was obtained from the ROC curve. RESULTS: A total of 75 patients were included. Thirty-one underwent salvage neck dissection along with surgery for primary disease and 45 underwent salvage neck dissection alone. PET-CT showed good agreement with the HPR to detect residual disease in neck nodes (Kappa=0.604). PET-CT had a PPV and NPV of 87.5% and 79.15% respectively as compared against the HPR. A SUV max cutoff of 4.62 had a specificity of 92.3% and sensitivity of 73.5% to detect residual disease in neck nodes on the HPR. CONCLUSION: PET-CT surveillance is an accepted treatment strategy. A neck node with SUV max of 4.62 and above is most likely to harbor residual nodal disease. LEVEL OF EVIDENCE: Level 2b.

CRE: a cost effective and rapid approach for PCR-mediated concatenation of KRAS and EGFR exons: Rapid way to detect EGFR and KRAS mutations.

Molecular diagnostics has changed the way lung cancer patients are treated worldwide. Of several different testing methods available, PCR followed by directed sequencing and amplification refractory mutation system (ARMS) are the two most commonly used diagnostic methods worldwide to detect mutations at  KRAS exon 2 and  EGFR kinase domain exons 18-21 in lung cancer. Compared to ARMS, the PCR followed by directed sequencing approach is relatively inexpensive but more cumbersome to perform. Moreover, with a limiting amount of genomic DNA from clinical formalin-fixed, paraffin-embedded (FFPE) specimens or fine biopsies of lung tumors, multiple rounds of PCR and sequencing reactions often get challenging. Here, we report a novel and cost-effective single multiplex-PCR based method, CRE (for  Co-amplification of five  K RAS and  E GFR exons), followed by concatenation of the PCR product as a single linear fragment for direct sequencing. CRE is a robust protocol that can be adapted for routine use in clinical diagnostics with reduced variability, cost and turnaround time requiring a minimal amount of template DNA extracted from FFPE or fresh frozen tumor samples. As a proof of principle, CRE is able to detect the activating  EGFR L858R and T790M  EGFR mutations in lung cancer cell line and primary tumors.