Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%–15% of all breast cancers in the west. There is a scarcity of data on ILC from the Indian subcontinent. This report intends to present the patterns of care, survival outcomes, and prognostic factors of ILC treated in a tertiary care institute. MATERIALS AND METHODS: This retrospective analysis included consecutive patients diagnosed with ILC and registered at our Institute between 2009 and 2016. RESULTS: We included 97 patients with a median age of 53 years (range 28–80). American Joint Committee on Cancer (7th edition) stage distribution was stage I-8.24%, stage II-45.36%, stage III- 34.10%, and stage IV-12.30%. Bilateral breast cancer was seen in 8 cases. Estrogen receptor, progesterone receptor, and HER 2/neu positivity was 90%, 85%, and 9%, respectively. Triple-negative breast cancer constituted 5% of cases. Twenty-nine events were recorded (systemic and locoregional relapse) with a median follow-up of 3.5 years. Three years relapse-free survival (RFS) and overall survival were 80% and 60%, respectively. Bones were the most common site of metastasis. Age <45 years [HR-1.4 (0.8–2.1), P < 0.001] and advanced clinical tumor stage [T4, HR-2.1 (1.1–3.8), P = 0.001] were associated with poor RFS. CONCLUSION: ILC constituted 2.5% of breast cancer cases at our institute. Triple negativity and HER-2/neu positivity were seen in 9% and 5% of cases, respectively. Age <45 years and advanced clinical tumor stage were associated with poor RFS.

High fms-like tyrosine kinase-3 (FLT3) receptor surface expression predicts poor outcome in FLT3 internal tandem duplication (ITD) negative patients in adult acute myeloid leukaemia: a prospective pilot study from India.

Background & objectives: Mutations in fms-like tyrosine kinase 3 (FLT3) receptor have significant role in assessing outcome in patients with acute myeloid leukaemia (AML). Data for FLT3 surface expression in relation to FLT3 internal tandem duplication (ITD) status and outcome are not available from India. The objective of the current study was to investigate adult patients with AML for FLT3 expression and FLT3 ITD mutation, and their association with long-term outcome. Methods: Total 51 consecutive de novo AML patients aged 18-60 yr were enrolled in the study. FLT3 ITD was detected by polymerase chain reaction (PCR); flowcytometry and qPCR (Taqman probe chemistry) were used for assessment of FLT3 protein and transcript, respectively. Kaplan Meier curves were obtained for survival analysis followed by log rank test. Results: FLT3 ITD was present in eight (16%) patients. Complete remission was achieved in 33 (64.6%) patients. At 57.3 months, event free survival (EFS) was 26.9±6.3 per cent, disease free survival (DFS) 52.0±9.2 per cent, and overall survival event (OS) 34.5±7.4 per cent. FLT3 surface expression was positive (>20%) by flow-cytometry in 38 (88%) of the 51 patients. FLT3 surface expression and transcripts were not associated with FLT3 ITD status. FLT3 expression was significantly associated with inferior EFS (P=0.026) and OS (P=0.018) in those who were negative for FLT3 ITD. Interpretation & conclusions: This study evaluated FLT3 ITD mutation along with FLT3 expression in AML patients, and associated with survival. Negative impact of FLT3 surface expression on survival was observed in AML patients who were FLT3 ITD negative.

A clinicopathological study of primary central nervous system lymphomas & their association with Epstein-Barr virus.

Background & objectives: Primary central nervous system lymphomas (PCNSLs) are relatively uncommon, accounting for 2-3 per cent of primary brain tumours. Majority of these are diffuse large B cell lymphomas (DLBCL) occurring both in immunocompromised and immunocompetent patients. We undertook this study to classify PCNSL into germinal centre (GC) and non-germinal centre (NGC) type based on Hans classification and to find the role of Epstein-Barr virus (EBV) in pathogenesis both by conventional immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). Methods: The consecutive cases of PCNSL during a 10 years period were analysed by IHC for CD45, CD20, CD3, B-cell lymphoma 2 and 6 (Bcl-2 and Bcl-6), B-cell specific octamer binding protein-1 (BOB-1), multiple myeloma oncogene-1 (MUM-1), EBV latent-membrane protein 1 (LMP-1), cyclin-D1, CD10, CD5 and CD23, as well as by CISH for EBV. Results: During a period of 10 years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476) of all intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F) of 1.4:1. Most common location was supratentorial region with predominant involvement of frontal lobe. Single lesions were seen in 38 (58.4%) and multifocal lesions in 27 (41.5%) patients. None of the patients were immunocompromised. All cases were B cell immunophenotype and were DLBCL except one case of follicular lymphoma. According to Hans classification, majority of them were NGC (n=51, 79.6%) and 13 (20.3%) were GC type. Bcl-2 expression was noted in 34 (52.3%) tumours. EBV was positive in three (4.6%) cases; two were detected both by IHC and CISH and one case by CISH only. Interpretation & conclusions: In Indian population, PCNSL occurs mainly in immunocompetent patients, and a decade earlier than in western population. Immunophenotyping revealed that all cases were DLBCL with predominance of NGC type. No prognostic difference was seen between GC and NGC DLBCL. Association of EBV was rare and this virus was possibly not involved in the pathogenesis of PCNSL in immunocompetent individuals. CISH was an easy, economical and less cumbersome method for detection of EBV in PCNSL.

Multiple myeloma presenting with coexisting severe marrow hypoplasia.

A 68-year-old man was referred to us with clinical and bone marrow (BM) features compatible with aplastic anemia. The correct diagnosis, hypoplasia of the BM coexisting with multiple myeloma, became apparent after noting rouleaux in the peripheral blood (PB) and approximately 50% plasma cells in the touch imprint of one of the two BM biopsies done. As standard therapy was precluded, the patient was put on dexamethasone but died within 4 days. This first case of the coexistence of untreated myeloma with aplastic BM shows that even apparently straightforward hypoplasia seen on the BM biopsy should be interpreted in conjunction with the PB smear and the BM touch imprint findings. Among other things, the BM biopsy and imprint should be repeated if the PB has findings such as rouleaux that do not fit with straightforward aplastic anemia. The combination of myeloma and BM aplasia precludes standard therapy and is rapidly fatal.

Pelger-Huet anomaly: a case report.

Impaired lobulation of neutrophils together with exaggerated clumping of chromatin, characteristic of Pelger-Huet anomaly was seen as an incidentalfinding in a 43-year old man who presented with depression. Peripheral blood and bone marrow findings and cytochemistry of the abnormal cells are described and the disease entity discussed.

Melphalan and dexamethasone for patients with multiple myeloma who are not candidates for autologous stem cell transplantation.

BACKGROUND: Multiple myeloma is a disease for which a number of treatment options are available. The choice of therapy is often based on factors such as cost, ease of administration and faster response as the survival rates are similar with most of the regimens. We assessed the efficacy of a combination of melphalan and dexamethasone as first-line therapy in patients with multiple myeloma who were not candidates for autologous stem cell transplantation. METHODS: Thirty-four patients with multiple myeloma were included in the study. Patients received a maximum of 12 cycles of chemotherapy consisting of oral melphalan 8 mg/m2 on days 1-4 and oral dexamethasone 40 mg on days 1-4 and days 9-12 every 4 weeks. Patients were assessed for response on the basis of M proteins and a bone marrow biopsy with touch preparation. RESULTS: The median follow up of surviving patients was 40 months. Nine patients (26.1%) had complete response/near complete response (5 had negative immunofixation) and 15 (44%) had partial response. The regimen was well tolerated and there were no therapy-related deaths. The 3-year overall and progression-free survival rates using the Kaplan-Meier method were 53% and 34%, respectively. The median duration of overall and progression-free survivals were 58 and 28 months, respectively. CONCLUSION: The combination of melphalan and dexamethasone is safe and effective in patients with multiple myeloma who are not candidates for autologous stem cell transplantation.

Primary gastrointestinal non Hodgkin's lymphoma chemotherapy alone an effective treatment modality: experience from a single centre in India.

BACKGROUND: Gastrointestinal tract (GI) is the most frequently involved extra nodal site in non-Hodgkin's lymphoma (NHL). Surgery, radiotherapy and chemotherapy (CT) have been used mostly in various combinations, but lately chemotherapy alone has emerged as an effective option. The purpose of this study is to evaluate efficacy of CT alone in treatment of primary GI-NHL and to compare the results with combined CT+surgery. SETTING AND DESIGN: Retrospective analysis of case records of GI NHL patients. MATERIALS AND METHODS: Over a 15-year period (1986-2000), 77 new cases of primary GI-NHL were registered at our center. GI-NHL was defined according to standard criteria. All patients received chemotherapy. RESULTS: The median age was 32 years (Range 9-80). Endoscopy / CT guided biopsies were performed in 42% (32) of patients for the purpose of diagnosis. Laparotomy was done in 58% (45) of patients to establish a diagnosis or as primary or debulking treatment. Stomach and intestines were involved in 47% (36) and 53% (41) patients respectively. Early stage disease was present in 37% (29). Seventy eight percent of tumors were intermediate to high grade, 43% (33) received only CT while 57% (44) received CT+surgery. Five years EFS and OS were: 72% and 65% for all patients; 72% and 67% for CT only group; 60% and 64% for CT+surgery group (P=.05). Four patients died of neutropenic infection. CONCLUSION: Organ-preservation strategy using chemotherapy alone (CT) can be successfully employed in a significant number of patients with primary GI-NHL.

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy.

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings.

Clinical features and prognostic factors of early breast cancer at a major cancer center in North India.

BACKGROUND: Data on the clinical profile of early breast cancer (EBC) from India is scant. Due to differences in genetics, environment, lifestyle, socio-demographic structure and ethnicity, the presentation and behavior of breast cancer in India may be different. AIMS: To analyze the clinical presentation and outcome of EBC patients. SETTINGS AND DESIGN: A single center retrospective study. MATERIALS AND METHODS: Data from 487 EBC patients registered and treated at our institute from 1993 through 1999 were analyzed. Cox's multivariate regression test was used to determine prognostic factors for overall and disease-free survival (OS & DFS). RESULTS: The median age was 47 years and 49.7% patients were pre-menopausal. Ninety-six per cent patients presented with a lump. Stages I, IIa, and IIb comprised 7.8%, 38.8%, and 47.6% respectively. Only 11.3% patients opted for breast-conserving surgery (BCS) while the remaining 88.7% underwent modified radical mastectomy (MRM). Adjuvant chemotherapy was administered to 275 (56.5%), and radiotherapy to 146 (29.9%). Estrogen receptor status was known in 173, of whom 93 (53.7%) were positive. Most patients were prescribed Tamoxifen for 5 years. At a median follow-up of 48 months, 126 (25.9%) patients had relapsed (systemic 107, loco-regional 19) and 94 (19.3%) had died. Five-year DFS and OS were 73% and 78%, respectively. On multivariate analysis, four positive nodes adversely influenced survival (P< 0.01). CONCLUSIONS: The median age at presentation was 47 years, significantly lower than most Western figures. The majority (86.4%) had a lump size > two cm. BCS was done in only 11% and the rest underwent MRM. Nodal involvement was the significant prognostic factor.

Patient profile and treatment outcome of rectal cancer patients treated with multimodality therapy at a regional cancer center.

BACKGROUND: Incidence of rectal cancer has wide geographical variation. Disease pattern in developing countries is different from developed countries as majority of the patients present in advanced stage because of delayed referral and lack of uniform treatment practices. AIMS: Present study describes the patient profile and treatment results from a tertiary care cancer center in India. SETTING AND DESIGN: Tertiary care Regional cancer center. Retrospective analysis 89 patients with rectal adenocarcinoma treated between 1995 and 2002 were analyzed. METHODS: Patients with adenocarcinoma rectum were evaluated in a G.I. Oncology clinic and were treated using multimodality protocols involving surgery, radiotherapy and adjuvant chemotherapy. STATISTICAL ANALYSIS: A descriptive analysis of patient and disease profile, treatment patterns and out come was performed. Survival analysis was performed using Kaplan-Meier method. RESULTS: Mean age of the patients was 45.4 years and majority of them had tumor in lower third of rectum with evidence of extrarectal spread. Seventy five percent of the patients underwent curative resection with abdominoperineal resection being the commonest procedure. Forty seven percent of patients were given short course preoperative radiotherapy and the remaining received postoperative radiotherapy. Sixty four percent of patients could complete planned adjuvant chemotherapy. Operative mortality was 2% and 23% had morbidity. Local recurrence rate was 8.9%. 5-year disease free and overall survival was 54% and 58% respectively. CONCLUSION: Majority of rectal cancer patients present with locally advanced and low rectal growths leading to low sphincter salvage rates. Despite the advanced stage of presentation optimal oncologic results can be obtained by using a good surgical techniques in combination with adjuvant radiotherapy and chemotherapy. Short course preoperative radiotherapy seems to be more feasible in Indian context. Timely referral and uniform treatment guidelines throughout the country are needed for optimal management of rectal cancer in India.

Etoposide, vinblastine, adriamycin and prednisolone (EVAP) combination chemotherapy as first-line treatment for Hodgkin's disease.

BACKGROUND: Mechlorethamine, vincristine, procarbazine, prednisolone (MOPP) and doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) are well established first-line chemotherapy protocols for the treatment of Hodgkin's disease. The aim of this study was to try a new combination of drugs that individually have a proven efficacy in Hodgkin's disease but have less incidence of severe nausea, vomiting, pulmonary toxicity and sterility. METHODS: This prospective, single-arm study enrolled 66 newly diagnosed, previously untreated patients of Hodgkin's disease with stages IA (bulky)-IVB disease. They were given 6-8 courses of etoposide, vinblastine, doxorubicin and prednisolone (EVAP) as first-line chemotherapy between January 1992 and December 1997. Radiotherapy (RT) was given to the involved fields of those patients who had bulky (> or = 10 cm) stages I or II disease at presentation. The end-points were (i) complete and overall response; (ii) disease-free and overall survival; and (iii) toxicity. RESULTS: Complete response was seen in 78.8% and partial response in 12.2% of patients; the overall response rate was 91%. The median follow up was 48 months. The 5-year overall and disease-free survivals were 72% and 62%, respectively. There were 3 episodes of grade IV neutropenia requiring hospitalization. One patient developed avascular necrosis of the femur. There were 2 deaths during treatment, one due to chemotoxicity, and another due to progressive disease. CONCLUSION: The overall and complete responses were fractionally inferior to the recently published hybrid MOPP/ ABV combination and that of ABVD chemotherapy. The advantages of the EVAP combination are absence of pulmonary toxicity, markedly lower incidence of sterility and nausea and vomiting. EVAP is an attractive option and a randomized trial is warranted to assess its efficacy against established protocols.