Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

BACKGROUND OBJECTIVES: The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. METHODS: A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. RESULTS: Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. INTERPRETATION CONCLUSIONS: Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

Clinical outcomes of ROS1-positive non-small cell lung cancer with limited access to ROS1-tyrosine kinase inhibitors (TKIs): experience from an Indian tertiary referral centre.

Introduction: ROS1 as a driver mutation is observed in approximately 1%-2% of all non-small cell lung cancer (NSCLC). Given its rarity, we share our experience regarding ROS1-positive NSCLC including the access to ROS1 tyrosine kinase inhibitors (TKIs) in a low-middle income country like India. Methods: It is a retrospective analysis of ROS1-positive NSCLC patients registered between January 2015 to December 2021 for demographics, treatment patterns and outcomes i.e., overall survival (OS) and progression free survival (PFS). Results: Baseline characteristics were available for 70 patients of 78 patients positive for ROS1 by fluorescent in situ hybridisation. Median age at presentation was 52 years, 39 (55.7%) were males, most (51, 72.86%) were non-smokers and ten patients (14.3%) had poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) i.e., PS >2 at presentation. A total of 67 patients receiving cancer directed therapy were analysed for survival. The first line (1L) therapies included - ROS1 TKIs in 38, chemotherapy in 20, epidermal growth factor receptor TKI in eight and chemotherapy-bevacizumab in one only. ROS1 TKI was provided to 20 patients as part of an assistance programme. The median OS for patients who received ROS1 TKI was not attained (95% CI 37.85-NA), while it was 8.11 (95% CI 6.31-NA) months for those who did not (HR-0.1673). The median PFS for the 1L ROS1 TKI compared to the no-TKI group was 27.07 (95% CI 24.28-NA) months versus 5.78 (95% CI 3.42-12) months (HR: 0.2047). Poor ECOG PS at presentation was the only independent prognosticator for survival. Conclusion: Using ROS1 TKI improves clinical outcomes in all-comers though statistically not significant. To further improve outcomes, future trials should pay special attention to patients with poor PS and find a way to increase the current limited access to TKI.

Feasibility of Delivering High-Dose Methotrexate in Adolescent and Adult All Patients: A Retrospective Study.

Introduction HD-MTX is a key drug in the treatment protocols for ALL. The regimen needs to be administered with appropriate supportive measures and serum methotrexate level monitoring. A limited testing strategy is relevant in resource constraint settings since it allows a shorter duration of hospitalization. We report our experience with this strategy and its impact on the patient safety outcomes. Methods This is a retrospective study of all patients ≥ 15 years of age with newly diagnosed ALL or Lymphoblastic lymphoma (LBL) who were administered HDMTX (part of BFM-90 ALL protocol) at our institute between March 2013 to November 2013.The medical records were reviewed for clinical characteristics, disease-related details, HDMTX dose and cycles administered, leucovorin rescue and toxicities. Results A total of 423 cycles of HD-MTX were administered to 106 patients during the study period. The median duration for completion of all 4 cycles of HDMTX was 53 (IQR 49-60) days. The grade 3 or higher toxicities were anemia in 9.6%, neutropenia 19.4%, febrile neutropenia 5.7%, thrombocytopenia 4.4% and mucositis in 0.7%. There was statistically significant correlation between the levels at 42 h (≤ 1 mmol/L vs > 1 mmol/L) and toxicity- anemia, FN and mucositis observed more in the late clearance group. With limited sampling strategy whereby if the 42- hour level MTX level are < 1 mmol/L, 57% of patients could be discharged early. Conclusion HD-MTX can be safely administered to adolescent and adult ALL patients. A limited methotrexate level monitoring is a safe strategy that can optimize the resources better.

Treatment pattern and outcomes in de novo T790M-mutated non-small cell lung cancer.

Introduction: Limited data exists for non-small cell lung cancer (NSCLC) patients harbouring de novo T790M mutation. Methods: NSCLC patients, with de novo T790M, who registered at our institute between 01/03/2015 and 31/12/2019, were considered for retrospective analysis of treatment pattern and clinical outcomes, i.e., progression-free survival (PFS) and overall survival (OS). Results: Of 1,542 epidermal growth factor receptor (EGFR)-mutated patients, 40 (2.59%) had de novo T790M. Most were male (27, 67.5%) and smokers (23, 57.5%). The commonest site of metastasis was the lungs (31, 77.5%), while 7 (17.5%) had central nervous system (CNS) involvement. Additional EGFR gene mutations and anaplastic lymphoma kinase (ALK) positivity were observed in 20 (50.0%) and 4 (10.0%) cases, respectively. The first-line systemic therapy and the number of patients receiving it were as follows: osimertinib by 14 (35.0%), first-generation EGFR tyrosine kinase inhibitors (TKIs) by 10 (25.0%), gefitinib + chemotherapy by 3 (7.5%), chemotherapy by 7 (17.5%) and gefitinib + bevacizumab by 2 (5%). One patient defaulted before starting any treatment. Hence, 39 were considered for survival analysis. The median PFS and OS for the entire cohort were 10.4 (95% CI = 7.6-19.7) months and 24.9 (95% CI = 15.7-NA) months, respectively. The median PFS for patients on osimertinib was 19.8 (95% CI = 11.6-28.0) months versus 8.8 (95% CI = 6.6-10.9) months for those on other systemic therapy. No CNS involvement, use of osimertinib or first-generation EGFR TKI plus chemotherapy or ALK inhibitor in ALK-positive cases prognosticated better PFS. When compared to other systemic therapies, osimertinib improved PFS in patients with or without additional EGFR mutations, although it was statistically significant for the former group only (p = 0.002). Conclusion: The incidence of de novo T790M is low. Osimertinib in frontline therapy provides promising outcomes.

Small cell carcinoma of the oesophagus: experience of an Indian Tertiary Cancer Centre.

Introduction: Small cell carcinoma of the oesophagus (SCCE) is a rare and aggressive tumour with no established standard treatment. Methods: This is a retrospective study of adult patients with histologically proven SCCE registered between February 2011 and March 2020 at Tata Memorial Hospital in Mumbai. Results: There were 56 patients, with 29 (51.8%) having limited-stage disease (LD) and 27 (48.2%) having extensive-stage disease (ED). The median age was 58 (interquartile range = 51-65) years; 57.1% were men; and 40% were smokers. Among LD-SCCE patients, 23 underwent local therapy, i.e., radiation (19, 65.5%) and surgery (4, 13.8%), and 27 received chemotherapy in neoadjuvant (23, 79.3%), concurrent (18, 62.1%) and adjuvant (4, 13.8%) settings. Totally, 19 ED-SCCE patients (70.4%) received chemotherapy. Prophylactic cranial irradiation (PCI) was delivered to 11 (37.9%) and 7 (25.9%) patients with LD-SCCE and ED-SCCE, respectively. Significant grade 3 or more chemotoxicities in patients with LD-SCCE and ED-SCCE included febrile neutropenia in 33.3% and 23.5%, anaemia in 9.5% and 17.6%, and dyselectrolytemia in 14.3% and 11.8%, respectively. The median overall survival (OS) in LD-SCCE and ED-SCCE was 22.9 (95% CI = 1.8-44.1) months and 11.8 (95% CI = 7.3-16.4) months, respectively. Age <60 years (p = 0.004) and tumour epicentre in the lower third oesophagus (p = 0.002) were independent good prognostic factors for OS in LD-SCCE and ED-SCCE patients, respectively. The incidence of brain metastasis was low, at both presentation (1/27, 3.7%) and relapse (5/56, 8.9%). Conclusion: Although the survival of LD-SCCE is better than ED-SCCE, it is still under 2 years. Brain metastases are uncommon and the role of PCI is uncertain.

Outcomes of Ewing sarcoma in adults over 40 years of age from a low-middle income country.

Introduction: The data on outcomes and toxicity in adult Ewing sarcoma (ES) patients, particularly those aged ≥40 years, is exceedingly scarce around the world, particularly in low- and middle-income countries (LMICs) and mandates research. Methods: The study involved histologically ascertained ES patients aged ≥40 years who registered at our institute from 2013 to 2018. Prospectively collected data were analysed for overall survival (OS), event-free survival (EFS) and chemotherapy-related toxicities. Results: There were 66 patients, of which 34 were non-metastatic, and 32 were denovo metastatic, recurrent or had doubtful metastasis. At presentation, median age was 46 years, and 42 (63.6%) had extra-skeletal primary and 24 (36.3%) had extremity tumours. Curative treatment was offered to 40 (60.6%) patients. Significant grade 3/4 toxicities in non-metastatic and metastatic cohort, respectively, were febrile neutropenia (61.3%, 37.5%), anaemia (58.1%, 37.5%), thrombocytopenia (45.2%, 25.0%), peripheral neuropathy (25.8%, 12.5%) and dyselectrolytemia (25.8%, 6.25%). Chemotherapy-related toxicity led to death in three patients in the metastatic cohort, versus none in the non-metastatic patients. The 5 year EFS and OS for non-metastatic cohort were 53.8% and 67.8%, while the same for metastatic cohort were 20.7% and 27.5%, respectively. On multivariate analysis, Eastern Cooperative Oncology Group-performance status >2 and metastasis at presentation predicted poorer EFS and OS. Additionally, raised lactate dehydrogenase, larger tumours (>8 cm) and palliative intent treatment predicted worse EFS, while extra-skeletal primary and female gender were indicators of worse OS. Conclusions: Older adult ES patients benefit from aggressive multimodality treatment even in LMIC infrastructure. However, careful patient selection, close monitoring and pertinent dose modifications is imperative due to higher propensity for potential toxicities.

Long-Term Clinical Outcomes and Sequelae of Therapy in Early-Stage Orbital Mucosa-Associated Lymphoid Tissue Lymphoma.

INTRODUCTION: Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients. METHODS: We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities. RESULTS: Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%). CONCLUSION: Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.

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

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.

Dynamic model of infected population due to spreading of pandemic COVID-19 considering both intra and inter zone mobilization factors with rate of detection.

Most of the widely populated countries across the globe have been observing vicious spread and detrimental effects of pandemic COVID-19 since its inception on December 19. Therefore to restrict the spreading of pandemic COVID-19, various researches are going on in both medical and administrative sectors. The focus has been given in this research keeping an administrative point of view in mind. In this paper a dynamic model of infected population due to spreading of pandemic COVID-19 considering both intra and inter zone mobilization factors with rate of detection has been proposed. Few factors related to intra zone mobilization; inter zone mobilization and rate of detection are the key points in the proposed model. Various remedial steps are taken into consideration in the form of operating procedures. Further such operating procedures are applied over the model in standalone or hybridized mode and responses are reported in this paper in a case-studies manner. Further zone-wise increase in infected population due to the spreading of pandemic COVID-19 has been studied and reported in this paper. Also the proposed model has been applied over the real world data considering three states of India and the predicted responses are compared with real data and reported with bar chart representation in this paper.