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.

Spontaneous pulmonary arterial embolization: A rare complication of the silicon-based peripherally inserted central venous catheter (PICC).

Peripherally inserted central catheters (PICC) are widely used in oncology for administration of chemotherapy. However, sometimes there may be complications associated with them such as infections, thrombosis and rarely fracture of catheter and embolization of the catheter fragments. Here we report a case of 59-year old gentleman with locally advanced carcinoma of head of pancreas, who had spontaneous fracture of a silicon based PICC and later migration of the catheter fragment through the heart and further into the right pulmonary arterial system. The embolized catheter fragment was retrieved through a vascular snare from the right femoral venous route. This case highlights the fact that silicon PICCs are fragile and have a high risk of spontaneous dislodgement and should be replaced by better alternative polyurethane PICCs.

PARP inhibitors in hereditary breast and ovarian cancer and other cancers: A review.

There has been a paradigm shift in the management of cancer, with the immense progress in cancer genomics. More and more targeted therapies are becoming available by the day and personalized medicine is becoming popular with specific drugs being designed for selected subgroups of patients. One such new class of targeted drugs in the armamentarium is Poly ADP Ribose Polymerase (PARP) inhibitors (PARPi), which inhibit the enzyme PARP, thus interfering with DNA repair. This strategy utilizes a pre-existing genomic lesion in tumors with homologous recombination repair defects (including BRCA mutations), weakening tumor cells further by blocking the alternate pathway of DNA repair. In this review, we discuss in detail, the evolution, genetics, mechanism of action, mechanism of resistance, indications of use of PARP inhibitors, as well as combination with other agents and future directions.

Role of 18F-Flurodeoxyglucose Positron-Emission Tomography/Computed Tomography in the Evaluation of Early Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Triple-Negative Breast Cancer.

BACKGROUND: Response evaluation in locally advanced breast cancer is done through different methods ranging from clinical examination to magnetic resonance imaging, however evaluation with positron-emission tomography/computed tomography (PET/CT) in now being incorporated for the response evaluation. The aim of the present study is to correlate response to neoadjuvant chemotherapy (NACT) with PET/CT scan. MATERIALS AND METHODS: The present study is a retrospective analysis of 30 locally advanced, triple-negative breast cancer patients. PET/CT scan was done pretreatment and post three and six cycles of NACT and was correlated with pathologic complete response (pCR). Responding disease was considered when there was at least a 50% reduction in the longest diameter. RESULTS: The median pretreatment size of the breast lesion in CT scan was 3.9 ± 2.3 cm (2-12 cm) and maximum standardized uptake value (SUVmax) on PET/CT was 8.5 ± 5.5 (2.9-24). Among the responders, the median decrease in size of lesion was 3.2 ± 1.3 cm and median reduction in SUV of the tumor among was -8.1 ± 5.4 and was statistically significant when compared with nonresponders (P < 0.001). CT scan has 66% accuracy and PET has 82% accuracy at post three cycles NACT in predicting the pathological response. PET/CT had higher sensitivity and specificity when compared with CT findings alone in response evaluation. CONCLUSION: PET/CT scan can be considered as a sensitive tool for predicting pCRs and further larger trials are required to establish these findings.

Extranodal NK-T Cell Lymphoma, Nasal Type: Retrospective Analysis of Real-World Data.

Peripheral T cell lymphomas constitute nearly 15% of all cases on non-Hodgkin lymphoma. Of these, NK-T cell lymphoma nasal type is a rare and aggressive form. We present our experience of 16 patients of NK/T cell lymphoma which constituted approximately 1% of all lymphoma (N = 1590) cases treated at our center. Male to female ratio was 4.3:1. Median age of presentation was 42 years. Early Stage patients (n = 11) were treated with DeVIC regimen (n = 10) and SMILE (n = 1) chemotherapy and RT to all the patients. Advanced stage patients were treated with SMILE regimen (n = 4) and ICE and local RT (n = 1) with one treatment related mortality. The presence of B-symptoms adversely affected survival. The estimated median PFS and OS were 39 and 49 months respectively. Overall survival was not reached in Limited Stage patients (stage 1 and 2) and 8 months in patients with advanced stage (stage IV) (p = 0.001). According to the new CSWOG staging (retrospectively applied), comparing the Limited versus Extensive Stage, the earlier group has a significantly better estimated PFS (p = 0.020) and OS (p = 0.007). ENKTL is a rare malignancy with aggressive course. B-symptoms portend a poor prognosis to patients with this aggressive lymphoma. The new staging system helps estimate survival better.

Real world experience of treatment and outcome in ALK-rearranged metastatic nonsmall cell lung cancer: A multicenter study from India.

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearranged metastatic non-small cell lung cancer (NSCLC) comprises 5%-7% of all lung cancer and carries a good prognosis with available ALK-inhibitors. Majority of registration trials in ALK-inhibitors did not include Indian patients. Hence, this study was planned to analyze the outcome of Indian patients treated with ALK-inhibitors and associated challenges. METHODS: This is a multi-center study in 5 major tertiary care cancer centers across India treating ALK-rearranged NSCLC patients from April 2013 to April 2019. ALK rearrangement was determined by Ventana immunohistochemistry with D5F3 clone and/or by break-apart FISH. Patients treated with ALK-inhibitors in any lines of treatment were included in this study. Patients were evaluated for clinicopathologic features, patterns of ALK-inhibitors use and outcome. Progression free-survival (PFS) and overall survival (OS) were calculated and data were censored on April 30, 2019. RESULTS: A total of 274 patients were studied, out of which 250 patients received ALK inhibitor and were analyzed further for outcome. The median age was 50 years (range: 24-82) and male to female ratio of 1.17:1. ALK was evaluated by immunohistochemistry in majority of patients (97%), 3 patients by FISH and 3 more patients were evaluated by both methods. Sixty-five percent (n = 162) of the patients received ALK-inhibitor as first line therapy, 51 patients received ALK-inhibitor as switch maintenance therapy after initial chemotherapy. Crizotinib and Ceritinib were used in 88% and 12%, respectively. One patient received Alectinib. Forty-one percent of patients had CNS progression. After median follow up of 27 months (1-72 months), the median OS was 24.7 months with OS rate of 72%, 51%, and 18% at 1, 2, and 4-years respectively. Median OS was 21.2, 26, and 38 months in the first line ALK-inhibitors use (n = 162), switch maintenance group (n = 51) and second line ALK-inhibitors use (postchemotherapy progression) (n = 33), respectively. No baseline variable predicted PFS. Presence of brain metastasis (P = 0.039) and first line ALK-inhibitors use (P = 0.032) emerged as poor prognostic factor for OS on multivariate analysis. PFS rate was 70%, 47%, and 31% at 6, 12, and 18 months respectively. CONCLUSION: This is one of the largest real-world data on outcome of ALK inhibitors in ALK-rearranged NSCLC from Asia. In absence of second line ALK inhibitor, initial chemotherapy followed by ALK-inhibitors (switch maintenance) had better outcome. This fact may be studied in individual patient data meta-analysis. Poor performance status and brain metastases at presentation are poor prognostic factors for overall survival. Second-line ALK inhibitor use crucial for better outcome and access to clinical trials are much needed in Indian patients.

Efficacy and tolerability of nimotuzumab in combination with chemotherapy in recurrent and metastatic squamous cell carcinoma of head and neck at a cancer center in Northern India.

INTRODUCTION: Squamous cell carcinoma of head and neck (SCCHN) account for approximately 30-33% of all cancer and the median survival for recurrent and metastatic(R/M) SCCHN remains less than 1 year despite modern advances in therapy. Chemotherapy, usually single agent remains the backbone of therapy in these patients. EGFR antibodies are being used in (R/M) SCCHN. Nimotuzumab is one such agent that has anti-EGFR action similar to other agents without similar skin toxicity. METHODS: Prospective, interventional, non-randomized study done at Rajiv Gandhi Cancer Institute and Research Centre. A total 124 patients were enrolled and divided into Arm A (Chemotherapy + Nimotuzumab) and Arm B (Chemotherapy) in a ratio of 1:1 i.e., 62 in each arm. They were evaluated and treated as per protocol after a written informed consent. Statistical analysis was done using the SPSS software. Quantitative variables were compared using Unpaired t-test/Mann-Whitney Test. Qualitative variables were compared using Chi-Square test /Fisher's exact test. Kaplan-Meier analysis was used to assess the PFS, with log rank test for comparison between the groups. A p value of < 0.05 was considered statistically significant. RESULTS: The most frequent primary location of tumor was oral cavity (n=38, 69%) and (n=33, 56.9%) in both arms. The overall response rate in Arm A was 38.2% and 19% in Arm B (p= 0.023). The disease control rate in Arm A was 74.5% and 43.1% Arm B (p= 0.0007). The median PFS in Arm A was 5.2 months whereas it was 3.2 months in Arm B (p= 0.009). CONCLUSION: In this study, the combination of Nimotuzumab plus platinum/taxane based chemotherapy was active and well tolerated in Indian patients in R/M SCCHN. Addition of Nimotuzumab to chemotherapy had a response rate of 38.2% and median PFS of 5.2 months are strong arguments for clinically testing this combination.

Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer.

AIMS: To investigate Ki-67 index with regard to its ability to predict achievement of pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in breast cancer patient. MATERIAL AND METHODS: It was a prospective observational study, conducted in Department of Medical Oncology, Rajiv Gandhi Cancer Institute & Research Center (RGCIRC), New Delhi from February 2014 to March 2016. A total of 134 patients with Stage II/III breast cancer who underwent NACT followed by surgery at our center were enrolled and analyzed. Before starting the treatment, clinical, tumor-related and treatment-related factors were recorded. Response evaluation was done clinically and radiologically after completion of NACT and pathologically on the surgical specimen. We calculated Ki-67 cut-off of 35% to label it as high by area under Receiver operating characteristic curve analysis for prediction of pCR. RESULTS: Clinical complete response (cCR) was observed in 35/134 (26.1%) patients while pCR was observed in 32/134 (23.9%) patients. On univariate analysis, higher grade (III), high Ki-67 index (>35%) and number of chemotherapy cycles (>3) were associated with better CCR rates. On multivariate analysis, number of chemotherapy cycles (>3) and high Ki-67 index (>35%) were independent predictive factors. For the predictive factors of pCR, univariate analysis showed grade (III), estrogen receptor/progesterone receptor negativity, HER-2 positivity, number of chemotherapy cycles (>3), TNBC and high Ki-67 index (>35%) to be associated with higher pCR rates. On multivariate analysis, Ki-67 index >35% and HER-2 positivity were the only independent predictive factors of pCR. CONCLUSIONS: We suggest 35% as best cut-off for Ki-67 expression for predicting response to NACT and achievement of pCR. Validation of this cut-off is required in larger studies.