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The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long-term follow-up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression-free survival, respectively. A high rate (61%) of treatment with next-line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine-containing therapy, with no new safety concerns. © 2020 British Society for Haematology and John Wiley & Sons Ltd

Next generation sequencing studies in chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial [treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)]. Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation; the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%), and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02, P

BACKGROUND During the treatment of diffuse large B-cell lymphoma (DLBCL) patients, treatment-related toxicities are higher in the initial phase of treatment (First cycle effect). Toxicities can be tumor lysis syndrome, deterioration in performance status, febrile neutropenia, and rarely mortality. Prephase treatment before definitive chemotherapy is used in European countries to alleviate these toxicities. METHODS This was a non-randomized study carried out with the aim to evaluate the role of prephase treatment given prior to definitive chemotherapy in newly diagnosed DLBCL patients. Patients were divided into 2 cohorts "prephase cohort" and "non-prephase cohort." Prephase cohort received prephase treatment consisting of vincristine (1 mg) on -6th day and prednisolone 100 mg daily for 7 days (-6th day to day 0). Prephase treatment was followed by CHOP/R-CHOP chemotherapy on day 1. Non-prephase cohort received chemotherapy without prephase. Both groups were followed up for 30 days post-first cycle chemotherapy. RESULTS A total of 100 patients with DLBCL (50 in each cohort) were enrolled. There was a significant improvement in performance status of the patients who received prephase. A majority of 92% patients attained ECOG performance status of either 0 or 1 before starting chemotherapy in the prephase cohort. Febrile neutropenia was lower (16%) in the prephase cohort as compared with the non-prephase cohort (34%; P = .037). CONCLUSION Prephase treatment prior to definitive chemotherapy (CHOP ± Rituximab) improves the performance status and decreases first cycle effect in DLBCL patients.

Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic variability of HBV within and across different compartments in a host using Next Generation Sequencing. Despite all 40 patients being HBV seronegative, 68% showed evidence of occult HBV. Sequencing of these gene segments revealed inter-compartment viral variants in 26% of them, each with at least one non-synonymous mutation. Between compartments, core gene variants revealed Arg94Leu, Glu86Arg and Ser41Thr while X gene variants revealed Phe73Val, Ala44Val, Ser146Ala and Ser147Pro. In tumor compartments per se, several mis-sense mutations were detected, notably the classic T1762A/A1764G mutation in the basal core promoter. In addition, a virus surface antigen mis-sense mutation resulting in M125T was detected in all the samples and could account for surface antigen negativity and occult HBV status. It would be interesting to further explore if a temporal accumulation of viral variants within a favored niche, like patients’ lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.

The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45− (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial–mesenchymal transition (EMT) in CTCs for clinical association.

Primary Non-Hodgkin’s Lymphoma of Ovary is a rare cancer. There is limited data in Indian population. Hence we undertook this retrospective observational study at our center in Southern India. This study includes 5 consecutive cases diagnosed as Primary Non-Hodgkin’s Lymphoma of Ovary between January 2009 and December 2015. Primary Non-Hodgkin’s lymphoma (NHL) of the ovary is rare with an incidence in the literature of 0.5% of NHL and 1.5% of ovarian tumours. Diffuse large B-cell type accounts for about 20% of PONHL. We studied five cases of primary ovarian NHL. All cases were diffuse large B-cell lymphoma of ovary. The patients ranged in age from 41years to 59 years with median age of presentation 50 years. Pain abdomen was the most common symptom (3/5-60%). According to Ann Arbor stage- Advanced stage ( IVE) was seen in 3 patients ( 60 %) and the rest 2 patients (40% ) had stage IE. 4 patients had Eastern co-operative oncology group (ECOG) performance status -1 and 1 patient had ECOG PS -2. B symptoms were seen in 3 out of 5 patients (60 %). According to IPI, 3 patients (60%) were in low intermediate risk and 2 patients (40%) had low risk score. 1 case was positive for BCL-6, 1 case was positive for CD10, 3 cases were positive for BCL-2, and 4 cases were positive for CD 20 . Patients were treated by various combinations of surgery, chemotherapy, and radiotherapy. Overall survival ranged from 6 months to 41 months with median OS of 23 months.

Background: Lymphomas comprise around 5% of all head and neck neoplasms and is the second most common extra nodal non hodgkin’s lymphoma (NHL). However there is sporadic data on this entity from the subcontinent and hence we undertook this study. Methodology: This retrospective observational study was conducted at a tertiary care oncology center in India on diagnosed cases of NHL between January 2007 and December 2013. All patients were diagnosed based on histopathology and immunohistochemistry. Staging work up was done in all patients. Patients were considered as primary Head and Neck lymphomas if there was head and neck as the predominant site with or without regional lymph node involvement. Results: A total of 39 patients were studied. The age at presentation ranged from 29 to 78 years. The most common site of presentation was oral cavity (26%; n=10), followed by parotid and thyroid (18% each; n=7), eye (12%, n=5), maxilla (8%; n=3), paranasal sinuses (8%; n-=3) cheek (8%, n=3), and nasal cavity (2%, n=1). 41% (n=16) cases were in stage I, 43% (n=17) in stage II, 3% (n=1) in stage III, and 13% (n=5) were in stage IV. Most common histology was DLBCL (71%; n=28), followed by plasmablastic (10%; n=4), marginal zone (8%, n=3), mantle cell (3%; n=1), follicular lymphomas (5%; n=2), and NK/T cell lymphoma (3%; n=1). Most of the patients were of low risk (67%; n=26), followed by intermediate (23%; n=9), and high risk (10%; n=4). Patients were treated with anthracycline based chemotherapy +/- radiotherapy. In this study, stage I and stage II patients had a better prognosis and overall survival, median OS 28 months and 11 months, respectively. In stage III and IV, it was 7 and 3 months, respectively. According to site, the best median overall survival was seen with parotid (27 m), paranasal sinus (26m), and oral cavity (23 m), followed by thyroid (18 m) nasal cavity (17 m), maxilla (11 m), eye (8 m), and cheek (7 m). Conclusions: Head and neck lymphoma is probably the tip of the iceberg and is an undereported entity.

Adrenocortical carcinoma is a rare cancer, with an incidence in the literature of 0.5 to 2 cases per million population per year which has a poor prognosis..There is limited data in Indian population. Hence we undertook this retrospective observational study of adrenal cortical carcinoma at our center in Southern India. This study includes 5 consecutive cases diagnosed as adrenal cortical carcinoma between January 2009 and December 2015 was included.Read Complete Article at ijSciences: V5201603981 AND DOI: http://dx.doi.org/10.18483/ijSci.981

Background. Acute promyelocytic leukemia is characterized by t(15;17). This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA), a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

The primary mucinous adenocarcinoma of the bladder is an extremely rare urologic entity, which is less than 2% of all urinary bladder tumours and often presents in advanced stage. A 68-year old gentleman was diagnosed with a primary mucinous adenocarcinoma of the bladder from biopsy of anterior abdominal wall ulcer. Immunohistochemistry was done to rule out metastasis from colon and prostate and it confirmed the nature of the tumour. As the patient presented in advanced (stage IV), palliative intent chemotherapy with gemcitabine and cisplatin was administered, however he succumbed to the illness after one cycle of chemotherapy. The primary adenocarcinoma of urinary bladder creates a diagnostic dilemma, as it is difficult to differentiate metastatic adenocarcinoma of the colon and prostate. The immunohistochemistry has a leading role, aiding in diagnosis.

Non-small cell lung cancer ranks among the most lethal cancers worldwide. The rate of epidermal growth factor receptor (EGFR) mutations and echinoderm microtubuleassociated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene fusion is the most common in younger age, non-smoking Asian adenocarcinoma lung cancer patients. EGFR mutations and ALK gene rearrangements are known to be mutually exclusive and as mutual causes of resistance to EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs. However, rarely such co-alterations do co-exist in some clinical cases. Here we report a 62 year old male, heavy smoker with cough, hemoptysis and fatigue. Histopathological examination of bronchoscopic guided biopsy showed adenocarcinoma histology. Staging evaluation, he was found to have stage IV disease on positron emission tomography-computed tomography scan. The biopsy blocks tested positive for both EGFR mutation and ALK fusion. Patient was initiated on tablet Gefitinib 250 mg once daily. To the best of our knowledge, there has been no report of dual EGFR mutation and ALK fusion positivity from India.

Aim: Breast cancer in women younger than 35 years old is uncommon and only accounts for 2% of all breast cancers diagnosed in Western countries. However, there is paucity of data on breast cancer in women younger than 35 years old in India. The aim of this study was to assess clinicopathological parameters in these young breast cancer patients. Methods: This retrospective study summarized data on women younger than 35 years with breast cancer between August 2012 and July 2013 from tertiary cancer center in India. Results: Out of a total of 320 patients, 36 were younger than 35 years old in this period of time and the median age was 32 years. A breast lump was the most commonly presented symptom with an average symptom duration of four months. The median age of the first childbirth was 22 years. Most of the patients had a stage III disease (52%) followed by stage II (33%). All patients had invasive ductal carcinoma and 86% of patients had high-grade tumors. 51% of patients were lymphnode-positive, and lympho vascular emboli were present in 43% of cases. Estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) positivity occurred in 38.9% and 22.2% of patients, respectively and 50% of patients were triple negative. Conclusion: Breast cancer occurring in women younger than 35 years old constituted 11.3% of all breast cancer cases in Kidwai Memorial Institute of Oncology, India. They had high tumor grade with a larger size and an increased incidence of lympho vascular emboli, which lead to aggressive behaviors and poor prognosis. This study suggest that early onset of breast cancer must be considered as a diagnostic possibility in Indian patients presenting palpable masses in the mammary glands.