Loknatha Dasappa

The Efficacy, Safety, and Cost Benefit of Olanzapine versus Aprepitant in Highly Emetogenic Chemotherapy: A Pilot Study from South India

Background. The efficacy, safety, and cost benefit of olanzapine (OLN) when compared to aprepitant (APR) in the prevention of chemotherapy induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) were evaluated. Methods. A prospective pilot study was done in chemotherapy-naive patients receiving HEC to compare OLN versus APR along with palonosetron and dexamethasone. 100 patients consented to the protocol and were randomized and evaluated for Complete Response (CR) (no emesis, no rescue). Results. CR was 86% for the acute period, 86% for the delayed period, and 80% for the overall period in 50 patients receiving the APD regimen. CR was 84% for the acute period, 88% for the delayed period, and 78% for the overall period for 50 patients receiving the OPD regimen. Patients without nausea were APD: 88% acute, 84% delayed, and 84% overall, and OPD: 84% acute, 88% delayed, and 84% overall. There were no significant grade 3 or 4 toxicities. OPD was comparable to APD in the control of CINV. Conclusion. In this study, there was no significant difference between olanzapine and aprepitant in preventing CINV with highly emetogenic chemotherapy. Olanzapine may thus be used as a potential, safe, and cost beneficial alternative to prevent nausea and vomiting in HEC.

Clinicopathological Profile of Pure Neuroendocrine Neoplasms of the Esophagus: A South Indian Center Experience.

Purpose. Neuroendocrine neoplasms (NENs) of the esophagus are very uncommon with only a few studies published worldwide. Studies on clinical profile, management, and outcomes are very uncommon. Methods. We report the largest single institution retrospective review of 43 patients of pure esophageal NENs out of our registry of gastrointestinal neuroendocrine tumors treated between 2005 and 2014. Data on the incidence, tumor location, clinical symptoms, stage at presentation, grading, treatment protocol, and treatment outcomes was collected and analyzed. Results. Among 1293 cases of esophageal cancers, pure esophageal NENs were diagnosed in 43 cases. The mean patient age was 55.8 years. The male : female ratio was 1.5 : 1. 81.4% of the tumors were located in the lower third of the esophagus and gastroesophageal junction. Neuroendocrine carcinomas (NEC; G3) accounted for the vast majority of NENs (83.7%). 53.5% patients were Stage IV and 32.5% were Stage III at presentation. The combined median survival of stages II and III patients was 18.25 months, with treatment. The median survival of treated patients with metastatic disease was 6.5 months. Conclusion. Esophageal NENs most commonly were neuroendocrine carcinomas, presented in metastatic stage and were associated with poor prognosis. Grade 2 (G2) tumors had better outcomes than NEC (G3). In nonmetastatic disease, presence of lymph node metastasis and unresectable disease had poorer outcomes.

Current status of systemic therapy for recurrent and/or metastatic squamous cell carcinoma of the head and neck

Head and neck squamous cell carcinoma (HNSCC) is now the seventh most common cancer worldwide. The median overall survival for patients with recurrent and/or metastatic (R/M) HNSCC remains <1 year despite modern systemic chemotherapy and targeted agents. Palliative systemic therapy for patients with R/M HNSCC typically includes a platinum-based doublet, with an understanding that the increase in efficacy compared with single agents is primarily related to improved response rate, and not survival. Till date, the only systemic therapy regimen to demonstrate survival superiority over platinum-5-fluorouracil (5-FU) doublet is platinum, FU, and cetuximab. Epidermal growth factor receptor inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only a modest success in R/M HNSCC. Immunotherapy represents an attractive treatment option for R/M HNSCC, with encouraging preliminary data from studies involving immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab) and toll-like receptor agonists (e.g., motolimod). Given the poor prognosis of R/M HNSCC, enrollment of patients into clinical trials to investigate novel systemic agents, is necessary for further improvement of oncologic outcomes in this patient population.

Dual mutations and complex mutations in metastatic nonsmall cell lung cancer: A single-institution experience from South India

Wide use and incorporation of newer diagnostic tools in the management of metastatic nonsmall cell lung cancer (NSCLC) has helped in achieving the goal of personalized treatment of this disease. With the wide use of polymerase chain reaction and fluorescence in situ hybridization increasing number of patients are being diagnosed with dual and complex mutations posing a new challenge in the management of patient with metastatic NSCLC. In this article, we would like to bring forth six such cases and the varied responses to the current available treatment in patients with complex and dual mutations. The appropriate management in these groups of patients is yet to be standardized.

Efficacy and safety of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil regimens in locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma: A prospective phase II study from South India

BACKGROUND Patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma have a poor prognosis. The maximum benefit of systemic chemotherapy is usually achieved in the first-line setting. Even though systemic chemotherapy has been used for long time, in view of unsatisfactory results, no standard regimen has been emerged. Unfortunately, till date, there is no published prospective data from India, comparing the two most commonly used triplet regimens, epirubicin, cisplatin plus 5-fluorouracil (ECF) and docetaxel, cisplatin plus 5-fluorouracil (DCF), in this patient population. MATERIALS AND METHODS The present study aimed to compare the efficacy and safety of the first-line systemic chemotherapy with ECF and DCF regimens in locally advanced inoperable or metastatic gastric or GEJ adenocarcinoma. The primary endpoint was overall survival (OS). The secondary endpoints were overall response rate, progression-free survival (PFS), and toxicity profile. RESULTS Between January 2015 and December 2016, 58 patients were assigned and treated with ECF (n = 30) or DCF (n = 28) regimens. The median OS was 9.4 months with ECF and 12.5 months with DCF regimen (log-rank, P = 0.000), while median PFS was 5.8 and 7.5 months, respectively (log-rank, P = 0.002). Patients in the DCF arm had more frequent reductions in chemotherapy doses than those of the ECF arm (28.6% vs. 16.7%; P = 0.54). As compared with the ECF, the DCF regimen was associated with more frequent Grades 3-4 toxicities-neutropenia (16.7% vs. 39.3%, P = 0.17), febrile neutropenia (13.3% vs. 25%, P = 0.52), mucositis (6.7% vs. 17.8%, P = 0.43), and diarrhea (6.7% vs. 14.3%, P = 0.67). CONCLUSIONS In comparison to ECF, the DCF regimen was associated with a statistically significant 3.1 months longer median OS without any significant increase in Grades 3-4 toxicities. DCF can be considered as one of the reference regimens, in properly selected patients with advanced/metastatic gastric or GEJ adenocarcinoma.

Ki-67 and subtype as prognostic and predictive markers of diffuse large B-Cell lymphoma

Quick Response Code: Abstract Introduction: Since patients with similar International Prognostic Index (IPI) scores have varied outcomes, molecular signatures including Ki‐67 overexpression have been studied to prognosticate diffuse large B‐cell lymphoma (DLBCL), which have shown varied outcomes. Objective: To correlate Ki‐67 expression with survival in two biologic subgroups of DLBCL. Materials and Methods: One hundred and twelve adults with DLBCL between 2008 and 2012 were identified. Ki‐67 overexpression was determined using immunohistochemistry. Results: A total of 112 patients of DLBCL were identified and included in the study. The median age was 54 years (18–78 years), with a male/female ratio of 1.8:1. Median survival was greater in patients with low Ki‐67 (n = 32) as compared to high Ki‐67 (n = 44) (32 m vs. 21.5 m, P = 0.033). In the germinal center B‐cell (GCB) subtype, low Ki‐67 had a better survival as compared to high Ki‐67 (35 m vs. 28 m, P = 0.044), whereas in the non‐GCB (NGCB) subtype, the results were same but statistically insignificant (26.5 m vs. 18 m, P = 0.7). In the high IPI arm, low Ki‐67 had a better survival (26.5 m vs. 17 m, P = 0.02), whereas in low IPI arm, the results were similar but statistically insignificant (39 m vs. 38 m, P = 0.837). Survival analysis was done in each treatment arm (CHOP and R‐CHOP) based on Ki‐67 expression (high or low) in GCB and NGCB arms. No statistically significant difference was noted in any of the four arms; 27.5 m versus 34 m (P = 0.738) in high versus low Ki‐67 in CHOP‐GCB arm, 15 m versus 22 m (P = 0.443) in high versus low Ki‐67 in CHOP‐NGCB arm, 27 m versus 44 m (P = 0.104) in high versus low Ki‐67 in R‐CHOP‐GCB arm, and 31 m versus 35 m (P = 0.861) in high versus low Ki‐67 in R‐CHOP‐NGCB arm. Conclusions: Ki‐67 although an indicator of poor outcome, its use to predict outcomes alone in the absence of study of expression of concomitant markers such as myc/BCL6 would cause a bias in results. Furthermore, its relevance in the rituximab era needs further validation.

Colorectal cancer presenting as ovarian metastasis

Background: Metastatic malignant tumors account for up to 7% of ovarian masses. Approximately 3.6% to 7.4% of patients with colon cancer have ovarian metastasis at the time of initial presentation, of which 45% are mistaken for primary ovarian tumors. Methods: Tumor registry was analyzed retrospectively for the cases of colorectal cancers diagnosed between 2008 and 2013. SPSS version 19 was used for statistical analysis. The survival curves were generated using the Kaplan–Meier method using log-rank test. Results: A total of twenty such patients were identified. Median age was 40 years (22–60 years). Seventeen (85%) patients were below 50 years. Most common symptom was abdominal pain (n = 11; 55). Carcinoembryonic antigen was elevated in 17 (85%) patients and CA-125 in 15 (75%) patients. Involvement of ovary was bilateral in almost half of the patients (n = 11; 55%). Median overall survival was 8 months. It was significantly higher in six patients with ovary-only metastasis as compared to extraovarian involvement, 24 versus 4 months, respectively (P = 0.001). Other factors such as extent of extraovarian metastasis, hepatic and peritoneal involvement, and administration of postoperative therapy did not have a significant survival implication. Conclusion: A female patient, especially in the premenopausal age, presenting with a pelvic mass should always be suspected for ovarian metastasis from colon cancer, and necessary evaluation should be carried out. Postoperative chemotherapy (5-fluorouracil-based or capecitabine-based) should be incorporated in suitable patients. However, further larger studies are required in this regard.

Plasmablastic lymphoma of the gastrointestinal tract: A rare entity with a dismal prognosis

INTRODUCTION Plasmablastic lymphoma (PBL) is a rare and aggressive type of mature B-cell lymphoma, which is usually associated with HIV infection. The most common site of PBL is the oral cavity. Involvement of the gastrointestinal (GI) tract is rare, and literature is limited to few case reports and case series. AIMS To retrospectively analyze the presentation, clinical findings, and outcome of patients presenting to our institute with a diagnosis of PBL involving the GI tract. MATERIALS AND METHODS A retrospective observational study was conducted at our institute from February 2008 to January 2015 on consecutive patients presenting with PBL involving the GI tract. The data were compared to various case reports and series published in peer-reviewed journals. RESULTS There were four patients diagnosed with PBL of the GI tract; three male and one female. The location of involvement was in the stomach, ileocecal junction, ascending colon, and rectum. Only one patient was HIV-positive and was on combination antiretroviral therapy since 2 years. Among the three immunocompetent patients, only one survived with therapy; however, the patient relapsed within 6 months of completion of treatment. CONCLUSION PBL was seen to have a uniformly aggressive clinical course with poor outcomes even with optimal treatment. The prognosis of immunocompetent patients appears to be worse than that of HIV-AIDS patients. Although the most common histologies seen with GI lymphomas are mucosa-associated lymphoid tissue type lymphomas or diffuse large B-cell lymphoma, rarer and more aggressive histologies like PBL need to be kept in mind.

Clinical profile, treatment, and outcomes of patients with mantle cell lymphoma treated in a tertiary care center in South India

Introduction: Mantle cell lymphoma has an aggressive course, with unfavorable outcomes. Subjects and Methods: A retrospective analysis was undertaken and 77 cases were identified between 2009 and 2014. Results: Median age was 55 years with a male to female ratio of 6:1. Patients with pure nodal disease at presentation were fewer than with extranodal disease (53.2%). Most common extranodal site was bone marrow. A number of patients with low-, low-intermediate, high-intermediate, and high-risk International Prognostic Index (IPI) scores were 6, 24, 22, and 25. Treatment consisted of cyclophosphamide,hydroxydaunorubicin, oncovin, prednisolone (CHOP) or R-CHOP regimens. Median survival was 21 months. Median overall survival with early and advanced disease was 31 and 18 months (P = 0.02). Patients who received R-CHOP survived better than those given CHOP, 30 and 16 months (P = 0.0002). There was no difference in survival with respect to age, gender, extranodal, or bone marrow involvement. Conclusions: Most patients presented with extranodal disease, advanced stage, and high IPI. Although rituximab has improved survival, intensive chemotherapy would be required to improve survival.

Outcome of young adults with chronic myeloid leukemia treated with upfront imatinib: A single institutional experience

Background: Young adult patients with malignancy are a distinct group of the population. In addition to their ailment, psychosocial issues including fertility issues should be addressed. Chronic myeloid leukemia (CML) is a disease of the elderly population. The outcome with imatinib in young population is not known. Aim: To study the clinical profile and outcome of young patients newly diagnosed with CML on imatinib and to compare with those of elderly population in a tertiary cancer center. Materials and Methods: 369 patients with newly diagnosed CML were included in the study. Patients belonging to the age group of 20–39 years were used as the study group and those who were more than 40 years were used as controls. Both the groups were treated with imatinib. They were followed up for a period of 3 years. Milestones in terms of achieving hematological, cytogenetic and molecular responses were noted. Toxicity profile of the imatinib and the compliance of the patients were also recorded. Results: A total of 173 patients were in the study group and 196 patients were in the control group. Rates of achieving a hematological response at 3 months (94.2% vs. 93%), the complete cytogenetic response at 12 months (68% vs. 61%) and major molecular response at 18 months (72.2% vs. 67.6%) were among the study group and control group, respectively. None of them were statistically significant. Three years event free survival among the study group and the control group was (85.2% vs. 83.4%) respectively; however, the difference did not reach statistical significant value. Conclusion: This study shows that the outcome of young adults with CML is comparable to those of the elderly people with imatinib both in terms of response rates and survival.