Background: The treatment of primary CNS lymphoma (PCNSL) comprises high dose Methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy(WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in patients with PCNSL. Methods: We screened 35 patients & enrolled 24 patients with PCNSL in a phase II trial. They underwent 5 two-weekly cycles of MVP chemotherapy with HDMTX, Vincristine & Procarbazine. Rituximab was added in 16 patients as per their preference & affordability. Patients with complete response (CR) to induction chemotherapy were given reduced dose WBRT 23.4Gy/13fractions/2.5weeks while those with partial response (PR), stable or progressive disease(PD) were given standard dose WBRT 45Gy/25fractions/5 weeks. Thereafter 2 cycles of consolidation chemotherapy with Cytarabine was given. The primary endpoints of the study were assessment of response rate & progression free survival (PFS). The secondary endpoints were assessment of overall survival (OS), toxicity profile, serial changes in quality of life & neuropsychological parameters. Results: The median age at diagnosis was 50 years. Out of 20 patients who completed induction chemotherapy, 10(50%) achieved CR, 9(45%) had PR & 1 patient had PD. After a median follow-up period of 21.05 months, the median OS and PFS had not been reached. The actuarial rates of 3 year PFS & OS were 51% & 51.4% respectively. 4 patients in reduced dose WBRT arm had recurrence & 2 of them died of PD, whereas there was one recurrence and no cancer related death in standard dose WBRT arm. On univariate analysis of PFS, age60 years(p ¼ 0.004) & use of standard dose WBRT (p ¼ 0.047) led to significantly improved outcome. Serial neuropsychological assessments showed marked improvement in general cognition, verbal fluency & motor speed after induction chemotherapy & treatment completion. Conclusions: In patients with newly diagnosed PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression & early death.
Introduction In India, patients with gastric cancer present at an advanced stage, and there is no standard chemotherapy regimen. Al-Batran's fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy gave us a glimmer of hope.
Objectives Hence, we intended to evaluate the efficacy of FLOT chemotherapy in locally advanced and metastatic adenocarcinoma of stomach.
Materials and Methods In this single-center, prospective cohort, patients with locally advanced and metastatic gastric adenocarcinoma who required chemotherapy between March 2016 and November 2017 were included in the study. All patients received standard FLOT chemotherapy. The primary objective was to evaluate the safety and efficacy of FLOT chemotherapy in the Indian population. Overall survival (OS) and progression-free survival (PFS) were calculated through the plotted Kaplan–Meier curves.
Results In our study, 28 patients received FLOT chemotherapy. Their mean age was 55 years (range, 28–70 years) with a male preponderance (89.3%). Twenty-five patients had metastatic disease (89.3%), and three had locally advanced disease (10.7%). The median number of cycles was 4.5 (range, 1–8), and 75% received at least four cycles (n = 21). The hematological toxicities exhibited were neutropenia (50%) and febrile neutropenia (35.7%). Sixteen (57.1%) patients needed dose modifications due to treatment-related adverse effects (AEs). AEs led to treatment discontinuation in seven (25%) patients after the first cycle. The overall response rate in the intent-to-treat population was 52.7%, with the best-obtained response being a partial response, median PFS of 5 months, and median OS of 13 months.
Conclusion FLOT chemotherapy regimens induced excellent responses but with significantly increased toxicity, needing dose modifications, and hence, should be considered only in a young and fit patient.
e12033 Background: There is increasing evidence that obesity is strongly associated with breast cancer (BC) and has a major impact on the patient tolerance, overall survival (OS) and progression free survival (PFS). Chemotherapy dosing as per body surface area (BSA) or the actual body weight is a major dilemma among the oncologists. Moreover, the side effects of chemotherapy in obese patients in an Indian population has not been described previously in literature. We intended to evaluate the major toxicity, OS and PFS in obese BC patients who received adjuvant chemotherapy (ADC) with Adriamycin/cyclophosphamide (AC) and paclitaxel (T). Methods: A retrospective analysis of 331 patients of BC who received 4 cycles of adjuvant AC + T from a single tertiary centre in South India between 2006-2014 were included . All patients were treated as per their BSA which were capped at 2. Body Mass Index (BMI) was divided into normal (18-22.99), Overweight (23-24.99) and Obese ( ≥25 as per Asian guidelines). The toxicity was scored as per NCI-CTCAE criteria. Results: Out of 331 patients, 213 were obese. On comparison of normal and over weight with obese patients, 65 (30.5%) in obese group had significant all grade neuropathy (p = 0.027), 65 (30.5%) had Grade 2 and 3 myelosuppression (p <0.001), 31 (14.5%) had all grade emesis (p = 0.031) and 28 (13.1%) had myalgia (0.001). The 5 year OS and PFS were 93.7% and 82.3% respectively in obese patients, higher than the patients with normal weight with a 5 year OS and PFS of 92.4 % and 76.9% , but was not statistically significant. Conclusions: Higher rates of severe toxicities were seen in obese BC patients who received ADC as per their BSA. The 5 year OS and PFS was better in obese BC patients, but was not statistically significant. [Table: see text]
e15608 Background: Lipocalin2 (LCN2, also known as neutrophil gelatinase-associated lipocalin) is a protein that in humans is encoded by the LCN2 gene. Its abnormal expression serves critical roles in EMT transition, angiogenesis, cell migration and invasion in many cancers. We aim to assess the in vitro and in vivo effects of LCN2 as a potential chemo and radiosensitizer. Methods: Normalized RNAseq RSEM values of LCN2 were compared between normal and tumour samples from TCGA. Differences between median expression levels were assessed using Wilcoxon rank sum test. Kaplan-Meier model was used for survival analysis. Immune cell population in publicly available Colon Adenocarcinoma dataset was estimated using MCP Counter tool. Cell systems used to experimentally study the role of LCN2 in therapy resistance and tumor progression were HCT116, HT29 and DLD1. PKP3 and/or LCN2 were knocked down by shRNA. Tumor regression and therapy (5FU and radiation) sensitivity upon Anti-LCN2 treatment were demonstrated in Xenograft mouse models. Results: Analysis of 23 TCGA datasets containing gene expression data for both tumour and adjacent normal samples indicated that LCN2 levels are elevated in colon tumors. Colon cancer cell line HCT116 derived PKP3 knock-down or LCN2 over-expressing cells showed therapy resistance. A comparison of the tumor cell lines HCT116, HT29 and DLD1 show that increased LCN2 expression correlates with therapy resistance. LCN2 levels correlated with resistance to 5FU (p = 0.006) and its ability to clear ROS (p < 0.05) in vitro. Inhibiting LCN2 led to a decrease in invasion in vitro (p = 0.0005), increased sensitivity to 5FU in vitro (p = 0.001) and inhibition in tumor growth and increased sensitivity to 5FU and radiation (p = 0.005) in xenograft mouse models. On MCP counter analysis of TCGA, in Colon adenoca the normal samples show a correlation between LCN2 expression and T-cells (Pearson r = 0.45, p = 0.0028) and with the T-cell chemoattractant CXCL10 (Pearson r = 0.5, p < 0.0001). Such correlations are broken in tumour samples. Conclusions: LCN2 expression leads to chemo and radio resistance in colon cancer cell lines and xenograft mouse models. Inhibiting LCN2 function can inhibit tumor progression and sensitizes tumors to radiation and 5FU. These results suggest that LCN2 expression could be a marker that can be used to determine the choice of therapy offered to patients and that LCN2 could serve as a therapeutic target that sensitizes cells to radio and chemotherapy. LCN2 affects tumor progression and therapy sensitivity probably through T cell mediated immune pathway.
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