Ah Rudresha

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.

Study of clinical, haematological and cytogenetic profile of patients with acute erythroid leukaemia.

Background Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting <5% of all the cases of AML. The World Health Organization (WHO) in 2001 classified AEL into two types: (1) erythroid/myeloid leukaemia which required ≥50% erythroid precursors with ≥20% of the non-erythroid cells to be myeloid blasts and (2) pure erythroleukemia (pEL) with ≥80% erythroblasts. The WHO 2008 classification kept these subcategories, but made erythroleukemia a diagnosis of exclusion. There are very few studies on the clinico haematological and cytogenetic profile of this disease, considering the rarity of its occurrence and poor prognosis. Materials and methods This study was done by retrospective analysis of data from 32 case files of patients diagnosed with AEL. Clinical details noted down were the demographic profile, peripheral blood smear details and bone marrow examination details: (1) blasts-erythroblasts and myeloblasts, (2) dysplasia in the cell lineages and (3) cytogenetic abnormalities. Results The most common presenting symptom was fever. Pancytopenia at presentation was seen in 81.25% of patients. Dysplasia was observed in bone marrow in 100% of erythroblasts and in 40% of myeloblasts in erythroid/myeloid subtype. In pure myeloid subtype, myeloid and megakaryocytic dysplasias were not obvious. Complex karyotype was noticed only in patients of pEL. Conclusion AEL is a rare group of heterogeneous diseases with many neoplastic and non-neoplastic conditions mimicking the diagnosis. The clinical presentation and cytogenetics are also non-specific, presenting additional challenges to the diagnosis.

Primary breast angiosarcoma – a single institution experience from a tertiary cancer center in South India

INTRODUCTION Primary angiosarcoma of the breast is a rare entity with incidence of less than 0.05% of all malignant breast neoplasms. It occurs in young females without any associated risk factors. The tumor behaves aggressively and has a poor prognosis compared to invasive ductal carcinoma. METHOD It was a retrospective observational study done at a tertiary cancer center from January 2012 to December 2016. The medical records of patients diagnosed with primary breast angiosarcoma were reviewed for the study. Clinicopathological profile, treatment, and the outcomes were analyzed. RESULTS Four patients were diagnosed with primary breast angiosarcoma out of 2560 breast cancer patients seen over a period of 5 years. Two had metastatic disease at presentation. Among four patients, two underwent surgery of the primary tumor, whereas, all received chemotherapy either as adjuvant or palliative setting. One patient received adjuvant radiation therapy. Three patients received 2nd line and one received 3rd line chemotherapy on disease progression. After a median follow-up of 18 months one patient was surviving on 3rd line chemotherapy with trabectedin. Other three succumbed to disease after progression. CONCLUSION Due to a small number of this malignancy randomized studies are difficult to perform and optimum treatment strategy still need to be defined.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience

Background: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. Methods: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. Results: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318–0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. Conclusion: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.

Comparison of health-related quality of life with epirubicin, cisplatin plus 5-fluorouracil and docetaxel, cisplatin plus 5-fluorouracil chemotherapy regimens as first-line systemic therapy in locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma: A prospective study from South India

Background: Health-related quality of life (HRQOL) is an important oncologic end point for upper gastrointestinal malignancies. Unfortunately, till date, there is no published prospective data from India, comparing the HRQOL parameters between first-line chemotherapy regimens in advanced/metastatic gastric cancer. Materials and Methods: The present study aimed to compare the HRQOL of first-line systemic chemotherapy with epirubicin, cisplatin plus 5-FU (ECF) and docetaxel, cisplatin plus 5-FU (DCF) regimens in patients with locally advanced inoperable or metastatic gastric or gastro-esophageal junction adenocarcinoma. The secondary end points were overall response rate, progression-free survival (PFS), overall survival (OS), and toxicity profile. Results: Between December 2014 and December 2016, 65 patients were treated with ECF (n = 34) or DCF (n = 31) regimen. The baseline HRQOL scores were comparable between the two study groups, with the exception of significantly poor pain and sleep difficulties symptom score in the DCF group. After three cycles of treatment, both the groups showed improvements in most of the quality of life (QOL) parameters including global QOL score, compared with their baseline status. After six cycles of chemotherapy, the ECF group showed nonsignificant deterioration for most of the QOL parameters; but on the contrary, the DCF group maintained improved scores for most of the QOL parameters. The median survival until a definitive deterioration of global QOL score was significantly better in the DCF arm in comparison to the ECF arm (7.1 vs. 5.6 months, respectively, P = 0.000). The median OS was 9.2 months with ECF and 12.5 months with DCF regimen (P = 0.000), while median PFS was 5.7 and 7.4 months with ECF and DCF regimens, respectively (P = 0.002). Conclusions: This prospective study highlighted a better impact of DCF chemotherapy on the HRQOL of patients with advanced/metastatic gastric cancer and showed the importance of QOL assessments in clinical trials to complement the risk–benefit judgment.

Plasmablastic lymphoma in immunocompetent and in immunocompromised patients: Experience at a regional cancer centre in India

Introduction: Plasmablastic lymphoma (PBL) is a rare lymphoma associated with immunosuppression. It is strongly associated with immunosuppression (human immunodeficiency virus [HIV]) and often occurs within the oral cavity. PBL is also seen in patients receiving immunosuppressive therapy; however, despite its predisposition for the immunocompromised patients, PBL has been diagnosed in immunocompetent patients. Aim: This study aims to prognostic factors and outcome of PBL in immunocompromised and in immunocompetent patients. Materials and Methods: We conducted a retrospective study at our institute from the year 2008 to 2015. Results: A total of 13 patients (8 males and 5 females) with PBL were identified. Eight patients (61.5%) had extraoral PBL (median age 30.2 years) and 5 patients (38.5%) had oral PBL (median age 44 years). Most common extraoral site was gastrointestinal tract. Eight (61.5%) out of 13 patients were HIV positive. More than 50% of patients had Ann Arbor Stage III or IV. All the cases were CD20 negative and CD138 positive. Seven out of 13 patients had Ki-67 more than 80%. Nine patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Three patients were on best supportive care due to poor performance status (PS). One patient received intensive chemotherapy with CODOX-M/IVAC. The median overall survival was 9 months in HIV-positive patients and 6 months in HIV-negative patients. The prognosis was worse in patients with Ki-67 of >80%. Statistical Analysis: Survival curves were generated using the Kaplan–Meier method and analyzed using log-rank test and Fishers t-test. Conclusion: The present study confirms that PBL in both HIV-positive and in HIV-negative patients has an overall unfavorable outcome. The most important prognostic factors are stage, ki-67, and the Eastern Cooperative Oncology Group PS of the patient at the time of presentation.

Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience

Background: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkins lymphoma which occurs in both immunocompromised and immunocompetent patients. It has an overall poor prognosis in spite of a multimodality treatment approach including chemotherapy and radiotherapy. This study attempts to further delineate the clinicopathological, immunohistochemical, and radiological profile of PCNSL at Kidwai Memorial Institute of Oncology, Karnataka, India. Materials and Methods: All the pathologically confirmed PCNSL cases between January 2010 and June 2016, at our center, were analyzed retrospectively. The influence of potential prognostic parameters on overall survival (OS) was investigated by log-rank test and Cox regression analysis. Results: Of the 26 PCNSL patients, 17 (65.3%) were males. Median age at diagnosis was 42.5 years. None of the patients had HIV or Epstein-Barr virus positivity and only four patients (15.4%) had B-symptoms. The most common location in the brain was cerebral hemispheres in 15 patients (57%) and 10 patients (38.5%) had multiple intracranial lesions. Histologically, all were diffuse large B-cell lymphomas, except one case of anaplastic large cell lymphoma. Immunohistochemically, 18 patients (69%) had MUM 1 positivity and 20 cases (77%) belonged to nongerminal center subtype. DeAngelis protocol was followed in 24 patients (92%), and among this cohort, Memorial Sloan Kettering Cancer Center Class 1 (n = 17) and Class 2 (n = 7) patients had a median OS of 25 months and 11 months, respectively. Conclusion: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify more effective primary chemotherapy regimens to further improve the treatment outcome.

Evolution of the treatment of primary central nervous system lymphoma in a Regional Cancer Center of South India: Impact of high-dose methotrexate on treatment outcome

Objective Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin lymphoma. This study attempts to delineate the clinicopathological and radiological profile of PCNSL cases at our center. Materials and Methods All the pathologically confirmed PCNSL cases between January 2007 and July 2016 were analyzed retrospectively. The influence of potential prognostic parameters and therapeutic strategies on survival was investigated by log-rank test and Cox regression analysis. Results Of the 53 PCNSL patients, 34 (64%) patients were males. Median age at diagnosis was 44 years (range 22-65 years). The most common location in the brain was the cerebral hemispheres in 32 patients (60%), and 16 patients (30%) had multiple intracranial lesions. Histologically, all patients were diffuse large B-cell lymphomas, except one case of anaplastic large-cell lymphoma. The median survival of the patients received whole-brain radiation alone ( n = 6), standard CHOP chemotherapy + radiation ( n = 14), and DeAngelis protocol ( n = 31) was 8 months, 13 months, and 23 months, respectively. Among the 31 patients treated with DeAngelis protocol, Memorial Sloan Kettering Cancer Center Class 1 ( n = 23) and Class 2 ( n = 8) patients had a median overall survival (OS) of 25 months and 13 months, respectively. The incidence of treatment-related neurotoxicity was significantly higher with DeAngelis protocol, in comparison to CHOP + whole-brain radiation therapy (26% vs. 14%, P < 0.05). Conclusion None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate-based chemotherapy combined with radiation was the only factor, which had a significant impact on survival (log-rank P = 0.000) but at the cost of increased neurotoxicity.

Colorectal cancer presenting as bone metastasis

Introduction: Bone metastasis is a rare site of metastasis, seen in only 3.7–11% of clinical cases. Isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare. Objectives: To discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with survival in patients of colorectal cancer that have bone metastasis at the time of presentation. Materials and Methods: Retrospectively, tumor registry was analyzed for the cases of colorectal cancer presenting with bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan–Meier method and analyzed using the log-rank test. Results: Ten such patients were identified (male:female = 7:3) of the total 410 patients. Median age was 41 years (22–50 years). All patients were < 50 years of age. Median CEA level was 147.5 (45–840). Three patients had bone-only metastasis. Most common metastatic site involved was liver (six patients) and lungs (three patients). The most common sites of bone metastasis were vertebra and pelvis (4 each). Chemotherapy was given in seven patients. Median overall survival was 5.5 months (2–36 months). It was higher in males, in those with bone-only involvement and those without liver involvement. Vertebral involvement, pelvic involvement, CEA levels, and chemotherapy did not show any significant survival implication. Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

Multiple myeloma: Experience of an institute in limited resource setting

INTRODUCTION Multiple myeloma (MM) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The mainstay of treatment of myeloma is induction treatment followed by consolidation with autologous stem cell transplant (ASCT). However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT. AIM To study the epidemiological features and outcome of MM patients treated in a limited resource setting. MATERIALS AND METHODS We conducted a retrospective study at our institute to identify patients diagnosed as MM from 2005 to 2016. We studied the epidemiological profile and the outcome of the treatment in terms of response rates and overall survival. STATISTICAL ANALYSIS Survival analysis was performed using Kaplan-Meier curve. RESULTS Median age at diagnosis is 54 years (range: 39-85 years). IgG myeloma was the most common type seen in 72% of patients. The International Staging System (ISS) was ISS I (31%), ISS II (30%), and ISS III (39%). The median duration of treatment for thalidomide + dexamethasone (TD) and bortezomib + TD (VTD) was 9 and 7 months, respectively. Median survival for the TD versus VTD regimen (in a nontransplant setting) for the ISS I, ISS II, and ISS III groups was 49 and 55 months (P = 0.056), 42 and 48 months (P < 0.05), 21 and 27 months (P < 0.05), respectively. CONCLUSION Proteasome inhibitors significantly improved the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.