Publications by authors named "Kumar Prabhash"

256 Publications

Outcomes of osteosarcoma, chondrosarcoma and chordoma treated with image guided-intensity modulated radiation therapy.

Radiother Oncol 2021 Sep 28;164:216-222. Epub 2021 Sep 28.

Department of Nuclear Medicine & Molecular Imaging, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background & Purpose: To evaluate the efficacy and toxicity of dose-escalated image guided-intensity modulated radiation therapy (IG-IMRT) in osteosarcoma (OGS), chondrosarcoma (CS) and chordoma (CH) of head and neck (H&N) and pelvis.

Methods And Materials: In this prospective non-randomized study, 65 patients of H&N or pelvic OGS (24), CS (7) and CH (34) mandating definitive or post-operative radiotherapy from May 2013 to December 2018 were included. Radiotherapy doses in definitive setting were 72.0 Gy for CH and 70.2 Gy for OGS and CS; while in post-operative setting it was 66.6 Gy and 64.8 Gy respectively (at 1.8 Gy per fraction).

Results: Planned doses of radiotherapy could be completed in 61 (93.8%) patients; with grade III or higher acute and late toxicities of 3% and 0% respectively. With a median follow-up of 52 (range 6-92) months, the five-year actuarial local control (LC) rates were 66% in OGS, 38.1% in CS and 75.9% in CH; while cause-specific survival (CSS) rates were 54.7%, 64.3% and 92.2% respectively. There was no statistically significant difference in outcomes for patients receiving definitive and post-operative radiotherapy. Locally controlled disease at first follow-up after radiotherapy was associated with improved CSS and OS in CS (p = 0.014) and CH (p < 0.001). Radiotherapy resulted in significant and sustained improvement in Musculoskeletal tumour society (MSTS) score and reduction in pain score. Salvage re-irradiation was feasible in local progression after radiotherapy, with good outcomes and tolerability.

Conclusion: Dose-escalated IG-IMRT results in good LC & functional improvement with minimal toxicity in OGS, CS and CH.
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http://dx.doi.org/10.1016/j.radonc.2021.09.018DOI Listing
September 2021

Weight loss and its impact on outcome in head and cancer patients during chemo-radiation.

Oral Oncol 2021 Sep 24;122:105522. Epub 2021 Sep 24.

Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre and HBNI, Mumbai 400012, India. Electronic address:

Background: Weight loss during chemotherapy and its impact on the cancer outcomes have been invariably reported in the literature. We also did a post-hoc analysis of a randomized phase III trial to see the same.

Materials And Methods: The database of a recently published randomized study comparing cisplatin-radiation with nimotuzumab cisplatin-radiation was used for this analysis. Week-wise weight loss during the course of treatment was noted. The impact of severe weight loss (grade 2-3) on progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) was studied using the Kaplan Meier method. Binary logistic regression analysis was used to see the effect of various factors.

Results: Out of a total of 536 patients, weight loss was captured in 524. Out of these 524 patients, any degree of weight loss was seen in 293 (55.91%) patients. Grade 1 weight loss was noted in 192 (36.6%) patients, grade 2 in 96 (18.3%) and grade 3 in 5 (1%) patients. The 2-year PFS was 53% and 57.1% in severe and non-severe weight loss groups respectively (p-value = 0.36). The 2-year LRC was 60% in patients with severe weight loss, while it was 63.5% in those with non-severe weight loss (p-value = 0.47). The 2-year OS was 59.3% versus 62.2% in severe and non-severe weight loss cohorts respectively (p-value = 0.21). None of the factors was found to be associated with severe weight loss.

Conclusion: Severe weight loss was uncommon in our patients. Weight loss during treatment was not associated with poor survival outcomes.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105522DOI Listing
September 2021

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

South Asian J Cancer 2021 Apr 4;10(2):92-96. Epub 2021 Sep 4.

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

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. 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). 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. 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.
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http://dx.doi.org/10.1055/s-0041-1731264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460340PMC
April 2021

Demographics, Pattern of Care, and Outcome Analysis of Malignant Melanomas - Experience From a Tertiary Cancer Centre in India.

Front Oncol 2021 8;11:710585. Epub 2021 Sep 8.

Department of Nuclear Medicine, Tata Memorial Hospital, Homibhabha National Institute, Mumbai, India.

Background: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs).

Patients And Methods: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST).

Results: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort.

Conclusions: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.
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http://dx.doi.org/10.3389/fonc.2021.710585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456006PMC
September 2021

An observational study to evaluate factors predicting survival in patients of non-small cell lung cancer with poor performance status in resource-constrained settings.

Ecancermedicalscience 2021 5;15:1274. Epub 2021 Aug 5.

Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai 400012 India.

Background: A significant proportion of non-small cell lung cancer (NSCLC) patients present with poor performance status (PS) at baseline are almost always excluded from the clinical trials leading to availability of only limited data in this subgroup.

Patients And Methods: This was an observational single institutional study. The eligibility criteria for inclusion were a histologic or cytologic diagnosis of advanced NSCLC and Eastern Cooperative Oncology Group PS 3 or 4. All patients coming between June 2015 and December 2018 were evaluated for inclusion in this study.

Results: A total of 245 patients were enrolled in the study. The median age of the patients was 63 years (range 25-89), 142 (58%) were male, 196 (80%) had adenocarcinoma histology and 192 (78.4%) has PS 3 while rest (21.6%) had PS 4. Out of 245 patients, 192 (78.4%) received oral tyrosine kinase inhibitors (TKI) and supportive care, 45 (18.4%) received supportive care alone, while 8 (3.2%) patients received chemotherapy along with supportive care. Median overall survival (OS) was 3 months (95% CI: 1.8-4.2) in patients who received oral TKI versus 1 month (1.0-2.9) in patients who received supportive care alone (log-rank = 0.013). The median OS for epidermal growth factor receptor (EGFR) mutant patients who received oral TKI was 12 months (95% CI: 7.7-16.3), while it was 3 months (95% CI: 1.5-4.5) for patients who were EGFR wild-type and received TKI on compassionate basis (HR = 0.50; 95% CI: 0.32-0.77; = 0.001).

Conclusions: The use of oral TKI on a compassionate basis led to improvement in survival in the overall cohort of the patients; this was principally driven by EGFR-mutated patients.
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http://dx.doi.org/10.3332/ecancer.2021.1274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426023PMC
August 2021

Quality of life in patients with locally advanced head and neck cancer treated with concurrent chemoradiation with cisplatin and nimotuzumab versus cisplatin alone - Additional data from a phase 3 trial.

Oral Oncol 2021 Sep 21;122:105517. Epub 2021 Sep 21.

Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India. Electronic address:

Introduction: The addition of Nimotuzumab to radical chemoradiation (CRT) improved outcomes in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing radical CRT in a phase 3 randomized trial. The current study focuses on the quality of life (QoL) of patients in this trial.

Methods: In this phase III randomized trial, patients with newly diagnosed, nonmetastatic, stage III/IV LAHNSCC of the oral cavity, oropharynx, hypopharynx, or larynx were randomized to receive cisplatin 30 mg/m or cisplatin 30 mg/m with nimotuzumab once a week with curative radiotherapy. The primary end point of the trial was PFS. The aim of the current study was to compare the QoL between the two arms. QoL was assessed using the EORTC QLQ-C30 (v3.0) and HN-35 (v1.0). The linear mixed-effects model was used for longitudinal analysis of QoL.

Results: 536 patients were randomized in this trial (268 in each arm) and 423 patients were included for QoL analysis. There was a significant change in the global health status QoL scores over time (p = 0.0016) with no difference between the two arms (p = 0.396). On longitudinal analysis there was a significant difference in the QoL scores in most of the function & symptom scales over time, but there was no significant difference in these scores between the two arms. QoL scores for most symptom scales worsened during treatment and improved thereafter in both arms.

Conclusion: The addition of nimotuzumab to cisplatin based chemoradiation in LAHNSCC improved PFS, LRC and DFS without negatively impacting QoL.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105517DOI Listing
September 2021

Aspiration pneumonia in head and neck cancer patients undergoing concurrent chemoradiation from India: Findings from a post hoc analysis of a phase 3 study.

Cancer Med 2021 Oct 8;10(19):6725-6735. Epub 2021 Sep 8.

Department of Medical Oncology, Tata Memorial Centre, HBNI, Mumbai, India.

Background: There are limited data from low- to middle-income countries (LMIC) on the incidence, risk factors, treatment outcomes, and antibiotic susceptibility spectrum of aspiration pneumonia (AsP).

Methods: We conducted a post hoc analysis of a randomized control trial in which adult patients with locally advanced head and neck cancers had received 66-70 Gy of radiation combined with cisplatin 30 mg/m weekly for 6-7 weeks or cisplatin at the same dose with nimotuzumab 200 mg once weekly till the completion of radiation. The following data were extracted and analyzed-the incidence of AsP, time to the onset of AsP, risk factors, treatment outcomes of AsP, and its impact on progression-free survival (PFS), locoregional control (LRC) rates, and overall survival (OS).

Results: Out of 536 patients enrolled in the study, 151 (28.3%, 95% confidence interval [CI] 24.5-2.1) patients developed AsP. The median time to develop AsP was 39 days (95% CI 34-44). Only baseline dysphagia (odds ratio = 3.76, 95% CI 1.05-13.51, p = 0.042) was associated with a significant risk of development of AsP. Among the patients in which pathogenic organism was isolated (69 patients), gram-negative species was isolated in 63 patients (89%). Cisplatin at 200 mg/m or more was delivered in 312 (81%) patients in the non-AsP cohort versus 107 (70.9%) patients in AsP cohort (p = 0.014). There was no statistical difference in LRC (hazard ratio [HR] = 1.057; 95% CI 0.771-1.448), PFS (HR = 1.176; 95% CI 0.89-1.553), and OS (HR = 1.233; 95% CI 0.939-1.618) between the two cohorts.

Conclusion: Aspiration pneumonia is a common complication in head and neck malignancies and patients with baseline dysphagia are at high risk. Gram-negative bacteria are the predominant causative agents. The use of broad-spectrum antibiotics results in resolution of symptoms.
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http://dx.doi.org/10.1002/cam4.4210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495270PMC
October 2021

Oral and dental health status in patients undergoing neoadjuvant chemotherapy for locally advanced head and neck cancer.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Nov 31;132(5):539-548. Epub 2021 Jul 31.

Professor and Head of Department, Department of Medical Oncology, Homi Bhabha National Institute, Tata Memorial Hospital, Parel, Mumbai, India.

Objective: A prospective, longitudinal assessment of oral and dental health status was done from baseline until treatment completion in patients scheduled to receive neoadjuvant chemotherapy (NACT) for locally advanced head and neck cancer (LAHNC).

Study Design: One hundred fifty consecutive, treatment-naïve adult patients with biopsy-proven LAHNC scheduled to receive NACT were recruited. One hundred thirty-five patients completed all assessments at 3 designated time points: baseline (T0), midtreatment (T1), and posttreatment (T2). Variables assessed were: Oral Hygiene Index-Simplified (OHI-S) score; decayed, missing, or filled teeth (DMFT) score; mucositis grade; pain score; and grade of trismus.

Results: Median OHI-S scores showed a statistically significant increase (higher the score, poorer the oral hygiene) when the patients were evaluated from baseline to completion of NACT (T1 vs. T2; T0 vs. T2; P < .001), which indicated a decrease in oral health. There was no change in median DMFT score (P = .32), but a significant change was seen in all-grade mucositis over time (P < .001). Median pain scores and trismus grades decreased significantly (P < .001) over time.

Conclusions: There was a decrease in oral health status without any change in dental health seen in patients undergoing NACT. Mucositis was initially noted as an aftermath of chemotherapy, which resolved with time.
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http://dx.doi.org/10.1016/j.oooo.2021.07.018DOI Listing
November 2021

Combined Lu-PSMA-617 PRLT and abiraterone acetate versus Lu-PSMA-617 PRLT monotherapy in metastatic castration-resistant prostate cancer: An observational study comparing the response and durability.

Prostate 2021 Nov 1;81(15):1225-1234. Epub 2021 Sep 1.

Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, India.

Objective: The aim of present study was to determine and compare the overall response rates, progression-free survival (PFS), overall survival (OS), and clinical toxicity of the combination of 177Lu-PSMA-617 radioligand therapy (PRLT) and abiraterone acetate (AA) versus 177Lu-PSMA-617 PRLT as monotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients.

Materials And Methods: The mCRPC patients who received at least one cycle of Lu-PSMA-617 PRLT with or without AA therapy, were included and analyzed in the present study. The patients were divided into two major groups. Group 1 received only Lu-PSMA PRLT and Group 2 received combined Lu-PSMA PRLT + AA therapy. Therapeutic dose of Lu-PSMA-617 PRLT was 4.4-5.55 GBq per patient per cycle administered at intervals of 10-12 weeks in both groups. The Group 2 patients additionally received a dose of 1000 mg of AA once daily and 5 mg of prednisone twice daily. Treatment response in two groups was evaluated under four broad categories (a) symptomatic, (b) biochemical (serum prostate-specific antigen level), (c) objective molecular imaging ( Ga-PSMA-11 and F-FDG PET/CT), and (d) objective anatomical imaging (computed tomography). For assessing treatment response, patients in two groups were categorized into responders (complete response [CR], partial response [PR], and stable disease [SD]) and nonresponders (progressive disease [PD]). The Kaplan-Meier product-limit method was used to calculate PFS and OS following first Lu-PSMA PRLT in the two groups. Univariate analysis was used to compare the patients' characteristics in two groups using a χ or Fisher exact test. The Kaplan-Meier curves of PFS and OS between two groups were compared by using the log-rank test (p < 0.05 significant).

Results: A total of 58 mCRPC patients (Group 1, 38 patients and Group 2, 20 patients) were included in this study analysis. The clinical and demographic characteristics of these patients (age, Gleason score, FDG avid disease, metastatic disease burden, and average number of Lu-PSMA PRLT cycles) in two groups were compared and found to be similar (p > 0.05). Post-treatment, symptomatic, biochemical, molecular, and anatomic imaging responders were found in 22 patients (58%) and 17 patients (85%), 22 patients (58%) and 16 patients (80%), 19 patients (54%) and 14 patients (78%), and 19 patients (54%) and 14 patients (78%) in Group 1 and Group 2, respectively. The median PFS of 7 months and median OS of 8 months were documented in Group 1, whereas median PFS was not reached and median OS of 16 months registered in Group 2. Transient hematological toxicity of Grades 1 and 2 was found in total seven patients (five patients in Group 1 and two patients in Group 2). On comparison of the treatment outcome between two groups, significant p value was found for symptomatic responders (58% in Group 1 vs. 85% in Group 2), median PFS (7 months in Group 1 vs. not reached in Group 2), and median OS (8 months in Group 1 vs. 16 months in Group 2), with better outcome in Group 2 patients for these variables.

Conclusion: In the present study, the combination of Lu-PSMA-617 PRLT and AA therapy showed significant improvement in mCRPC patients' symptomatic response, PFS, and OS as compared to Lu-PSMA-617 PRLT monotherapy.
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http://dx.doi.org/10.1002/pros.24219DOI Listing
November 2021

Neuroendocrine Neoplasms of the Larynx: A Clinicopathologic Analysis of 27 Neuroendocrine Tumors and Neuroendocrine Carcinomas.

Head Neck Pathol 2021 Aug 16. Epub 2021 Aug 16.

Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.

Laryngeal neuroendocrine neoplasms (NENs) are rare and heterogeneous, encompassing well-differentiated neuroendocrine tumors (NETs; grade 1, 2, and 3), neuroendocrine carcinomas (NECs, small cell and large cell types), and mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN). We aimed to study the clinicopathologic spectrum of these neoplasms. A retrospective review of all primary laryngeal NENs diagnosed from 2005 to 2017 was undertaken. Mitotic index was divided into < 2, ≥ 2-10, and > 10 mitoses/2 mm, with a Ki-67 labelling index of < 2%, ≥ 2-20%, and > 20% for the NET grade 1, 2 and 3 categories, respectively. A total of 27 patients were included. The median age at presentation was 60 years; the male-to-female ratio was 8:1. Supraglottis (n = 22) was the most frequently affected subsite. There were 9 NETs grade 2 (G2), and 18 NECs cases. There were no NET grade 1 or 3 cases in our cohort. Among the NETs G2, the morphology was epithelioid (2), plasmacytoid (3), clear (2), oncocytic (1), and rhabdoid (1). Unique 'glomeruloid structures' (n = 5), calcification (n = 3), lymphoid aggregates (n = 5), intranuclear inclusions (n = 2), hyaline globules (n = 3), and Leisegang rings (n = 2) were identified. NECs comprised 16 small cell neuroendocrine carcinoma and 2 large cell neuroendocrine carcinoma. On immunohistochemistry, tumor cells expressed AE1/AE3 (86%), synaptophysin (100%), chromogranin (100%), INSM1 (100%), calcitonin (33.3%). In the NEC group, p53 aberrant expression (87.5%), Retinoblastoma (Rb) loss (88.2%), and diffuse p16 immunoreactivity (66.7%) were additionally observed. Lymph-node metastasis was detected in 62.5% and 85.7%, while distant metastasis in 55.6% and 76.9%, respectively in NET G2 and NEC. Laryngeal NENs are aggressive neoplasms with a high rate of nodal and distant metastasis. Awareness of the wide pathologic spectrum of laryngeal NENs and appropriate use of IHC is needed to render an accurate diagnosis. Ki67 assessment is strongly recommended for laryngeal NEN prognostication.
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http://dx.doi.org/10.1007/s12105-021-01367-9DOI Listing
August 2021

CD26 expression on donor harvest as a risk predictive biomarker for developing Graft-versus-Host Disease post-Allogeneic Hematopoietic Stem Cell Transplantation: A tenyear followup study.

Cancer Biomark 2021 Jul 15. Epub 2021 Jul 15.

Tumor Immunology and Immunotherapy Group, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India.

Background: Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft versus host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long term transplant outcomes.

Objective: Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes.

Methods: This study includes donor harvests collected from twenty-three allogeneic donors during period 2008-2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in donor harvest were analyzed using flow cytometry. Percent expression and infused dose of CD26+ and CD34+ cells were evaluated for association with various clinical outcomes.

Results: Total 23 healthy donors 28 years (13 males), and transplant recipients with median age 24 years (17 males) formed the study cohort. The diagnosis included malignant (n= 13) and non-malignant (n= 10) disorders. Median CD34brCD45lo HSC expression was 057% (IQR 024-103) while median CD26 expression was 1964% (IQR 896-3356) of all nucleated cells. CD26 expression was associated with donor age (P= 0.37). CD26 percent expression correlated with WBC engraftment (P= 0.015) and with acute GVHD (P= 0.023) whereas infused CD26 cell dose correlated with WBC engraftment (P= 0.004) and risk of CMV reactivation (P= 0.020). There was no statistically significant correlation of either CD26 expression or cell dose with chronic GVHD, EFS or OS.
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http://dx.doi.org/10.3233/CBM-210137DOI Listing
July 2021

Advances in pharmacotherapy for head and neck cancer.

Expert Opin Pharmacother 2021 Oct 30;22(15):2007-2018. Epub 2021 Jun 30.

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and is a leading cause for cancer-related mortality. This review attempts to give a comprehensive summary of the recent developments in pharmacotherapeutic options for locally advanced/metastatic HNSCC. In this review, the authors conducted a systematic literature search for published articles on HNSCC in the PubMed database using the keywords 'head and neck squamous cell carcinoma or HNSCC,' 'targeted therapy,' 'immunotherapy.' The search was restricted to meta-analyses, clinical trials, practice guidelines, and abstract presentations at international meetings. The final search encompassed articles published from 2010 to 2021. Articles published in languages other than English were excluded. Immune checkpoint inhibition has been the most significant advance in the treatment of R/M HNSCC. Oral metronomic therapy has emerged as an important therapeutic option for low to middle-income countries. H-RAS inhibition is one of the most promising areas of research.
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http://dx.doi.org/10.1080/14656566.2021.1948011DOI Listing
October 2021

ADME gene polymorphisms do not influence the pharmacokinetics of docetaxel: Results from a population pharmacokinetic study in Indian cancer patients.

Cancer Med 2021 07 22;10(14):4948-4956. Epub 2021 Jun 22.

Department of Clinical Pharmacology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, India.

Background: Pharmacokinetics (PK) of docetaxel is characterized by high inter-individual variability (IIV). While covariate models that explain the PK variability of docetaxel exist, not much is known about the effects of genetic variations on docetaxel disposition.

Methods: Fifty patients with head and neck or prostate cancer were enrolled of whom two patients withdrew consent before the start of the study. Docetaxel was administered at either 50 or 75 mg/m as intravenous infusion over 1 h. One pharmacogenetic sample and a series of PK samples, either intensive (N = 5; 13 samples each) or sparse (N = 43; 6 samples each), were collected from each patient. Docetaxel levels were estimated using a validated HPLC method. Polymorphic loci on the Absorption, Distribution, Metabolism, and Elimination (ADME) genes were identified using the PharmacoScan array platform. Population pharmacokinetic analysis was carried out using NONMEM v7.2.

Results: Docetaxel PK was well characterized by a three-compartment model. Clearance (Cl) was found to be 18 L/h with an IIV of 45.3%. None of the genetic variants showed significant covariate effect on the Cl of docetaxel. Patients with abnormal alanine aminotransferase (ALT) were found to have 25% lower Cl as compared to patients with normal ALT values. However, the covariate effect could not be established in the final model possibly due to lack of adequate number of patients with abnormal ALT.

Conclusion: Genetic polymorphisms in the ADME gene do not explain the IIV in PK of docetaxel. However, patients with abnormal liver function might require dose reduction.

Clinical Trial Registration: Not applicable since participants in this study received treatment that was standard of care.
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http://dx.doi.org/10.1002/cam4.4026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290241PMC
July 2021

Chemoradiation in Unresectable Oral Cavity Cancer: A Myth or Reality!

South Asian J Cancer 2020 Oct 12;9(4):195-198. Epub 2021 Jun 12.

Department of Medical Oncology, HBNI, Tata Memorial Hospital, Mumbai, Maharashtra, India.

 Earlier studies have shown that chemoradiation (CTRT) has benefits in the head-and-neck cancer, but how far it is true for oral cavity subset that has not been exactly explored. Keeping the null hypothesis as CTRT has no benefit in oral cavity cancer, we studied the outcome of patients undergoing chemoradiation in unresectable oral cavity cancers. The aim of this study is to study whether overall survival (OS) increases with chemoradiation in unresectable oral cavity cancers.  Between December 2014 and February 2017, 23 patients aged 18 years and above were planned chemoradiation for unresectable oral cavity cancer and were included for this analysis.  The median age of patients was 43 years and all patients were addicted to tobacco. In total, 12 of 23 (52%) completed CTRT. One patient (1/23) was alive at the time of final analysis with median OS of 5.83 (2.73-9.60) months. The median progression free survival and OS in patients who completed chemoradiation were 6.42 months (95% confidence interval [CI]: 3.67-10.53) and 8.9 months (95% CI: 4.4-23.07), respectively.  CTRT has a limited role in unresectable oral cancers.
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http://dx.doi.org/10.1055/s-0041-1728225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197656PMC
October 2020

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

Ann Diagn Pathol 2021 Aug 26;53:151763. Epub 2021 May 26.

Department of Thoracic Surgery, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

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.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151763DOI Listing
August 2021

Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III NSCLC: Results of KINDLE, a Multicountry Observational Study.

J Thorac Oncol 2021 10 26;16(10):1733-1744. Epub 2021 May 26.

Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.

Introduction: Stage III NSCLC is a heterogeneous disease requiring a multimodal management approach. We conducted a real-world, global study to characterize patients, treatment patterns, and their associated clinical outcomes for stage III NSCLC.

Methods: KINDLE was a retrospective study in patients with stage III NSCLC (American Joint Committee on Cancer, seventh edition) diagnosed between January 2013 and December 2017, with at least 9 months of documented follow-up since index diagnosis. In addition to descriptive statistics, Kaplan-Meier methodology evaluated survival estimates; two-sided 95% confidence interval was computed. Cox proportional hazards model was used for univariate and multivariate analyses.

Results: A total of 3151 patients from more than 100 centers across 19 countries from Asia, Middle East, Africa, and Latin America were enrolled. Median age was 63.0 years (range: 21.0-92.0); 76.5% were males, 69.2% had a smoking history, 53.7% had adenocarcinoma, and 21.4% underwent curative resection. Of greater than 25 treatment regimens, concurrent chemoradiotherapy was the most common (29.4%). The overall median progression-free survival (95% confidence interval) and median overall survival (mOS) were 12.5 months (12.06-13.14) and 34.9 months (32.00-38.01), respectively. Significant associations (p < 0.05) were observed for median progression-free survival and mOS with respect to sex, region, smoking status, stage, histology, and Eastern Cooperative Oncology Group status. In univariate and multivariate analyses, younger age, stage IIIA, better Eastern Cooperative Oncology Group status, concurrent chemoradiotherapy, and surgery as initial therapy predicted better mOS.

Conclusions: KINDLE reveals the diversity in treatment practices and outcomes in stage III NSCLC in a real-world setting in the preimmuno-oncology era. There is a high unmet medical need, necessitating novel approaches to optimize outcomes.
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http://dx.doi.org/10.1016/j.jtho.2021.05.003DOI Listing
October 2021

Post hoc analysis of a randomized controlled trial comparing concurrent chemoradiation with cisplatin versus nimotuzumab-cisplatin, focusing on acute oral mucositis.

J Egypt Natl Canc Inst 2021 May 22;33(1):12. Epub 2021 May 22.

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, 400012, India.

Background: Acute oral mucositis has been infrequently studied in the patients with head and neck squamous cell carcinoma (HNSCC) receiving once-weekly cisplatin-based chemoradiotherapy (CRT). Hence, this analysis was conducted to explore the various aspects of the same.

Results: The overall incidence of mucositis was 96.9% (n = 508) and of grade 3-5 mucositis was 61.3% (n = 321). The overall incidence of oral mucositis was similar in both the arms (CCRT and NCRT) (p value = 0.58) while grade 3-5 mucositis was more common in the NCRT arm (p value = 0.01). Out of all factors listed, the presence of nimotuzumab was the only significant risk factor for the development of grade 3 or more oral mucositis (p value = 0.01); (OR = 1.64, 95%CI 1.15-2.32). Delays in the treatment delivery were similar in both the arms.

Conclusion: Acute oral mucositis is a common occurrence in locally advanced-HNSCC patients receiving chemoradiotherapy. Nimotuzumab is a significant factor for development of grade 3 and above oral mucositis.
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http://dx.doi.org/10.1186/s43046-021-00069-1DOI Listing
May 2021

Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs.

Transl Oncol 2021 Aug 13;14(8):101111. Epub 2021 May 13.

Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education In Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India 410210; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, India 400094. Electronic address:

The recently conducted ADAURA trial concludes daily dosing of adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), improves disease-free survival with stage IB/II/IIIA EGFR -mutated non-small cell lung cancer patients in comparison to placebo. We have developed a preclinical orthotopic mouse model, using luciferase tagged lung adenocarcinoma cells harboring EGFR TKI sensitive exon 19 deletion to model and extend trial implications comparing a weekly vs daily dosing outcome of osimertinib to a first-generation TKI- erlotinib. We find that 100% of mice in both the groups receiving osimertinib daily or weekly before injection of cells show a complete absence of homing of cells in mice's lungs from day three until day 18 post-injection of cells. On the other hand, 25% and 75% of mice receiving erlotinib daily and weekly before injecting cells show homing of cells to the lungs. The tumors observed in the lungs, when dissected at day 30, confirmed the colonization of the injected cells homing to the organ. Thus, our study establishes the efficacy of pretreatment with osimertinib in reducing tumor cells' homing to mouse lungs in an in vivo mouse model.
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http://dx.doi.org/10.1016/j.tranon.2021.101111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236545PMC
August 2021

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country.

Pediatr Blood Cancer 2021 Sep 15;68(9):e29081. Epub 2021 May 15.

Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.

Background: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration.

Methods: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS).

Results: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114 (48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow-up of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths.

Conclusions: The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.
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http://dx.doi.org/10.1002/pbc.29081DOI Listing
September 2021

Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations.

Oncotarget 2021 Mar 16;12(6):578-588. Epub 2021 Mar 16.

Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India.

Introduction: Unlike lung adenocarcinoma patients, there is no FDA-approved targeted-therapy likely to benefit lung squamous cell carcinoma patients.

Materials And Methods: We performed survival analyses of lung squamous cell carcinoma patients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors.

Results: We report a mean of 11.6 mutations/Mb with a characteristic smoking signature along with mutations in and among lung squamous cell carcinoma patients of Indian descent. In addition, therapeutically relevant mutations occur in 5.8% patients, significantly higher than as reported among Caucasians. In overall, our data suggests 13.5% lung squamous patients harboring druggable mutations have lower median overall survival, and 19% patients with a mutation in at least one gene, known to be associated with cancer, result in significantly shorter median overall survival compared to those without mutations.

Conclusions: We present the first comprehensive landscape of genetic alterations underlying Indian lung squamous cell carcinoma patients and identify and as potentially important therapeutic and prognostic target.
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http://dx.doi.org/10.18632/oncotarget.27905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984830PMC
March 2021

Immune checkpoint inhibitors in patients with solid tumors and poor performance status: A prospective data from the real-world settings.

Medicine (Baltimore) 2021 Apr;100(13):e25115

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Abstract: Immune checkpoint inhibitors (ICIs) are rapidly being incorporated as treatment option either alone or in combination with chemotherapy in most of the solid tumors. Since there is very limited data of ICI in patients with poor performance status (PS) from the real world settings, we performed a retrospective audit of patients who received ICI and report the analysis based on ECOG PS of these patients.This study is a retrospective audit of a prospectively collected database of patients receiving ICIs for advanced solid tumors in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. All statistical calculations were performed using SPSS statistical software for windows version 20.0.A total of 155 patients who received ICIs during the specified period were evaluated for this study. Baseline ECOG PS 0-1 (n = 103, 66.4%) patients was associated with median OS 9.1 (95% CI [confidence interval], 4.4-NR) months when compared to ECOG 2-4 (n = 52, 33.5%) which had a median OS of 2.9 (95% CI; 1.8-5.5) months (HR, 1.7, 95% CI, 1.1-2.7, log rank P = .017). The disease control rate for the poor PS group was 34.6%. However, 27.3% patients (95% CI: 20.3-34.3) were still alive at 1 year. Median OS in patients with PS 2 was 3.7 months (95% CI: 0-11.6) as compared to 1.8 months (95% CI: 0.2-3.4) for those with PS 3-4 (HR-2.0; 95% CI: 1.0-3.9, P = .041). The tolerance to ICIs was good with no grade 3/4 toxicities in 44 (84.6%) patients.Immune checkpoint inhibitors are a safe and effective therapeutic option even in solid tumor patients with poor performance status.
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http://dx.doi.org/10.1097/MD.0000000000025115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021372PMC
April 2021

Correlation of transcriptionally active human papillomavirus status with the clinical and molecular profiles of head and neck squamous cell carcinomas.

Head Neck 2021 07 10;43(7):2032-2044. Epub 2021 Mar 10.

Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.

Background: To examine the molecular profiles of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas (HNSCCs), expression of epidermal growth factor receptor (EGFR), phospho-EGFR dimers, hypoxia markers, and cancer stem cell markers were evaluated.

Methods: HPV-status was confirmed using RNA-ISH. Immunohistochemical data of biomarker expression levels were analyzed using the Mann-Whitney U test. The clinical outcomes and biomarker expression in the HPV-positive (n = 25), matched HPV-negative (n = 49), and p16-positive/HPV-negative (n = 20) subgroups were comparatively analyzed.

Results: HPV was detected in 25 (5.8%) cases and was significantly associated with favorable outcomes. HPV-positive tumors exhibited lower membrane expression of EGFR, pEGFRY1068, pEGFRY1173, CD44, CD44v6, and CD98hc than HPV-negative and p16-positive tumors. The expression of HIF1α, CA9, ALDH1A1, and SOX2 was not significantly associated with HPV-status. The clinical outcomes and biomarker expression levels were similar between the HPV-negative and p16-positive HNSCC.

Conclusion: HPV-positive HNSCC exhibited distinct molecular profile compared to HPV-negative and p16-positive HNSCC. The clinical and molecular profiles were similar between p16-positive and HPV-negative subgroups.
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http://dx.doi.org/10.1002/hed.26676DOI Listing
July 2021

Standard maintenance therapy versus local consolidative radiation therapy and standard maintenance therapy in 1-5 sites of oligometastatic non-small cell lung cancer: a study protocol of phase III randomised controlled trial.

BMJ Open 2021 03 16;11(3):e043628. Epub 2021 Mar 16.

Clinical Research Secretariat, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

Introduction: Two-phase II randomised studies have shown a significant benefit of local consolidation therapy in oligometastatic non-small cell lung cancer (NSCLC). This phase III randomised controlled trial (RCT) will evaluate the efficacy of local consolidation radiation therapy (RT) in oligometastases (OM) NSCLC after completion of initial systemic therapy.

Methods And Analysis: This is a single-centre phase III RCT of OM NSCLC patients. One hundred and ninety patients will undergo 1:1 randomisation to either standard maintenance therapy (control arm) or local consolidation RT and standard maintenance therapy (experimental arm). Patients will be stratified into the number of OM sites (1-2 vs 3-5), nodal metastases (N0-N1 vs N2-N3) and presence or absence of brain metastases. Stereotactic body radiation therapy to all the oligometastatic sites and definitive RT to primary disease will be given in the experimental arm. The primary endpoint is overall survival and secondary endpoints include progression-free survival, local control of OM sites, new distant metastases free survival, objective response rate, toxicity and quality of life. Translation endpoint include circulating tumour cells and radiomics using texture analysis.

Ethics And Dissemination: All patients will be provided with a written informed consent form which needs to be signed before randomisation. The study is approved by the institutional ethics committee-II (project number 3445) and registered with Clinical Trials Registry-India, dated 21 April 2020.

Trial Registration Number: CTRI/2020/04/024761; Pre-Results.
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http://dx.doi.org/10.1136/bmjopen-2020-043628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970230PMC
March 2021

Distress Screening in Head and Neck Cancer Patients Planned for Cancer-Directed Radiotherapy.

Laryngoscope 2021 09 15;131(9):2023-2029. Epub 2021 Mar 15.

Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.

Objective/hypothesis: To estimate the prevalence of baseline clinically significant distress (distress score ≥ 4) in head and neck cancer patients planned and treated with radical intent radiotherapy using the National Comprehensive Cancer Network Distress Thermometer (DT) and assess factors predictive of distress.

Study Design: Cross-sectional study.

Methods: This was a cross-sectional study evaluating distress in 600 head and neck cancer patients undergoing radiation therapy. The DT was used to screen patients for distress at baseline before radiotherapy.

Results: The median distress score of the entire cohort was 4 interquartile range (IQR) (IQR: 3-5), and 340 patients (56.7%) had clinically significant distress. On univariate analysis, the causal factors predictive of distress were low socioeconomic status (P = .04), presence of proliferative growth at presentation (P = .008), site of the tumor (oral cavity, P = .02), comorbidity (P = .04), and presence of Ryle's tube or tracheostomy tube at baseline (P = .01). Low socioeconomic status was significant (P = .04) on multivariate analysis for high levels of distress.

Conclusions: Among head and neck cancer patients, 56% of patients had clinically significant baseline distress, and patients with low socioeconomic status had high distress. There is a need for interventions to mitigate distress.

Level Of Evidence: 4 Laryngoscope, 131:2023-2029, 2021.
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http://dx.doi.org/10.1002/lary.29491DOI Listing
September 2021

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

Head Neck 2021 07 9;43(7):2045-2057. Epub 2021 Mar 9.

Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Background: To assess the efficacy of intensity-modulated radiation therapy (IMRT) for tumors of the nasal cavity and paranasal sinus (PNS) region.

Materials And Methods: Two hundred fourteen patients with tumors of the nasal cavity and PNS region treated with curative intent IMRT between 2007 and 2019 were included in this retrospective analysis.

Results: Fifty-one (24.1%) received definitive RT/CTRT and 163 (75.9%) received adjuvant RT. Most common histology was squamous cell carcinoma (26.1%) followed by adenoid cystic carcinoma (21.5%). The median follow-up was 43.5 months. The 5-year local control (LC), event-free survival (EFS), and overall survival (OS) for the entire cohort was 66.9%, 59%, and 73.9%, respectively. On univariate analysis treatment with nonsurgical modality, T classification and undifferentiated/poorly differentiated histology were associated with inferior 5-year LC, EFS, and OS. Four patients had late Grade 3/Grade 4 ocular toxicity.

Conclusions: IMRT should be the standard of care for tumors of PNS region across all histologies and treatment setting.
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http://dx.doi.org/10.1002/hed.26669DOI Listing
July 2021

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

Ther Adv Drug Saf 2021 11;12:2042098621991280. Epub 2021 Feb 11.

Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India Homi Bhabha National Institute, Mumbai, India.

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: 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.
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http://dx.doi.org/10.1177/2042098621991280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882752PMC
February 2021

Shared Decision-Making and Medicolegal Aspects: Delivering High-Quality Cancer Care in India.

Indian J Palliat Care 2020 Oct-Dec;26(4):405-410. Epub 2020 Nov 19.

Department of Oncology, Merck Specialities Pvt. Ltd., India, Merck KGaA, Darmstadt, Germany.

It is often difficult for people with cancer to make decisions for their care. The aim of this review is to understand the importance of shared decisionmaking (SDM) in Indian clinical scenario and identify the gaps when compared to practices in the Western world. A systematic search (2000-2019) was executed in Medline and Google Scholar using predefined keywords. Of the approximate 400 articles retrieved, 43 articles (Indian: 5; Western: 38) were selected for literature review. Literature review revealed the paucity of information on SDM in India compared to the Western world data. This may contribute to patientreported physical or psychological harms, life disruptions, or unnecessary financial costs. Western world data demonstrate the involvement and sharing of information by both patient and physician, collective efforts of the two to build consensus for preferred treatment. In India, involvement of patients in the planning for treatment is largely limited to tertiary care centers, academic institutes, or only when the cost of therapy is high. In addition, cultural beliefs and prejudices impact the extent of participation and engagement of a patient in disease management. Communication failures have been found to strongly correlate with the medicolegal malpractice litigations. Research is needed to explore ways to how to incorporate SDM into routine oncology practice. India has a high unmet need towards SDM in diagnosis and treatment of cancer. Physicians need to involve patients or their immediate family members in decision making, to make it a patient-centric approach as well. SDM enforces to avoid uninformed decisionmaking or a lack of trust in the treating physician's knowledge and skills. Physician and patient education, development of tools and guiding policies, widespread implementation, and periodic assessments may advance the practice of SDM.
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http://dx.doi.org/10.4103/IJPC.IJPC_237_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888410PMC
November 2020

Effect of Early Palliative Care on Quality of Life of Advanced Head and Neck Cancer Patients: A Phase III Trial.

J Natl Cancer Inst 2021 Sep;113(9):1228-1237

Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background: Early palliative care (EPC) is an important aspect of cancer management but, to our knowledge, has never been evaluated in patients with head and neck cancer. Hence, we performed this study to determine whether the addition of EPC to standard therapy leads to an improvement in the quality of life (QOL), decrease in symptom burden, and improvement in overall survival.

Methods: Adult patients with squamous cell carcinoma of the head and neck region planned for palliative systemic therapy were allocated 1:1 to either standard systemic therapy without or with comprehensive EPC service referral. Patients were administered the revised Edmonton Symptom Assessment Scale and the Functional Assessment of Cancer Therapy for head and neck cancer (FACT-H&N) questionnaire at baseline and every 1 month thereafter for 3 months. The primary endpoint was a change in the QOL measured at 3 months after random assignment. All statistical tests were 2-sided.

Results: Ninety patients were randomly assigned to each arm. There was no statistical difference in the change in the FACT-H&N total score (P = .94), FACT-H&N Trial Outcome Index (P = .95), FACT-general total (P = .84), and Edmonton Symptom Assessment Scale scores at 3 months between the 2 arms. The median overall survival was similar between the 2 arms (hazard ratio for death = 1.01, 95% confidence interval = 0.74 to 1.35). There were 5 in-hospital deaths in both arms (5.6% for both, P = .99).

Conclusions: In this phase III study, the integration of EPC in head and neck cancer patients did not lead to an improvement in the QOL or survival.
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http://dx.doi.org/10.1093/jnci/djab020DOI Listing
September 2021

A real-world data of Immune checkpoint inhibitors in solid tumors from India.

Cancer Med 2021 03 16;10(5):1525-1534. Epub 2021 Feb 16.

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.

Background: Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors.

Methods: This was a single center retrospective analysis of prospective data base of patients with non-melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints.

Results: Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non-small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non-melanoma solid malignancies was 5.37 months (95% CI, 3.73-9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73-3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%.

Conclusion: Real-world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non-melanoma solid tumors.
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http://dx.doi.org/10.1002/cam4.3617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940210PMC
March 2021
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