The clinical utility and safety of short-course immune checkpoint inhibitors in multiple tumours-A real-world multicentric study from India.

The real-world data on short course of immune checkpoint inhibitor (ICI) use are sparse and merit exploration. A multicentric observational study on the safety and efficacy of ICI in oncology patients between August 2014 and October 2020 involves 1011 patients across 13 centers in India. The median age was 59 (min 16-max 98) years with male preponderance (77.9%). The predominant cohort received short-course ICI therapy; the median number of cycles was 5 (95% confidence interval [CI] 1-27), and the median duration of therapy was 3 (95% CI 0.5-13) months. ICIs were used commonly in the second and third line setting in our study (66.4%, n = 671). Objective response rate (complete or partial response) was documented in 254 (25.1%) of the patients, 202 (20.0%) had stable disease, and 374 (37.0%) had progressive disease. The clinical benefit rate was present in 456 (45.1%). Among the patients whom ICI was stopped (n = 906), the most common reason for cessation of ICI was disease progression (616, 68.0%) followed by logistic reasons like financial constraints (234, 25.82%). With a median follow-up of 14.1 (95% CI 12.9-15.3) months, there were 616 events of progression and 443 events of death, and the median progression free survival and overall survival were 6.4 (95% CI 5.5-7.3) and 13.6 (95% CI 11.6-15.7) months, respectively, in the overall cohort. Among the immune-related adverse events, autoimmune pneumonitis (29, 3.8%) and thyroiditis (24, 2.4%) were common. Real-world multicentric Indian data predominantly with short-course ICI therapy have comparable efficacy/safety to international literature with standard ICI therapy.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

PARP Inhibitor in Platinum-Resistant Ovarian Cancer: Single-Center Real-World Experience.

PURPOSE: Poly (ADP-ribose) polymerase inhibitors (PARPi) have proven efficacy in treatment of BReast CAncer (BRCA) gene mutation-positive platinum-sensitive ovarian cancers. There is paucity of data for their role in platinum-resistant ovarian cancer (PROC). We report here retrospective analysis of outcome of PARPi treatment in a group of patients including those of PROC. PATIENTS AND METHODS: We analyzed all consecutive patients who received PARPi. The efficacy of PARPi monotherapy was assessed in patients with relapsed high-grade serous ovarian carcinoma with gBRCAm. The drug was procured through compassionate program. Drugs (olaparib and talazoparib) were provided in capsule form. RESULTS: Between July 1, 2015, and June 30, 2019, 28 patients with ovarian cancer received PARPi. At the time of data censoring (September 30, 2019), four (14.3%) patients are still on treatment. Median age was 54.5 years (range, 39-75 years). Median number of previous lines of chemotherapy received was three (range, 1-6). Eleven platinum-sensitive patients received the drug as maintenance (five in complete response and six in partial response after chemotherapy), whereas 17 (60.7%) had platinum-resistant progressive disease while starting the drug. In PROC, objective response rate (complete response plus partial response) was 47%, median progression-free survival was 8.2 months (5.3-11.3), and overall survival was 14.9 months (11.2-18.5). No new side effects were observed. CONCLUSION: This is the first study from India evaluating PARPi in platinum-resistant ovarian cancer. This study suggests that PARPi is a viable treatment option in patients with PROC with gBRCAm. This should be further evaluated in randomized clinical trial.

Multicentric real world evidence with palbociclib in hormone positive HER2 negative metastatic breast cancer in Indian population.

The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2- MBC). Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2- MBC. A multicentric study on the HR+/HER2- MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (p-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3-4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2- MBC.

Prognostic Factors and the Role of Adjuvant Treatment in Periampullary Carcinoma: a Single-Centre Experience of 95 Patients.

PURPOSE: The effect of adjuvant treatment on those undergoing pancreaticoduodenectomy (PD) for periampullary carcinomas (PAC) is not well studied. Most studies employed chemoradiation as the adjuvant modality. We aimed to analyse clinicopathological differences between types of PACs, the prognostic factors and the role of adjuvant therapy (chemotherapy in the majority). METHODS: Patients with PAC who underwent PD from Jan 2011 to Dec 2015 were retrospectively analysed. RESULTS: Ninety-five patients with PAC underwent PD in the study period. Ampullary carcinoma (AC) was the most common. Pancreatic carcinomas (PC) were larger. AC had lower T stage, perineural invasion (PNI) and R1 resections. Median overall survival (OS) was 32.7 months. On multivariate analysis, lymph node ratio (LNR) ≥ 0.2 and advanced T stage adversely affected the OS. Fifty-seven (66.3%) patients received adjuvant treatment, of which 50 had chemotherapy alone. Adjuvant treatment resulted in better OS in patients with T stage ≥ 3, lymph node involvement, LNR ≥ 0.2, lymphovascular invasion, PNI, tumour size > 2 cm, higher grade and distal cholangiocarcinoma. CONCLUSION: In patients of PAC undergoing PD, AC had favourable clinicopathological profile. LNR ≥ 0.2 and advanced T stage adversely affected OS. Adjuvant treatment resulted in significantly better OS in patients with high-risk features.

Upfront pancreaticoduodenectomy in severely jaundiced patients: is it safe?

AIM: The aim of this study was to evaluate the outcomes following upfront pancreaticoduodenectomy (PD) in severely jaundiced (serum bilirubin level ≥15 mg/dl) patients with malignant distal common bile duct (CBD) obstruction. BACKGROUND: Recent studies have failed to show the benefits of preoperative biliary drainage (PBD) before PD. In addition, there is limited data on the impact of upfront PD on perioperative outcomes in severely jaundiced patients. METHODS: We reviewed the prospectively collected data of 177 patients who had undergone PD for the malignant distal CBD obstruction from May 2009 to May 2018. Study subjects were divided into Group A (severely jaundiced patients with upfront PD; n = 20), Group B (patients with serum bilirubin <15 mg/dl and no PBD; n = 88) and Group C (PBD prior to PD; n = 69). Overall morbidity, in-hospital mortality, and postoperative hospital stay were compared. RESULTS: No significant differences were noted between the three groups regarding sex, tumor size and stage, comorbidities, and surgical technique. The intra-operative blood loss was more in severely jaundiced patients as compared to Groups B and C (605 vs. 300 vs. 350 ml, P = 0.0001), but similar operative times, blood transfusions, and rates of post-pancreatectomy leak and hemorrhage. The infective complications were significantly less with upfront surgery. The overall morbidity, in-hospital mortality, and hospital stay were comparable between the three groups. Multiple logistic regression analysis failed to identify both the presence of preoperative jaundice and hyperbilirubinemia ≥15 mg/dl as independent risk factors for post-PD major morbidity. CONCLUSION: Upfront PD can be performed safely in the selected severely jaundiced patients and is associated with significantly lower infective complications.

Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences.

PURPOSE: The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS: This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS: Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)-based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION: This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil–lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor.

We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD).

Recurrent rhabdoid meningioma with lymph node, pulmonary and bone metastases: a diagnostic and therapeutic challenge.

Rhabdoid meningioma is a rare meningioma variant, classified as WHO grade III. Although this tumor is known for its aggressive behavior and poor prognosis, extracranial metastasis is rare. We report the rare case of a 31-year-old patient with rhabdoid meningioma which recurred several times despite gross total resection, radiation therapy, and gamma knife radiosurgery, and the last recurrence was associated with metastases to lungs, lymph node and bone. The patient showed no response to paclitaxel-carboplatin, or vincristine-cyclophosphamide-adriamycin chemotherapy, and succumbed to the disease. Metastases from rhabdoid meningioma prove to be a diagnostic challenge, and treatment for metastatic meningiomas is not optimized, thus necessitating documentation and interdisciplinary consensus on management protocols.

Extrapulmonary Small Cell Carcinoma - a Case Series of Oropharyngeal and Esophageal Primary Sites Treated with Chemo-Radiotherapy.

BACKGROUND: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. MATERIALS AND METHODS: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. RESULTS: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. CONCLUSIONS: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.

Hand foot syndrome associated with standard dose cytarabine.

Hand-foot syndrome, is a side effect of cytotoxic chemotherapy, causes erythema, dysthesias, swelling of palms and soles and sometimes blisters. Rarely, it may ulcerate. The most commonly used drug that frequently causes this reaction is 5-fluorouracil or its prodrug oral capecitabine. High dose cytarabine is known to cause HFS. Here we report a case of HFS caused by standard dose cytarabine.

Follicular dendritic cell sarcoma with paraneoplatic pemphigus: Rare case and a brief review of literature.

Paraneoplastic pemphigus (PNP) is often a fatal autoimmune bullous disease characterized by severe stomatitis, polymorphous skin eruptions, and underlying neoplasms. We describe a patient with PNP associated with follicular dendritic cell sarcoma (FDCS), a rare neoplasm originating from follicular dendritic cells, which are non-lymphoid, non-phagocytic accessory cells of the lymphoid system and play an integral role in regulation of the germinal center reaction and present antigens to B-cells. The presence of rich vascularity around the tumor and few hyalanized vascular follicles found in histopathological examination gives the clue that the tumor might have developed from Castleman's disease (CD). As for the mechanisms by which CD induces PNP, it has been proposed that autoantibodies secreted from the Castleman's tumor play pivotal role. This hypothesis seems to be supported by the present case, in which CD may have triggered both the FDCS and the PNP.

Solitary plasmacytoma: 10 years' experience at All India Institute of Medical Sciences, New Delhi.

Plasma cell dyscrasias account for 1% of all malignancies and 10% of hematological malignancies. About 5% of patients with a plasma cell dyscrasia present with either solitary bone plasmacytoma (SBP) or, less commonly, a soft tissue mass, extramedullary plasmacytoma (EMP) of monoclonal plasma cells. In this study we present the clinical features, management and outcome of 60 patients with solitary plasmacytoma, who constituted 5.6% of 1129 patients with plasma cell dyscrasias treated over a 10-year period at All India Institute of Medical Sciences. Median age was 49 years. Fifty-two had SBP and eight had EMP. Forty-nine (82%) patients received radiotherapy with or without surgical excision or chemotherapy. Five-year event-free survival (EFS) and overall survival (OS) were 45.5% and 91%, respectively. Median EFS and OS were 38 and 122 months, respectively. Five-year survival rates in patients who developed multiple myeloma and those who did not were 81% and 100%, respectively. The median time of progression to myeloma was 21 months.