Clinical, hematological and cytogenetic profile in fibroblast growth factor receptor 1 rearranged hematoloymphoid malignancies

The background of this study is FGFR1 belongs to a family of four, high-affinity receptor tyrosine kinase and is a legitimate oncogene associated with uterine, cervical, prostate, bladder, colorectal and lung cancers. It is rarely concomitant in myeloid and lymphoid neoplasms but has an aggressive clinical course with a high mortality rate when present. Cytogenetic abnormalities involving the FGFR1 gene is most frequently observed in AML, MPN with eosinophilia, T-ALL and T-LBL with ZMYM2 gene being the most common fusion partner. Methods of this study was to authors report a series of 4 cases with FGFR1 rearrangements. Results is three patients presented as T-cell Lymphoblastic lymphoma (T-LBL) and one as mixed phenotype acute leukemia (MPAL). The T-LBL cases harboured the FGFR1/ ZMYM2 fusion and the MPAL case harbored the CNTRL/FGFR1 fusion as identified by conventional cytogenetics and confirmed by molecular studies. Conclusion is authors herewith describe the clinical, biochemical, molecular and cytogenetic features observed in these cases

Experience with non-cremophor-based paclitaxel-gemcitabine regimen in advanced pancreatic cancer: Results from a single tertiary cancer centre

Background & objectives: Gemcitabine combined with non-cremophor-based paclitaxel is one of the standards of care in advanced inoperable pancreatic cancer. This study was undertaken to retrospectively evaluate real world non-trial outcomes with this combination. Methods: Patients with histologically proven advanced inoperable pancreatic adenocarcinoma (PDAC), treated with non-cremophor-based paclitaxel-gemcitabine combination (PG) (gemcitabine-nanoxel or gemcitabine-abraxane) between January 2012 and June 2015, were retrospectively analyzed. Response assessment was done every 8-12 wk with computed tomography scan and responses were measured as per the Response Evaluation Criteria in Solid Tumours 1.1 criteria where feasible. Toxicity was recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: A total of 78 patients with PDAC were treated with the combination. Of these, 83.3 per cent of patients had metastatic disease. The median number of chemotherapy cycles administered was three. The objective response rate for the whole group was 30.8 per cent. Grade III/IV toxicities were seen in 35.9 per cent of patients. Median PFS was 5.6 months and median OS was 11.6 months. Interpretation & conclusions: Non-cremophor-based paclitaxel in combination with gemcitabine appeared efficacious for advanced pancreatic cancers in routine clinical practice. Within the confines of a single-centre retrospective analysis, gemcitabine-nanoxel and gemcitabine-abraxane appeared to have similar efficacy and toxicity in advanced pancreatic cancers

A retrospective observational study to evaluate the reliability of staging and risk stratification of adolescent and adult patients with Hodgkin's lymphoma registered at the lymphoma clinic of a tertiary cancer center in Western India

Background: The treatment for Hodgkin's lymphoma is based on risk stratification of the disease, which is determined by staging, clinical, and laboratory parameters. The current staging systems are highly prone to error due to overlapping components and inter-observer variability. Objectives: We aimed to assess the reliability of staging and risk stratification performed by the clinicians at our busy multidisciplinary clinic. Materials and Methods: We conducted a retrospective analysis of 115 patients with newly diagnosed Hodgkin's lymphoma at the Tata Memorial Hospital, Mumbai, India, from 2016-2018. Patients who underwent baseline staging and risk stratification in the multidisciplinary lymphoma clinic were included in the analysis. The multidisciplinary lymphoma clinic is a collaboration between medical oncologists, radiation oncologists, nurses, social workers, and patient navigators. The staging and risk stratification performed during the multidisciplinary clinic were compared with those of a team of independent experts from medical oncology, radiation oncology, and nuclear medicine based on standard references (guidelines established by the German Hodgkin Study Group and the Ann Arbor Staging). Results: Discordance rates of 11.3% (n = 13) in disease staging and 7.8% (n = 9) in risk stratification were observed between the multidisciplinary clinic and the independent expert team. In all the discordant cases, there was up-staging of patients by the multidisciplinary clinic; all nine patients in early favorable risk category were misclassified as early unfavorable. The discordance rates were not significant, with a kappa score of 0.841 for staging and 0.855 for risk stratification. Conclusion: Misclassification of patients with Hodgkin's lymphoma based on the staging, and risk stratification may lead to over- or under-treatment. There is a need for a simpler, objective, and technology-driven risk stratification process

Dosimetric Impact of Voluntary Deep Inspiration Breath Hold (DIBH) in Mediastinal Hodgkin Lymphomas: A Comparative Evaluation of Three Different Intensity Modulated Radiation Therapy (IMRT) Delivery Methods Using Voluntary DIBH and Free Breathing Techniques

Hodgkin lymphomas are radiosensitive and curable tumors that often involve the mediastinum. However, the application of radiation therapy to the mediastinum is associated with late effects including cardiac and pulmonary toxicities and secondary cancers. The adoption of conformal IMRT and deep inspiration breath- hold (DIBH) can reduce the dose to healthy normal tissues (lungs, heart and breast). We compared the dosimetry of organs at risk (OARs) using different IMRT techniques for two breathing conditions, i.e., deep inspiration breath hold (DIBH) and free breathing. Twenty-three patients with early-stage mediastinal Hodgkin lymphomas were accrued in the prospective study. The patients were given treatment plans which utilized full arc volumetric modulated arc therapy (F-VMAT), Butterfly VMAT (B-VMAT), and fixed field IMRT (FF-IMRT) techniques for both DIBH and free breathing methods, respectively. All the plans were optimized to deliver 95% of the prescription dose which was 25.2 Gy to 95% of the PTV volume. The mean dose and standard error of the mean for each OAR, conformity index (CI), and homogeneity index (HI) for the target using the three planning techniques were calculated and compared using Student’s t-test for parametric data and Wilcoxon signed-rank test for non-parametric data. The HI and CI of the target was not compromised using the DIBH technique for mediastinal lymphomas. The mean values of CI and HI for both DIBH and FB were comparable. The mean heart doses were reduced by 2.1 Gy, 2.54 Gy, and 2.38 Gy in DIBH compared to FB for the F-VMAT, B-VMAT, and IMRT techniques, respectively. There was a significant reduction in V5Gy, V10Gy, and V15Gy to the heart (p p = 0.004). DIBH results in lower heart, lung, and breast doses than free breathing in mediastinal Hodgkin Lymphoma. Among the different IMRT techniques, FF-IMRT, B-VMAT, and F-VMAT showed similar PTV coverage, with similar conformity and homogeneity indices. However, the time taken for FF-IMRT was much longer than for the F-VMAT and B-VMAT techniques for both breathing methods. B-VMAT and F-VMAT emerged as the optimal planning techniques able to achieve the best target coverage and lower doses to the OARs, with less time required to deliver the prescribed dose

Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse mortality in alloHSCT. It is associated with an inflammatory immune response manifesting as cytokine storm with ensuing damage to target organs such as liver, gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) is known for its anti-inflammatory, immune-modulatory, and anticancer properties, which are appealing in the context of aGvHD. Herein, we demonstrated that prophylactic and therapeutic use of WSE in experimental model of alloHSCT mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD (hazard ratio [HR] = 0.15 [0.03-0.68], P ≤ .01), whereas 250 mg/kg was most effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P ≤ .01). WSE treatment protected liver, gut, and skin from damage by inhibiting cytokine storm and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not compromise the GvL effect, as alloHSCT with or without WSE did not allow the leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in vivo . WSE is currently under clinical investigation for the prevention and treatment of aGvHD

Retinopathy of prematurity care in peripheral districts in Odisha, India: Pilot for a sustainable model.

The outcome of a retinopathy of prematurity (ROP) program initiated in five districts of Odisha over 3 years with partnerships between the government and non-government organizations was prospectively analyzed. The mentoring partners trained the district ophthalmologists and neonatal care providers; the program was handed over when the trainees were considered competent enough to diagnose and treat babies with ROP. During the project period (July 2016-June 2019), 3058 babies were examined; ROP was detected in 33.81% (n = 1034) and 5.06% (n = 159) babies required treatment. At the end of the project, ROP screening was possible in all five districts, and treatment was possible in three districts. ROP care nodal centers were built in one government medical college. To strengthen the initial gain, we recommend creating an Odisha Retinopathy of Prematurity (OD-ROP) steering committee with private-public partnerships to support the program and monitor its progress in other districts of Odisha

ALK Positive Lung Cancer: Clinical Profile, Practice and Outcomes in a Developing Country

<div><p>Objectives</p><p>To evaluate the performance and treatment profile of advanced EML4—ALK positive Non-small cell lung cancer (NSCLC) patients in a developing country with potentially restricted access to Crizotinib.</p><p>Materials and Methods</p><p>A retrospective analysis of advanced ALK positive NSCLC patients who were treated from June 2012 to September 2015 was conducted. The primary goal was to evaluate outcomes of advanced ALK positive NSCLC in our practice and examine the logistic constraints in procuring Crizotinib.</p><p>Results</p><p>94 patients were available for analysis. 21 (22.3%) patients were started on Crizotinib upfront, 60 (63.8%) on chemotherapy, 10 (10.6%) on Tyrosine kinase inhibitors (in view of poor PS) and 3 (3.2%) patients were offered best supportive care. Reasons for not starting Crizotinib upfront included symptomatic patients needing early initiation of therapy (23.3%), ALK not tested upfront (23.3%) and financial constraints (21.9%). 69 patients (73.4%) received Crizotinib at some stage during treatment. Dose interruptions (> 1 week) with Crizotinib were seen in 20 patients (29%), with drug toxicity being the commonest reason (85%). Median Progression free survival (PFS) on first line therapy for the entire cohort was 10 months, with a significant difference between patients receiving Crizotinib and those who did not ever receive Crizotinib (10 months vs. 2 months, p = 0.028). Median Overall Survival (OS) was not reached for the entire cohort, with 1 year survival being 81.2%. Patients with an ECOG Performance Status (PS) of >2 had a significantly reduced PFS compared to patients with PS < = 2 (1.5 months vs. 11 months, p< 0.001). 47 patients with financial constraints (68.1%) received Crizotinib completely free via various extramural support schemes.</p><p>Conclusion</p><p>A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature.</p></div

sj-docx-1-cll-10.1177_09636897241226573 – Supplemental material for Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Supplemental material, sj-docx-1-cll-10.1177_09636897241226573 for Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect by Saurabh Kumar Gupta, Dievya Gohil, Mohd Bashar Momin, Subhash Yadav, Akanksha Chichra, Sachin Punatar, Anant Gokarn, Sumeet Mirgh, Nishant Jindal, Lingaraj Nayak, Lal Hingorani, Navin Khattry and Vikram Gota in Cell Transplantation</p