Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study.

Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / - intravenous (IV) pantoprazole. The primary endpoint in phase I was to determine the maximum safe dose of intravenous pantoprazole, whereas it was progression-free survival (PFS) in phase II. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov'18 and Oct'20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07-3.19) in the pantoprazole arm and 2.5 months (95% CI 2.04-3.81, HR, 1.14; 95% CI 0.78-1.66; P = 0.48) in the standard arm. Response rates were similar; pantoprazole arm 8.5%, standard arm 6.6%; P = 0.175. Overall survival was also similar; 5.6 months (95% CI 4.47-8.51) in the pantoprazole arm and 5.4 months (95% CI 3.48-8.54, HR 1.06; 95% CI 0.72-1.57; P = 0.75) in the standard arm. Grade ≥ 3 toxicities were similar. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.

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.

Second-line therapy in testicular germ cell tumours: results from a tertiary cancer care centre in India.

Background: Malignant testicular neoplasms constitute about 1% of all cancers in males. This is one of the most common tumours in adolescents and young adult males. After the introduction of cisplatin-based chemotherapy, the survival of germ cell tumour patients, even those with poor prognostic risk factors, has significantly improved over the years. Second-line chemotherapy in patients who have progressed over the first-line cisplatin-based chemotherapy has shown convincing 5 years of overall survival (OS). Methodology: This study is a retrospective analysis of testicular cancer patients from 2014 to 2020 who have received salvage chemotherapy treatment at Tata Memorial Centre. Patient demographics, tumour characteristics and treatment details were recorded in a specific format, and progression-free survival and OS were analysed along with response to therapy. Results: A total of 46 testicular cancer patients from 2014 to 2020, who received second-line chemotherapy, were analysed from the database maintained at our hospital. The median age at diagnosis was 29.5 (18-60) years. Most of the patients (30, 65.2%) presented with lung metastasis and 11 (23.9%) patients with liver metastasis. Most of the patients (21, 45.6%) received vinblastine, ifosfamide and cisplatin, whereas 13 (28.2%) patients received paclitaxel, ifosfamide and cisplatin regimen and 7 (15.2%) patients received GemOx regimen as the second-line chemotherapy. Median OS was observed to be 33.97 months and median progression-free survival was 29.01 months. Conclusion: Second-line chemotherapy in testicular germ cell tumours can result in long-term disease control and all patients who are fit to tolerate second-line therapy should be offered it. Patients with relapsed seminoma did better than relapsed non-seminomatous germ cell tumours.

Adaptation of the Patient Reported Outcome Measurement Information System (PROMIS) tool for childhood cancer in India: A qualitative study.

BACKGROUND: To fill the gap in patient-reported outcome (PRO) assessment in children with cancer in India, we planned to adapt domains from the HealthMeasures Patient Reported Outcomes Measurement Information System (PROMIS) tool. This study attempted to identify and pool outcomes relevant to children with cancer and their caregivers in Northern India. METHODS: The study was qualitative and conducted through focussed group discussions (FGDs) and in-depth interviews of children with cancer and their caregivers. Content analysis of transcripts from the sessions was done. The collected themes were collated with existing item banks of the PROMIS tool and new concepts unique to our population were compiled. RESULTS: A set of three FGDs and 14 interviews each for children and their caregivers were conducted. Following content analysis, 121 themes were identified including 10 new concepts. Themes pertaining to the physical domain were cited most. The theme distribution across the three domains was similar among children and caregivers. In the survivor cohort, the relative frequency of mention of psychological and social themes was higher compared to the whole cohort. Themes pertaining to mobility, cognitive dysfunction and peer relationships were more common among survivors. CONCLUSIONS: This qualitative study in children with cancer and their caregivers in India has facilitated a better understanding of the issues pertaining to cancer care that are of most importance to its stake holders. The themes collected may be used to formulate a PRO tool uniquely tailored for use in this population.

COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India.

Background: Surge of SARS CoV-2 infections ascribed to omicron variant began in December 2021 in New Delhi. We determined the infection and reinfection density in a cohort of health care workers (HCWs) along with vaccine effectiveness (VE) against symptomatic infection within omicron transmission period (considered from December 01, 2021 to February 25, 2022. Methods: This is an observational study from the All India Institute of Medical Sciences, New Delhi. Data were collected telephonically. Person-time at risk was counted from November 30, 2021 till date of infection/ reinfection, or date of interview. Comparison of clinical features and severity was done with previous pandemic periods. VE was estimated using test-negative case-control design [matched pairs (for age and sex)]. Vaccination status was compared and adjusted odds ratios (OR) were computed by conditional logistic regression. VE was estimated as (1-adjusted OR)X100-. Findings: 11474 HCWs participated in this study. The mean age was 36⋅2 (±10⋅7) years. Complete vaccination with two doses were reported by 9522 (83%) HCWs [8394 (88%) Covaxin and 1072 Covishield (11%)]. The incidence density of all infections and reinfection during the omicron transmission period was 34⋅8 [95% Confidence Interval (CI): 33⋅5-36⋅2] and 45⋅6 [95% CI: 42⋅9-48⋅5] per 10000 person days respectively. The infection was milder as compared to previous periods. VE was 52⋅5% (95% CI: 3⋅9-76⋅5, p = 0⋅036) for those who were tested within 14-60 days of receiving second dose and beyond this period (61-180 days), modest effect was observed. Interpretation: Almost one-fifth of HCWs were infected with SARS CoV-2 during omicron transmission period, with predominant mild spectrum of COVID-19 disease. Waning effects of vaccine protection were noted with increase in time intervals since vaccination. Funding: None.

Quality of life in patients with locally advanced head and neck squamous cell carcinoma undergoing concurrent chemoradiation with once-a-week versus once-every-3-weeks cisplatin.

INTRODUCTION: This trial was conducted to compare the efficacy of low dose once-a-week cisplatin and once-every-3-weeks cisplatin with radiation in locally advanced head and neck squamous cell carcinoma (LAHNSCC). The current analysis focuses on the quality of life (QoL) of patients in this trial. METHODS: In this phase III randomized trial, patients with nonmetastatic LAHNSCC were randomized to receive cisplatin 30 mg/m2 once-a-week or 100 mg/m2 once every- 3-weeks concurrently with radiotherapy. The primary endpoint was locoregional control. QoL was a key secondary endpoint. QoL was assessed using EORTC QLQ-C30 and QLQ-H&N35. QoL data were assessed at baseline, days 22 and 43 during treatment; and at 6, 12, 24 months. The linear mixed-effects model was used for longitudinal analysis of QoL to determine the impact of treatment (arm) and time on QoL. RESULTS: Three hundred patients were enrolled, data of 150 patients with available baseline QoL were analyzed. There was no significant difference in the global health status/QoL of the two treatment arms (p = 0.8664). There was no significant difference in the longitudinal QoL scores between the two treatment arms in all scales except constipation (p = 0.0096), less sexuality (p = 0.0002,), and financial difficulty (p = 0.0219). There was a worsening of the QoL scores in all scales in both arms during treatment, which improved after treatment completion in most scales. CONCLUSION: The use of once-every-3-weeks cisplatin did not adversely impact QoL as compared to once-a-week cisplatin in combination with radiotherapy in LAHNSCC.

Effect of the Pandemic on Quality-of-Life Data Collection in Prostate Cancer Patients.

PURPOSE: To understand the difficulties that happen during the quality of life (QoL) data collection in a pandemic and provide measures to overcome them. METHODS: We analyzed the recruitment and follow-up data of patients in one of our ongoing study whose aim was to collect the Adverse drug reactions and QoL (at regular intervals) in prostate cancer patients who were on docetaxel. Before the pandemic, we could enroll 31 patients in the study over four months. We analyzed the difficulties experienced by these patients and consultants in collecting QoL data during the pandemic, especially in situations with limited availability of resources and also where the patients are not technologically advanced. RESULTS: Due to the pandemic, we could not recruit a single new patient into the study. Complete QoL assessments were available in only two patients, and the disease progressed in five patients. QoL assessment was not possible in 19 of 31 enrolled patients. More than 44% of the enrolled patients had difficulty commuting to the hospital despite transport services to hospitals. Due to the risk of acquiring COVID19 infection during traveling to the hospital, follow-ups were affected. CONCLUSION: There should be increased support for novel technologies that can successfully capture and transfer patients' QoL data to the treating consultant.

Study of Treatment Outcome in Adults with TFE-Related RCC.

Introduction TFE Translocation renal cell carcinoma (TRCC) represents 1 to 5% of all cases of renal cell carcinoma, with the highest frequency among children and young adults. Management of these tumors is not very well defined in literature. Although in pediatric age group it has favorable prognosis, in adults it has an aggressive nature, with poor outcome. This is a retrospective analysis of treatment outcome in adult patient 18 years or above treated at our hospital between January 2013 and November 2018. Material and Methods Clinical and pathological data of 26 patients from a single institution diagnosed with TRCC between January 2013 and November 2018 were retrospectively reviewed. All cases of TRCC were confirmed with immunohistochemistry or fluorescence in situ hybridization. We analyzed our data of patients treated with surgery only or who progressed after surgery and treated with systemic therapy or who presented with upfront unresectable or metastatic disease treated with systemic therapy with respect to event-free survival (EFS) and overall survival (OS). Results Between January 2013 and November 2018, 26 adult patients who were treated at our center were eligible for this analysis as per our criteria. Out of 26 patients, 25 patients had radical surgery after evaluation and 1 had metastatic disease who was started on systemic therapy. Out 25 patients who were treated with radical surgery, 16 patients progressed and they were started on systemic therapy except for 1 patient who defaulted. Median time to start systemic therapy among patient treated with curative nephrectomy was 13 months. Median EFS and median OS among overall population were 22 and 30 months, respectively. Among 16 patients who were treated with systemic therapy, median EFS to first-line therapy was 8 months and to second-line therapy was 2.5 months. Median OS was 17 months in patients treated with systemic therapy. Conclusion TRCC is rare in adult population but carries significant risk of disease progression even after initial curative treatment with potential response to targeted therapy for short duration.