Metastatic colo-rectal cancer: real life experience from an Indian tertiary care center.

BACKGROUND: No data exist for the long-term outcome of metastatic colorectal cancer (mCRC) from the Southern part of Asia. The primary objective of the study is to evaluate the survival outcome of mCRC from an Indian tertiary care center. The study also aims to highlight the treatment pattern practiced and the unique clinico-pathologic characteristics. METHODS: This is a single-center retrospective observational study done at a large referral tertiary care center in North India. All patients with synchronous or metachronous mCRC who received at least one dose of chemotherapy for metastatic disease, registered between 2003 to 2017 were included. Primary outcome measures were overall survival and progression-free survival and prognostic factors of overall survival. Descriptive analysis was done for the clinicopathological characteristics and treatment patterns. Kaplan Meier method for overall survival and progression-free survival. Cox regression analysis was performed for the determination of the prognostic factors for overall survival. RESULT: Out of 377 eligible patients, 256 patients (68%) had de novo metastatic disease and the remaining 121 (32%) progressed to metastatic disease after initial treatment. The cohort was young (median age, 46 years) with the most common primary site being the rectum. A higher proportion of signet (9%) and mucinous histology (24%). The three common sites of metastasis were the liver, peritoneum, and lung. In the first line, most patients received oxaliplatin-based chemotherapy (70%). Only 12.5% of patients received biologicals in the first-line setting. The median follow-up and median overall survival of study cohort were 17 months and 18.5 months. The factors associated with poor outcome for overall survival on multivariate analysis were ECOG performance status of > 1, high CEA, low albumin, and the number of lines of chemotherapy received (< 2). CONCLUSION: The outcome of mCRC is inferior to the published literature. We found a relatively higher proportion of patients with the following characteristics; younger, rectum as primary tumor location, the signet, and mucinous histology, higher incidence of peritoneum involvement. The routine use of targeted therapies is limited. Government schemes (inclusion of targeted therapies in the Ayushman scheme), NGO assistance, and availability of generic low-cost targeted drugs may increase the availability.

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

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.

Advanced gastrointestinal stromal tumors: 10-years experience from a tertiary care centre.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We aimed to study the pattern of presentation and treatment outcome of advanced GIST patients seen by us in a 10- year period. METHODS: Medical records of GIST patients seen between years 2002-2012 were retrieved from institute as well as database maintained by authors. Patient included in this analysis had metastatic disease and unresectable and/or residual disease after surgery. RESULTS: During the study period 62 patients fulfilled the inclusion criteria but 6 were lost to follow up before treatment and hence 56 patients were analysed. Median age was 45.5 years (range 17-70 years) with a male female ratio of 2:1. Thirty eight (67%) patients had metastatic disease whereas 32% patients had unresectable or incompletely resected disease. The most common primary site was small intestine in 24 (42.8%) which was followed by stomach in 11 (19.6%) patients. The most common site of metastases was liver in 27 (48%) patients. Median tumor size was 12 cm (range 4-50 cm). Thirty two (57%) patients had mitotic counts of > 5/50 HPF. All patients received imatinib. The most common response seen with imatinib was stable disease achieved in 29 (52%) patients. Imatinib was well tolerated by all patients without any drug discontinuation. The 5-year EFS and OS were 35% and 49%, respectively at a median follow up of 55 months. None of the patient or tumor factors were found to have prognostic significance in univariate survival analysis. CONCLUSIONS: This is a single center experience of advanced GIST patients where small intestine was found to be the commonest disease site with imatinib producing disease stabilization in more than half of patients. Even though the survival was comparable to published reports, the major limitation was lack of mutation analysis.

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.

BACKGROUND: For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. METHODS: In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12,894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. FINDINGS: Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79­1·02] during years 5­9 and 0·75 [0·62­0·90] in later years; breast cancer mortality RR 0·97 [0·79­1·18] during years 5­9 and 0·71 [0·58­0·88] in later years). The cumulative risk of recurrence during years 5­14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5­14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12,894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89­1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13­3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83­1·36), ischaemic heart disease 0·76 (0·60­0·95, p=0·02), and endometrial cancer 1·74 (1·30­2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5­14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). INTERPRETATION: For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. FUNDING: Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.

Autologous Stem Cell Transplantation in Adult Hodgkin Lymphoma at a Tertiary Care Center in India: Analysis of Outcomes and Prognostic Factors.

High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard of care treatment in relapsed/refractory Hodgkin lymphoma (rrHL). Published long-term follow-up data concerning this modality from the Indian subcontinent is lacking. In this retrospective study, the data on adults (> 16 years) with biopsy-confirmed rrHL who were autografted from 1 January 2000 to 31 December 2021 at our transplant unit were analyzed. Progression-free survival (PFS) was defined as time from transplant to disease progression or death due to any cause. Overall survival (OS) was determined from date of transplant to date of death due to any cause. Overall, 134 patients with Hodgkin lymphoma underwent ASCT. At a median follow-up of 38.2 (range, 0.1-240) months, 5 years PFS was 45.3% (95% CI 35.4-54.4). The probability of OS at 5 years was 60.5% (95% CI 49.6-69.6). Eleven (8.2%) patients suffered transplant-related mortality by 100 days. Post-transplant persistent disease, pre-transplant serum hypoalbuminemia (< 3.5 g/dl) and chemo-resistance (< PR after last salvage regimen) of tumour at transplant were independent prognostic factors associated with worse PFS in multivariable analysis. Likewise, age ≥ 30 years, ECOG performance status ≥ 1 and residual disease after transplantation correlated with inferior OS. Long-term outcomes of rrHL patients undergoing ASCT in India match those from the developed world in the era of peripheral blood stem cell transplantation. Pre-transplant performance status, chemo-sensitivity of disease, serum albumin and post-transplant remission status determined survival in our cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01690-x.

Superior vena cava syndrome and poor performance status at presentation affect survival in mediastinal T-lymphoblastic lymphoma--a single institute experience from India.

Analysis of mediastinal T-lymphoblastic lymphomas (T-LBL) with T-acute lymphoblastic leukemia has precluded identification of prognostic factors. Newly diagnosed T-LBL patients presenting with mediastinal mass and <20% bone marrow involvement were analyzed for clinical features and outcome. In 55 patients with median age 18 years, 39 (71%) had "B" symptoms, 46 (83.6%) had bulky mediastinal mass and two thirds of patients (n = 36) had superior vena cava syndrome/superior mediastinal syndrome (SVCS/SMS). With acute lymphoblastic leukemia (ALL)-like protocols in majority, complete remission was achieved in 58.2% patients. Estimated 5-year overall survival (OS) and event-free survival (EFS) were 59.8 and 51.6% (median follow-up-35 months). On multivariate analysis, poor Eastern Cooperative Oncology Group (ECOG) performance status (PS > 2; n = 14) affected OS (p = 0.007), while Poor ECOG PS and SVCS/SMS affected EFS (p = 0.008 and p = 0.035, respectively). Combination of baseline-poor PS and presence of SVCS/SMS predicted poor EFS in a prognostic model (HR 6.20; p = 0.002). This is the first outcome study from Asia which has been able to predict baseline ECOG PS and presence of SVCS/SMS as prognostic factors affecting EFS.

B cell non-Hodgkin's lymphoma: experience from a tertiary care cancer center.

Information on presentation and outcome of B cell non-Hodgkin's lymphoma (B-NHL) is limited from developing countries. Data of newly diagnosed adult aggressive B-NHL (n = 260) patients were analyzed for clinical presentation, histological subtype, response to therapy, and survival. Univariate and multivariate Cox-regression analyses were performed for identification of prognostic factors. Diffuse large B cell lymphoma was the most common subtype (71 %). Median age was 50 years (18-78 years). The most common symptom was peripheral lymphadenopathy seen in 66 % of cases. Forty-seven percent of patients had advanced stage (stage III/IV), and 41 % had ECOG performance status of II-IV. B symptoms and bulky disease were present in 47 and 26 %, respectively. Intermediate to high risk score according to the International Prognostic Index (IPI) was seen in 67 %. Cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) and CHOP-like regimens were used in 70 % cases, while R-CHOP was used in 18 % cases. For diffuse large B cell lymphoma (DLBCL) patients, in intent-to-treat analysis, the overall response and complete remission rates were 73 and 60 %, respectively. Four-year event-free and overall survival was 54 and 64.7 %, respectively. Presence of B symptoms (p = 0.004), stage III/IV (p = 0.02/p = 0.01), performance status II-IV (p = 0.001), serum albumin (<4 g/dl; p = 0.001), hemoglobin <10 g/dl (p = 0.001), high-risk IPI score (0.001), use of <6 chemotherapy cycles (p = 0.001), and failure to attain CR (p = 0.001) were significantly associated with lower event-free and overall survival. DLBCL is the most common B cell NHL seen at our center. Intermediate to high IPI was seen in 45 % and was associated with poor survival. Majority of the patients were treated without rituximab. In comparison to western data, we observed higher proportion of DLBCL, lower median age, higher male to female ratio, and higher proportion of patients with B symptoms in our study.

18F-FDG PET/CT in Bilateral Breasts Metastasis From Ovarian Carcinoma.

ABSTRACT: Ovarian carcinomas generally metastasize within the peritoneal cavity due to exfoliation of malignant cells from primary tumor. Metastasis to the breasts is an unusual event and may mimic primary neoplastic disease. Usually, breast metastasis presents as a single isolated, well-circumscribed soft tissue lesion, and serous papillary carcinoma is the most common type of ovarian tumor that can metastasize to the breast. Concurrent bilateral breast metastasis is rare event. We present a follow-up case of metastatic carcinoma ovary, demonstrating FDG-avid soft tissue density masses in the bilateral breast parenchyma along with bilateral axillary lymphadenopathy, biopsy of which revealed metastatic deposits from carcinoma ovary.

Long-Term Outcomes and Safety Trends of Autologous Stem-Cell Transplantation in Non-Hodgkin Lymphoma: A Report From A Tertiary Care Center in India.

PURPOSE: Published experience with autologous stem-cell transplantation (ASCT) in non-Hodgkin lymphoma (NHL) from the Indian subcontinent is extremely limited. Here, we describe the activity and outcomes of this treatment modality at a large tertiary care center in India. PATIENTS AND METHODS: We retrospectively analyzed adult patients with NHL who were eligible for ASCT and autografted between January 1, 2002, and December 15, 2020, at our transplant unit. Toxicities, complications, and long-term outcomes were compared between patients who underwent transplant during 2002-2012 (group A) and 2013-2020 (group B). RESULTS: Overall, 80 patients (group A, n = 37; group B, n = 43) underwent ASCT using peripheral blood stem cells. At a median follow-up of 57.6 months, the 5-year event-free survival (EFS) and overall survival (OS) were 43.5% and 47.6%, respectively, for all patients. More recently (group B), patients had reduced 100-day transplant-related mortality (2.3% v 21.6%, P < .01), improved 3-year EFS (52.9% v 37.3%, P = .04), and superior OS (at 3-year; 63.4% v 43.2%, P = .02). Patients in group B also tolerated the procedure better, with improved resource utilization. In multivariate analysis, an International Prognostic Index (IPI) ≥ 3 at diagnosis adversely affected EFS (hazard ratio [HR] = 2.82, P = .009) and OS (HR = 2.84, P = .01) after ASCT. Low pretransplant serum albumin levels were associated with inferior EFS (HR = 2.68, P = .02) and transplant-related mortality (odds ratio = 10.80, P = .02) after ASCT. CONCLUSION: It is feasible to achieve comparable short- and long-term outcomes in patients with NHL undergoing ASCT in a resource-poor country with improved supportive care and expertise of the transplant team and center.

Hodgkin's lymphoma--long-term outcome: an experience from a tertiary care cancer center in North India.

Limited information is available from developing countries on long-term outcome of patients with Hodgkin's lymphoma (HL). Between January 1998 and December 2005, 262 patients (age ≥15 years) underwent treatment. Patients' median age was 30 years, ranging from 15 to 72 years. Male to female ratio was 2.8:1. B symptoms were present in 64% of patients. Seventy percent of patients had stage III and IV disease. Mixed cellularity (52.3%) was the most common histology followed by nodular sclerosis (38%). ABVD chemotherapy was used in 85% of the patients, and 50% received radiotherapy as consolidation. Following treatment 92% of patients achieved complete response. Five-year freedom from treatment failure (FFTF) and overall survival rate are 78.3% and 86.6% ± 0.02% (95% CI 80.0-93.2%), respectively. Stage at presentation, number of lymph node regions involved (≥3 vs ≤2), presence of B symptoms, and serum albumin (≥40 vs <40 g/L) were important determinants of FFTF. In a subset analysis of stage I and II HL patients, presence of bulky disease and pure infradiaphragmatic disease was associated with inferior outcome. On multivariate analysis involvement of three or more number of lymph node regions was a significant predictor of inferior freedom from treatment failure survival (hazard ratio 2.2, p < 0.01). Our analysis confirms excellent outcome for patients of Hodgkin's lymphoma with results comparable to developed countries.

Therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy in patients of metastatic castrate resistant prostate cancer after taxane-based chemotherapy.

OBJECTIVES: 225Ac-PSMA-617 therapy has shown good response in many recent studies. We report our experience of targeted alpha therapy with 225Ac-PSMA-617 in mCRPC patients who have failed therapy with taxanes. MATERIALS AND METHODS: Thirty-eight patients with CRPC with progressive disease following at least one taxane-based chemotherapy received 225Ac-PSMA-617 between July 2017 and Nov 2019. Primary end point was a composite 50% PSA and radiological response. Secondary endpoints were PFS, OS, and changes in QOL. The differences in outcomes between patients with skeletal and lymph-node metastases versus those with visceral metastases were also studied. RESULTS: A composite response by predetermined criteria was observed in 25 (66%) of 38 patients. The median PFS was 8 months (95% CI 5.3-10.6 months). Median overall survival was 12 months (95% CI 9.1-14.9) with 16 patients alive at the time of censorship. There was no difference in response rates or survival statistics between patients with visceral metastases versus those with only bone and lymph-node metastases (Chi-square 1.51, df 1, Sig 0.218). The most common adverse effect was xerostomia. On the QOL Symptom score, Pain, Fatigue Insomnia, and constipation showed a significant improvement as compared to baseline. CONCLUSIONS: 225Ac-PSMA-617 is a safe and tolerable treatment option for mCRPC that demonstrates marked anti-tumour activity with improvement in quality of life even in patients of metastatic CRPC who have been previously treated with taxane-based chemotherapy.

Long-Term Survivors of Metastatic Colorectal Cancer: A Tertiary Care Centre Experience.

Background Prognosis of metastatic colorectal cancer (mCRC) is poor and goal of treatment is mainly palliative unless there is limited metastatic disease which is surgically resectable. Here, we report a case series of long-term survivors treated predominantly with chemotherapy. Methods This is a single-center retrospective analysis of patients of mCRC. Records of metastatic colorectal cancer patients registered at Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, between the year 2005 and 2015 were retrieved and reviewed. Inclusion criteria were patients who survived 5 years or more, treated mainly by chemotherapy, with either initial presentation as metastatic disease or those who progressed after initial surgery with or without adjuvant therapy. The details about the patient characteristics, treatment, and outcome were collected. The data were censored on September 30, 2020. Results Records of 370 mCRC patients were reviewed. Thirty-one patients with all the available details fulfilled the criteria for inclusion in the study. Median age was 53 years (range, 22-74 years). Sixteen were women (51.6%). Twenty-four (77%) were newly diagnosed cases with initial presentation as metastatic disease. Commonest site of primary was on the left (21, 67.6%) followed by right side and transverse colon in 5 patients each. Liver was the most common site of metastasis ( n = 18, 58.06%). In metastatic setting, the most common chemotherapy regimen used in the first line was CAPOX ( n = 11, 35.48%). Only three patients could undergo metastatectomy. Monoclonal antibodies could be used only in 14 patients. Median overall survival (OS) of this cohort is 81.6 months (95% confidence interval [CI], 69.73-117.9). Conclusion A small but significant proportion of mCRC patients may achieve and maintain durable responses and long term survival with use of combination of chemotherapy with or without biologics.

Expression of CD13/aminopeptidase N in precursor B-cell leukemia: role in growth regulation of B cells.

Expression of cell surface CD13 in acute B-cell leukemia (ALL-B) is often viewed, as an aberrant expression of a myeloid lineage marker. Here, we attempted to study the stage specific expression of CD13 on ALL-B blasts and understand its role in leukemogenesis as pertaining to stage of B-cell ontogeny. A total of 355 cases of different hematological malignancies were diagnosed by immunophenotyping. Among 68 cases of early B-cell ALL, 22 cases with distinct immunophenotype was identified as immature B-cell ALL. Blasts from these ALL-B patients demonstrated prominent expression of CD10, CD19, CD22, but neither cytoplasmic nor surface IgM receptors. This strongly indicates leukemogenesis at an early stage of B-cell development. We also identified, the existence of a subpopulation of cells with remarkably similar phenotype in non-leukemic marrow from healthy subjects (expressing CD10, CD19, CD22, CD24, Tdt together with the co-expression of CD13). This sub-population of B cells concomitantly expressing CD13 appeared to be a highly proliferating group. By blocking their cell surface CD13 in leukemic blasts with monoclonal antibody we were able to inhibit their proliferation. We hypothesized that neoplastic transformation at this stage may be facilitated by CD13. CD13 may thus be an important target for novel molecular therapy of early stage acute B-cell leukemia.

Detection and clinical relevance of BCR-ABL fusion gene in childhood T-lineage acute lymphoblastic leukemia: a report on 4 cases.

The bcr-abl rearrangement has rarely been reported in T-lineage acute lymphoblastic leukemia and the clinical significance of this translocation is currently unknown. We screened 28 children with T-lineage acute lymphoblastic leukemia at diagnosis by reverse transcription polymerase chain reaction for major and minor break point regions of bcr-abl fusion gene. Four out of 28 patients (14.2%) were bcr-abl positive for the minor breakpoint transcript. One of these patients was refractory to therapy, whereas the other 3 relapsed on therapy.

Successful pregnancy outcome with 5-flurouracil, epirubicin, cyclophosphamide chemotherapy, and hemostatic radiotherapy with abdominal shielding for metastatic invasive intraductal breast carcinoma.

A case of metastatic infiltrating breast cancer in a young multiparous lady with 33 weeks pregnancy is presented who was treated with combination chemotherapy and hemostatic radiotherapy and had successful pregnancy outcome.

Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences.

PURPOSE: The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS: This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS: Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)-based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION: This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.

Modified gemcitabine and oxaliplatin or gemcitabine + cisplatin in unresectable gallbladder cancer: Results of a phase III randomised controlled trial.

AIM: To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS). METHODS: Open label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2. SAMPLE SIZE: 108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%. TREATMENT: Modified gemcitabine and oxaliplatin (mGemOx)-gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)-gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks. RESULTS: Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval [CI]: 7·9-9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8-12·6) in mGemOx and 10·4 months (95% CI: 9·1-11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (-1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem. CONCLUSION: This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/001406.