Knowledge and attitude on childhood cancer survivorship among healthcare trainees: a multicentre study from India.

BACKGROUND: The proportion of childhood cancer survivors (CCS) in low/middle-income countries (LMICs) is rising. CCS often develop several physical and psycho-social long-term adverse effects, with unique healthcare needs. Primary healthcare providers (primary care physicians (PCPs)), especially in LMICs, are often not equipped to handle survivorship care. This study aimed to assess knowledge, and attitude among trainee healthcare providers concerning major issues of paediatric survivorship care. METHODS: A multi-centre, cross-sectional, questionnaire-based study was conducted among nursing and medical undergraduate students, and postgraduate medical residents across three tertiary-care teaching hospitals in India-All India Institute of Medical Sciences, New Delhi; Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry; and Maulana Azad Medical College, New Delhi. A questionnaire with total of 24 questions (14 knowledge-based and 10 attitude-based) was finalised after validation by expert review and piloting. The major domains covered in the questionnaire included knowledge and attitude regarding long-term adverse effects and psychosocial, employment-related issues faced by the survivors. It was administered to the study participants electronically. The knowledge-based questions had true/false responses (scored as 0 or 1 if incorrect or correct, respectively). Attitude-based questions were scored as 5-point Likert scale. RESULTS: Total 898 responses were collected (median age: 21 years, 64% (576/898) female). Among the respondents, 44% were undergraduate medical students, 42% were nursing students and 14% were postgraduate medical residents. The mean (SD) of knowledge score was 8.72 (2.04) (out of 14). On multivariable analysis, only discipline of training predicted knowledge scores regarding survivorship care. Postgraduate medical residents (9.08) as well as undergraduate medical students (8.85), had significantly higher mean knowledge scores than nursing students (8.47) (p=0.004).Two questions were answered incorrectly by the majority; children and siblings of CCS need additional genetic screening (79% incorrectly answered true), and CCS face intimacy issues in relation to normal sexual functioning (59% incorrectly answered false).Nearly half (48%) of respondents believed that their knowledge of cancer survivorship issues was inadequate. Majority of respondents (84%) suggested that oncologists should handle long-term survivorship care rather than PCPs. CONCLUSION: Trainee healthcare providers in India reported inadequate knowledge regarding survivorship care. Improving awareness by incorporating survivorship in teaching curriculum is imperative to equip future PCPs to provide survivorship care across the country.

Spatially Conserved Spiral Wave Activity During Human Atrial Fibrillation.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia in the world and increases the risk for stroke and morbidity. During atrial fibrillation, the electric activation fronts are no longer coherently propagating through the tissue and, instead, show rotational activity, consistent with spiral wave activation, focal activity, collision, or partial versions of these spatial patterns. An unexplained phenomenon is that although simulations of cardiac models abundantly demonstrate spiral waves, clinical recordings often show only intermittent spiral wave activity. METHODS: In silico data were generated using simulations in which spiral waves were continuously created and annihilated and in simulations in which a spiral wave was intermittently trapped at a heterogeneity. Clinically, spatio-temporal activation maps were constructed using 60 s recordings from a 64 electrode catheter within the atrium of N=34 patients (n=24 persistent atrial fibrillation). The location of clockwise and counterclockwise rotating spiral waves was quantified and all intervals during which these spiral waves were present were determined. For each interval, the angle of rotation as a function of time was computed and used to determine whether the spiral wave returned in step or changed phase at the start of each interval. RESULTS: In both simulations, spiral waves did not come back in phase and were out of step." In contrast, spiral waves returned in step in the majority (68%; P=0.05) of patients. Thus, the intermittently observed rotational activity in these patients is due to a temporally and spatially conserved spiral wave and not due to ones that are newly created at the onset of each interval. CONCLUSIONS: Intermittency of spiral wave activity represents conserved spiral wave activity of long, but interrupted duration or transient spiral activity, in the majority of patients. This finding could have important ramifications for identifying clinically important forms of atrial fibrillation and in guiding treatment.

Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

PURPOSE: Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. OBJECTIVES: The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. METHODS: In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. RESULTS: In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. CONCLUSION: In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study.

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Central nervous system involvement in multiple myeloma: Experience from a tertiary cancer center and review of literature.

BACKGROUND: Multiple myeloma (MM) results from clonal expansion of immunoglobulin secreting, heavy chain class-switched, terminally differentiated B-lymphocytes (plasma cells), resulting in radiologic or biochemical evidence of end-organ damage. Though neurological manifestations (peripheral neuropathies, spinal radiculopathies, cranial nerve palsies, and metabolic encephalopathies) can occur during the disease course, direct central nervous system (CNS) infiltration by malignant plasma cells (CNS-MM) is very rare (~1%) and has a dismal prognosis (survival of <6 months). METHODOLOGY: Clinico-laboratory profile and outcome of CNS-MM patients diagnosed and treated at a tertiary cancer care hospital were retrospectively analyzed. RESULTS: On scrutinizing 500 consecutive myeloma case records, 4 patients with CNS-MM were identified. All these patients were diagnosed during myeloma relapse, and all had deceased within 1 week and 12 months of developing CNS infiltration. Our experience with CNS-MM patients is similar to the experiences documented across major world literature. CONCLUSION: Our manuscript reinforces that CNS-MM should be considered in any myeloma patient presenting with unexplainable CNS manifestations. As there are no prospective studies to recommend optimal treatment strategies, CNS-MM still remains a dismal complication of myeloma.

Aggressive Histology and Extensive Metastasis Characteristic of Very Young Gastric Cancer (Less Than 30 Years): A Retrospective Clinical Audit.

Narendran KrishnamoorthiObjectives Gastric cancer (GC) is an aggressive disease and remains one of the most common causes of cancer-related mortality worldwide. Incidence of gastric cancer in young (GCY) varies between 2 and 8%. GCY faces unique challenges such as biological variation, diagnosis at an advanced stage, issues related to fertility preservation, and psychosocial considerations. This study aimed to find the differences in clinical characteristics and treatment outcomes of GCY compared to gastric cancer in older adults (GCO). Material and Methods This is a retrospective study from a tertiary care center. We screened records from 2015 to 2020, identified 33 records of GCY (less than 30 years), and compared the data with GCO (greater than 30 years) during 2015 and 2018. Results We identified 33 patients with GCY with a median age of 28 years (21-30) and a female to male ratio of 2:1. In GCY, 60% of patients presented with metastatic disease. Diffuse-type histology was more common in the GCY than in GCO (66.7% vs. 41.7%, p = 0.001). In patients with metastasis, multiple metastases were common in GCY compared to GCO (45% vs. 15%, p = 0.003). The median duration of follow-up for all patients was 27 (24-29) months. In GCY, the median OS was not reached for patients treated with curative intent, and it was 13 months for those treated with palliative intent. Conclusion The incidence of GCY in our study was like the western literature. Female patients with aggressive diffuse histology and multiple extensive metastases were characteristic of GCY. The survival outcomes were identical to GCO.

Clinicopathological features and survival outcomes for gastric adenocarcinoma: Real-world single-center data.

INTRODUCTION: Gastric cancer is the fifth most-common cancer and fourth common cause for cancer-related deaths globally. Surgery preceded or followed by chemotherapy or chemoradiotherapy is considered an optimal treatment for locally advanced gastric cancer. This study is a real-world data from a tertiary referral institute in southern India, in its experience with treating gastric adenocarcinoma over a period of four years with a minimum of two-year follow-up. METHODS: This was a retrospective analysis of data of patients with histologically proven gastric adenocarcinoma enrolled in the Department of Medical Oncology from 2015 to 2018. The demographic details, presentation, staging, treatment received and outcomes of patients with gastric adenocarcinoma were collected and analyzed in this study. RESULTS: Total 488 patients with gastric adenocarcinoma were included for the study. The stage-wise distribution of patients revealed early and locally advanced (45%) and metastatic (55%). The peritoneum and liver were the common sites of metastasis. The treatment distribution of these patients included perioperative chemotherapy followed by surgery (25 [5%]), surgery followed by adjuvant chemotherapy (65 [13%]), surgery alone (16 [3%]), perioperative chemotherapy alone (23 [4%]), palliative chemotherapy (274 [56%]) and supportive care (85 [17%]). The median overall survival for curative, palliative and supportive treatment was 23 (18-28), nine (7.6-10.4) and four (2.7-5.3) months, respectively. The two-year overall survival in the intention to treat population in the primary surgery (n = 81) and perioperative chemotherapy groups (n = 66) was 67.4% vs. 29.9% (p < 0.0001), respectively. CONCLUSION: This study highlights the advanced nature of the presentation of gastric cancer patients and the poor rate of treatment completion. The median survival rates in curative patients remain to be dismally poor. The treatment sequence in curable gastric cancer of surgery followed by adjuvant chemotherapy vs. perioperative chemotherapy followed by surgery needs to be explored in our country.

Segmenting computed tomograms for cardiac ablation using machine learning leveraged by domain knowledge encoding.

Background: Segmentation of computed tomography (CT) is important for many clinical procedures including personalized cardiac ablation for the management of cardiac arrhythmias. While segmentation can be automated by machine learning (ML), it is limited by the need for large, labeled training data that may be difficult to obtain. We set out to combine ML of cardiac CT with domain knowledge, which reduces the need for large training datasets by encoding cardiac geometry, which we then tested in independent datasets and in a prospective study of atrial fibrillation (AF) ablation. Methods: We mathematically represented atrial anatomy with simple geometric shapes and derived a model to parse cardiac structures in a small set of N = 6 digital hearts. The model, termed "virtual dissection," was used to train ML to segment cardiac CT in N = 20 patients, then tested in independent datasets and in a prospective study. Results: In independent test cohorts (N = 160) from 2 Institutions with different CT scanners, atrial structures were accurately segmented with Dice scores of 96.7% in internal (IQR: 95.3%-97.7%) and 93.5% in external (IQR: 91.9%-94.7%) test data, with good agreement with experts (r = 0.99; p < 0.0001). In a prospective study of 42 patients at ablation, this approach reduced segmentation time by 85% (2.3 ± 0.8 vs. 15.0 ± 6.9 min, p < 0.0001), yet provided similar Dice scores to experts (93.9% (IQR: 93.0%-94.6%) vs. 94.4% (IQR: 92.8%-95.7%), p = NS). Conclusions: Encoding cardiac geometry using mathematical models greatly accelerated training of ML to segment CT, reducing the need for large training sets while retaining accuracy in independent test data. Combining ML with domain knowledge may have broad applications.

Cost-effectiveness of response-adapted therapy (RAT) for advanced Hodgkin's Lymphoma compared with conventional treatment in India: a Markov-model based analysis.

Cost effectiveness analysis of interim positron emission tomography (PET-2, done after 2 cycles of chemotherapy) based response adaptive therapy (RAT) approaches in advanced Hodgkin lymphoma (aHL) are not available from an Indian perspective. We used a five-year decision analytics model to assess the cost-effectiveness of the two RAT approaches [(escalation (RAT-1) or de-escalation (RAT-2)] compared with standard care (SOC) in aHL (mean age:35 years). Modelling data was derived from secondary sources and sensitivity analyses were performed to assess the robustness of the model. Net monetary benefit (NMB) gained from RAT2 in Indian rupees (INR) (INR 2,26,896) was higher than the RAT1 (INR 1,83,138) when compared with SOC. Proportion achieving the complete response after initial treatment (CR1) was the key determining factor for the RAT1/2 dominance over SOC. Despite higher initial input costs, response-adapted therapy of aHL was cost-effective by minimizing the cost incurred and disutility experienced during relapse and salvage.

Despite higher initial costs, response-adapted therapy based on the interim PET scan after 2 cycles of chemotherapy was more cost-effective when compared to standard therapy with 6 cycles of ABVD in patients with advanced Hodgkin's lymphoma. Among the RAT approaches, de-escalation (RAT-2) had better cost-effectiveness than the escalation approach (RAT-1).

A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment. Group negotiation to fix prices, issuing of uniform contracts with standardized terms and conditions, and procurement by individual hospitals also reduce costs and improve quality without significant investment. The National Cancer Grid, a network of more than 250 cancer centres in India, piloted pooled procurement to improve negotiability of high-value oncology and supportive care medicines. A total of 40 drugs were included in this pilot. The pooled demand for the drugs from 23 centres was equivalent to 15.6 billion Indian rupees (197 million United States dollars (US$)) based on maximum retail prices. The process included technical and financial evaluation followed by contracts between individual centres and the selected vendors. Savings of 13.2 billion Indian Rupees (US$ 166.7million) were made compared to the maximum retail prices. The savings ranged from 23% to 99% (median: 82%) and were more with generics than innovator and newly patented medicines. This study reveals the advantages of group negotiation in pooled procurement for high-value medicines, an approach that can be applied to other health systems.

Lorsque les systèmes de santé reçoivent peu de fonds publics et que leurs processus d'achat sont décentralisés, le prix et la qualité des médicaments contre le cancer ont un impact direct sur l'accès aux traitements efficaces contre la maladie. Des facteurs tels que l'application de prix différenciés, les négociations en fonction des volumes ainsi que la confiance placée dans des génériques bon marché dont la qualité n'a pas été évaluée peuvent entraîner des décalages entre l'offre et la demande, d'énormes dépenses non remboursables pour les patients et de piètres résultats thérapeutiques. Bien que les acquisitions groupées de médicaments puissent contribuer à résoudre certains de ces problèmes, le suivi du processus d'achat requiert un engagement considérable au niveau administratif. Les négociations collectives en vue de fixer les tarifs, l'établissement de contrats types assortis de conditions générales standardisées, mais aussi les achats effectués par des hôpitaux en particulier peuvent également faire baisser les coûts et améliorer la qualité sans nécessiter d'importants investissements. Le National Cancer Grid, un réseau réunissant plus de 250 centres d'oncologie en Inde, a testé un dispositif d'achat groupé visant à assurer une meilleure négociabilité pour des médicaments et soins de soutien essentiels contre le cancer. Au total, 40 substances ont été prises en compte dans ce projet pilote. La demande groupée en médicaments émise par 23 centres équivalait à 15,6 milliards de roupies indiennes (197 millions de dollars américains) d'après le prix maximal de vente au détail. Ce processus prévoyait une évaluation technique et financière, puis des contrats entre chaque centre et les distributeurs sélectionnés. Des économies de 13,2 milliards de roupies indiennes (166,7 millions de dollars américains) ont pu être réalisées par rapport au prix maximal de vente au détail. Ces économies étaient comprises entre 23 et 99% (médiane: 82%) et concernaient davantage les médicaments génériques que les marques et les médicaments récemment brevetés. La présente étude révèle les avantages que représentent les négociations collectives lors des achats groupés de médicaments essentiels, une approche applicable à d'autres systèmes de santé.

En los sistemas sanitarios con escasa financiación pública y procesos de adquisición descentralizados, el sistema de fijación de precios y la calidad de los medicamentos contra el cáncer afectan directamente al acceso a una terapia eficaz contra dicha enfermedad. Factores como los diferentes sistemas de determinación de precios, la negociación en función del volumen y la dependencia de genéricos de bajo precio sin evaluación de su calidad pueden generar retrasos en la oferta y la demanda, elevados gastos para los pacientes y malos resultados en el tratamiento. Aunque la adquisición conjunta de medicamentos puede ayudar a abordar algunos de estos retos, el seguimiento del proceso de adquisición requiere una inversión administrativa considerable. La negociación colectiva a la hora de determinar los precios, la emisión de contratos unificados con términos y condiciones estandarizados y la adquisición por parte de algunos hospitales también reducen los costes y mejoran la calidad sin necesidad de realizar una gran inversión. La Red Nacional de Cáncer, una red que cuenta con más de 250 centros oncológicos en la India, puso a prueba la adquisición conjunta con el fin de mejorar la negociabilidad de medicamentos oncológicos y de tratamiento complementario que resultaban costosos. En esta prueba piloto se incluyó un total de 40 medicamentos. La demanda conjunta de medicamentos por parte de 23 centros fue equivalente a 15 600 millones de rupias indias (197 millones USD) según los precios minoristas máximos. El proceso incluyó una evaluación técnica y financiera, así como contratos entre centros independientes y proveedores seleccionados. Se logró un ahorro de 13 200 millones de rupias indias (166,7 millones USD) en comparación con los precios minoristas máximos. El ahorro osciló entre el 23 y el 99% (media: 82%) y fue más alto con los medicamentos genéricos que con los de marca y los recién patentados. Este estudio pone de manifiesto las ventajas de la negociación colectiva en lo que respecta a la adquisición conjunta de medicamentos costosos, un enfoque que se puede aplicar a otros sistemas sanitarios.

Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy.

INTRODUCTION: The burden and mechanisms of endocrine therapy-related bone loss are well known, while there are limited data on chemotherapy-induced bone resorption. The study aimed to evaluate the effect of cytotoxic chemotherapy on bone homeostasis among postmenopausal women with non-metastatic breast cancer. MATERIALS AND METHODS: Early and locally advanced postmenopausal non-metastatic breast cancer patients aged 45 to 65 planned for three cycles of anthracycline and four cycles of taxane chemotherapy administered along with dexamethasone (cumulative dose-256 mg) as an antiemetic from June 2018 to December 2021 were included. Bone mineral density (BMD), bone turnover markers, calciotropic hormones, pro-inflammatory cytokines, oxidative stress, and total antioxidant levels (TAS) were measured. RESULTS: We recruited 109 patients, with early 34 (31.2%) and locally advanced breast cancer 75 (68.8%) with median age 53 (45-65) years. There was a significant decrease in the % BMD at the lumbar spine, neck of the femur, and total hip post-chemotherapy. There was a significant increase in serum C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels post-chemotherapy. PINP/CTX ratio significantly decreased post-chemotherapy. Serum 25-OH vitamin D was significantly reduced with a compensatory increase in plasma iPTH levels. The change in CTX, PINP/CTX ratio, 25-OH vitamin D, iPTH, and oxidative stress index was more pronounced during anthracycline as taxane chemotherapy. There were no significant changes in pro-inflammatory cytokine levels. CONCLUSION: Chemotherapy and dexamethasone as antiemetic resulted in significant bone loss, as evidenced by bone turnover markers. Further studies are required to understand the mechanism of chemotherapy-induced bone loss and the need for bone-strengthening agents during chemotherapy.

Management of B-cell lineage acute lymphoblastic leukemia: expert opinion from an Indian panel via Delphi consensus method.

Introduction: Currently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes. Objective: To develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings. Methods: Modified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts from India constituted the panel. Clinically relevant questions belonging to three major domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (≥ 80%), moderate (60%-79%), and no consensus (< 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review. Results: Experts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin-Frankfurt-Münster (BFM)-based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia-based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy. Conclusion: This expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings.

Optimising platelet usage during the induction therapy of acute myeloid leukaemia: Impact of physician education.

INTRODUCTION: Platelet products are scarce and expensive resources to be used judiciously. However, inappropriate usage is common. Lack of physician awareness is an important issue. We implemented a physician education program (PEP) along with repeated WhatsApp reminders at our centre. We audited the platelet usage practise before and after the intervention. METHODS: Charts of patients with acute myeloid leukaemia (AML) treated between January 2020 and August 2020 was reviewed, and the mean platelet usage per patient per day was calculated. Physician education was implemented between September 2020 and December 2020 (2 PowerPoint lectures of 20 min each and weekly WhatsApp messages containing the guidelines). Data of patients treated between Jan 2021 and August 2021 was prospectively audited to understand platelet usage and the indications for transfusions. The British Committee for the Standards in Haematology (BCSH) platelet transfusion guidelines were used as the adjudication tool to evaluate compliance. The mean platelet usage per day per kg body weight of a patient before and after the PEP was compared using the t-test. RESULTS: Group A (before physician education) consisted of 22 patients, and group B (after physician education) consisted of 23 patients. The mean number of platelet transfusions for each patient in a day per kg body weight was 125.7 × 108 in group A whereas, after the PEP, it had reduced to 73.9 × 108 amounting to an absolute reduction of 51 × 108 (58.8%) from the baseline with a statistical significance of P = 0.001. After implementing the PEP, the mean number of random donor platelets used reduced by 10.25 units (34% reduction), and the mean single donor platelets used reduced by 0.83 units (19% reduction). The 190 requests for platelet transfusion received during this period were classified as appropriate (157/190), which constituted 82.63% of the requests, or inappropriate (33/190), which accounted for 17.36%. CONCLUSIONS: A short-duration education programme supplemented with weekly WhatsApp messages and an active feedback mechanism on the rationale of platelet transfusion by the treating physician and transfusion specialist could significantly reduce platelet consumption during the therapy of acute myeloid leukaemia patients. This is a measure that can be considered by all high-volume haematology centres, which can improve patient safety and reduce costs.

Quantifying a spectrum of clinical response in atrial tachyarrhythmias using spatiotemporal synchronization of electrograms.

AIMS: There is a clinical spectrum for atrial tachyarrhythmias wherein most patients with atrial tachycardia (AT) and some with atrial fibrillation (AF) respond to ablation, while others do not. It is undefined if this clinical spectrum has pathophysiological signatures. This study aims to test the hypothesis that the size of spatial regions showing repetitive synchronized electrogram (EGM) shapes over time reveals a spectrum from AT, to AF patients who respond acutely to ablation, to AF patients without acute response. METHODS AND RESULTS: We studied n = 160 patients (35% women, 65.0 ± 10.4 years) of whom (i) n = 75 had AF terminated by ablation propensity matched to (ii) n = 75 without AF termination and (iii) n = 10 with AT. All patients had mapping by 64-pole baskets to identify areas of repetitive activity (REACT) to correlate unipolar EGMs in shape over time. Synchronized regions (REACT) were largest in AT, smaller in AF termination, and smallest in non-termination cohorts (0.63 ± 0.15, 0.37 ± 0.22, and 0.22 ± 0.18, P < 0.001). Area under the curve for predicting AF termination in hold-out cohorts was 0.72 ± 0.03. Simulations showed that lower REACT represented greater variability in clinical EGM timing and shape. Unsupervised machine learning of REACT and extensive (50) clinical variables yielded four clusters of increasing risk for AF termination (P < 0.01, χ2), which were more predictive than clinical profiles alone (P < 0.001). CONCLUSION: The area of synchronized EGMs within the atrium reveals a spectrum of clinical response in atrial tachyarrhythmias. These fundamental EGM properties, which do not reflect any predetermined mechanism or mapping technology, predict outcome and offer a platform to compare mapping tools and mechanisms between AF patient groups.

Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer.

PURPOSE: Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy. METHODS: Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity. RESULTS: We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P < .001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal. CONCLUSION: Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Efficacy and safety of pomalidomide, bortezomib, and dexamethasone combination chemotherapy for newly diagnosed multiple myeloma: POMACE Phase II Study.

Bortezomib, lenalidomide, and dexamethasone induction chemotherapy (VRd), followed by autologous stem cell transplantation (ASCT), are the standard of care for patients with newly diagnosed multiple myeloma (NDMM). Pomalidomide is currently approved for relapsed-refractory multiple myeloma. This single-arm, open-label, phase 2 study was the prospective evaluation of the efficacy and safety of bortezomib, pomalidomide, and dexamethasone (VPd) induction for NDMM. We used Fleming's two-stage design for sample size calculation. We included transplant-eligible and ineligible patients aged 18-75 years in the study. The patients received four cycles of VPd induction followed by response assessment. Thirty-four patients were included in the study, of which 31 completed all four cycles of induction. The median age was 52 years (32-72). Thirty (91%) patients had multiple myeloma, and three had multiple plasmacytomas with less than 10% bone marrow involvement. Nine (27%) had ISS-I, 9 (27%) had ISS-II, and 15 (46%) had ISS-III myeloma. Three patients had high-risk cytogenetic abnormalities. After four cycles of VPd induction, ten patients (32%) achieved stringent CR, nine had CR (29%), eight (26%) had VGPR, and 4 (13%) had PR. Fifteen (48%) had a complete metabolic response (CMR) on PET-CT. Two patients developed SAEs. Anemia was the most common hematological toxicity. Peripheral neuropathy and constipation were the most common non-hematological toxicities. Patients with ≥VGPR had significantly better 12-month PFS than those with PR. Patients with ≥VGPR and CMR on PET-CT had significantly better 12-month OS. Our study showed VPd induction is safe and efficacious in NDMM. Further Phase 3 studies are necessary to establish the superiority and survival benefits.

Cytotoxic chemotherapy is associated with decreased bone mineral density in postmenopausal women with early and locally advanced breast cancer.

PURPOSE: The burden and mechanisms of endocrine therapy-related bone loss have been studied in detail. However, there is limited data regarding cytotoxic chemotherapy's impact on bone health. There are no definitive guidelines for bone mineral density (BMD) monitoring and treatment with bone-modifying agents during cytotoxic chemotherapy. The study's primary objective was to evaluate the changes in BMD and fracture risk assessment tool (FRAX) scores among breast cancer women on cytotoxic chemotherapy. METHODS: One hundred and nine newly diagnosed early and locally advanced postmenopausal breast cancer patients planned for anthracycline and taxane-based chemotherapy were recruited prospectively during the study period from July 2018 to December 2021. BMD of the lumbar spine, the femoral neck, and the total hip were assessed by dual-energy X-ray absorptiometry scan. BMD and FRAX scores were evaluated at baseline, end of chemotherapy, and 6 months of follow-up. RESULTS: The median age of the study population was 53 (45-65) years. Early and locally advanced breast cancers were seen in 34 (31.2%) and 75 (68.8%) patients, respectively. The duration of follow-up between two BMD measurements was 6 months. The percentage of decrease in BMD at the lumbar spine, femoral neck, and total hip were - 2.36 ± 2.90, - 2.63 ± 3.79, and - 2.08 ± 2.80, respectively (P-value = 0.0001). The median risk of major osteoporotic fracture (MOF) at 10 years (FRAX score) increased from 1.7 (1.4) to 2.7% (2.4) (P-value = 0.0001). CONCLUSION: This prospective study in postmenopausal breast cancer women shows a significant association of cytotoxic chemotherapy with the worsening of bone health in terms of BMD and FRAX score.

Comparison of Efficacy of Aspirin Plus EOX vs. EOX Alone in Patients with Locally Advanced and Metastatic Gastric Cancer: a Randomized Clinical Trial.

PURPOSE: The role of aspirin in cancer prevention has been well defined; the last decade revealed its therapeutic role with improved efficacy when aspirin was added to capecitabine in heavily pre-treated metastatic colorectal cancer. Aspirin affects tumour growth through the PI3K pathway, which regulates apoptosis and autophagy. The objective was to compare the efficacy of aspirin plus epirubicin, oxaliplatin, capecitabine (EOX) chemotherapy versus EOX alone in locally advanced and metastatic gastric cancer. METHODS: All patients with advanced gastric cancer reporting to the Department of Medical oncology between March 2017 and May 2019 were screened for study eligibility. They were randomly assigned to standard EOX with or without aspirin at a daily dose of 150 mg. Tumour measurements were assessed at baseline and after 3-4 cycles by an independent blinded radiologist according to RECIST criteria 1.1. Toxicity profiles were recorded as per CTCAE v 4.03. Per-protocol group was identified as 70 patients. The primary endpoint was overall response rates in the per-protocol group (defined as patients who received a minimum of 3 cycles and had an evaluable response after randomization). The secondary endpoints included toxicity analysis, progression-free survival, and overall survival. RESULTS: Ninety-five patients who fulfilled the study inclusion and exclusion criteria were randomized to group 1 EOX (50) or group 2 EOX plus aspirin (45). Seventy patients were included for the per-protocol analysis. The overall response rate in group 1 was 27% compared to group 2, which was 42%, P = 0.176. The median duration of follow was 29 (18.56-39.45) months. The median overall survival (n = 95) of group 1 versus group 2 was 11 (8.58-13.42) months and 10 (6.86-13.14) months, respectively, P = 0.90. There was no statistical significance in the overall survival per-protocol analysis (n = 70) between group one 12 (8.75-15.25) months versus group two 12 (6.21-17.79) months, P = 0.50. CONCLUSIONS: There was no improvement in the response rates, progression-free survival, and overall survival on adding aspirin to EOX chemotherapy in locally advanced and metastatic gastric cancer in an unselected population. A further role of PI3K mutation as a biomarker needs to be evaluated in this setting.