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BACKGROUND: We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). METHODS: This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. RESULTS: Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P < .001) and grade 2/3 neuropathy (17% vs 7%; P = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. CONCLUSION: FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation.CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944).
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Docetaxel , Junção Esofagogástrica , Fluoruracila , Leucovorina , Oxaliplatina , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Pessoa de Meia-Idade , Feminino , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Docetaxel/administração & dosagem , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Idoso , Receptor ErbB-2/genética , Oxaliplatina/administração & dosagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Estimativa de Kaplan-Meier , Compostos Organoplatínicos/administração & dosagem , Instabilidade de Microssatélites , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologiaRESUMO
Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT) has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who were in remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.
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Soumya Surath PandaGastric cancer (GC) is often ignored at a young age, which frequently leads to tragic consequences. The worldwide incidence of GC is increasing at a young age. In view of the limited Indian publication, we sought to characterize clinicopathological parameters and risk factors in the adolescents and young adults (AYA) population. Retrospective data from six centers (which are part of the Network of Oncology Clinical Trials in India) from 2015 to 2020 were collected from patient (18-39 years of age) records. This study was approved by the institutional ethical committee of individual centers. All statistical analyses were performed using Microsoft Excel and SPSS (Version 20). Data interpretation along with the analysis of obtained results was carried out using the following tests: Qualitative data was expressed in terms of frequency/percentage. One-hundred fifty-two AYA GC patients were enrolled. The 31 to 39 years age group was most affected in which 76.3% were females. The majority of patients were nonalcoholic (93.4%), nonsmokers (98.0%), and without a family history (98.0%). The most common (MC) presenting symptom was abdominal pain (67.1%). MC site was antrum (48%). Among esophagogastric junction cancers, the majority were type I and II Siewert classifications (77% [20/26] patients in cardia), MC histology-signet ring cell (67.1%) followed by diffuse-type (65.1%). Most were poorly differentiated (65.1%) and were diagnosed at an advanced stage (III & IV= 54.6%). This is one of our country's first large multicenter studies on GC in the AYA population. There was a higher female prevalence, aggressive tumor behavior and the majority of patients were diagnosed at a more advanced stage. The majority were nonsmokers with a negative family history. Awareness among general people, researchers, clinicians, and policymakers must be improved to better the loss of life years in the younger population.
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INTRODUCTION: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, owing to its aggressive nature and poor prognosis. The role of folate receptors, particularly folate receptor 1 (FOLR1) and folate receptor 2 (FOLR2), in cancer has been increasingly recognized due to their overexpression in various malignancies including gastric cancer, and its potential implications in cancer progression, treatment resistance and as therapeutic targets. OBJECTIVE: To evaluate the expression patterns of FOLR1 and FOLR2 in GC patients' tissue and blood specimens and to correlate these patterns with clinicopathological variables. METHODS: A total of 58 gastric cancer patients were enrolled at the Regional Cancer Centre (RCC) from March 2017 to March 2020. Immunohistochemical analysis was performed to examine the expression of FOLR1 and FOLR2 in formalin-fixed paraffin-embedded (FFPE) tissue samples. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze FOLR1 and FOLR2 expression in blood samples. Statistical analyses were conducted using chi-square tests, independent T-tests, and Kaplan-Meier survival analysis. RESULTS: FOLR1 and FOLR2 were overexpressed in 82.76% and 70.69% of gastric cancer tissues, respectively. High expression levels of FOLR1 were significantly associated with the diffuse type of gastric cancer (p<0.005). qRT-PCR showed significant overexpression of FOLR1 in gastric cancer blood samples compared to control samples, with a median fold change of approximately 14.18 times. Conversely, FOLR2 was significantly underexpressed in gastric cancer samples, with a fold change of 0.30. However, no significant correlation was found between FOLR2 expression and the clinicopathological features. The overall survival analysis did not show a significant difference in survival rates based on the expression levels of FOLR1 and FOLR2. CONCLUSIONS: This study highlights the differential expression patterns of FOLR1 and FOLR2 in gastric cancer and underscores the complexity of their roles in cancer biology. While FOLR1 shows potential as a biomarker for gastric cancer due to its overexpression, further studies are needed to fully elucidate the therapeutic and prognostic implications of folate receptors in gastric cancer.
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Background: Triple-negative breast cancer (TNBC) includes approximately 20% of all breast cancer and is characterized by its aggressive nature, high recurrence rates, and visceral metastasis. Pathological complete response (pCR) is an established surrogate endpoint for survival. The window of opportunity studies provide valuable information on the disease biology prior to definitive treatment. Objectives: To study the association of dynamic change in pathological, imagining, and genomic biomarkers that can prognosticate pCR. The study aims to develop a composite prognostic score. Design: Clinical, interventional, and prognostic biomarker study using the novel window of opportunity design. Methods: The study aims to enroll 80 treatment-naïve, pathologically confirmed TNBC patients, administering a single dose of paclitaxel and carboplatin during the window period before neoadjuvant chemotherapy (NACT). Tumor tissue will be obtained through a tru-cut biopsy, and positron emission tomography and computed tomography scans will be performed for each patient at two time points aiming to evaluate biomarker alterations. This will be followed by the administration of standard dose-dense NACT containing anthracyclines and taxanes, with the study culminating in surgery to assess pCR. Results: The study would develop a composite prognostic risk score derived from the dynamic change in the Ki-67, tumor-infiltrating lymphocytes, Standardized Uptake Value (SUV max), Standardized Uptake Value for lean body mass (SUL max), and gene expression level pre- and post-intervention during the window period prior to the start of definitive treatment. This outcome will aid in categorizing the disease biology into risk categories. Trial registration: The current study is approved by the Institutional Ethics Committee [Ethics: Protocol. no. JIP/IEC/2020/019]. This study was registered with ClinicalTrials.gov [CTRI Registration: CTRI/2022/06/043109]. Conclusion: The validated biomarker score will help to personalize NACT protocols in patients in TNBC planned for definitive treatment.
Precision in action: unveiling predictive biomarkers for enhanced TNBC treatment We are investigating new ways to predict how well a particular treatment will work in patients with a specific type of breast cancer called triple-negative breast cancer. The study goal is to find biomarkers that change in response to drugs to predict the complete elimination of cancer in patients before it spreads to other parts of the body. To do this, we are using a special research approach called a 'window of opportunity design.' This information could be valuable in personalizing and improving cancer treatments.
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Early-stage Hodgkin's lymphoma (ESHL) is highly curable, usually with a combination of chemotherapy and radiation. Real-world data may show differences in survival and prognostic factors when compared to clinical trials. There is limited published literature on ESHL from India. The data on the baseline characters, treatment, and outcomes of patients with ESHL (stage IA, IB, and IIA) were obtained from five institutions' medical records and entered in a common database. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan Meier method, and cox-regression analysis was used to identify prognostic factors. There were 258 patients [median age was 37 (18-75) years; [males:160 (62%); stage I: 41%; B symptoms: 17 (6%); bulky disease:19 (15%)] treated between 2000 and 2020 who were evaluable. The common chemotherapies used were ABVD [N = 180 (70%)], COPP-ABVD hybrid [N = 52 (21%)], and COPP [N = 14 (5%)]. Median number of cycles were 4 (2-8) and 93 (47%) received radiation at end of treatment. After a median follow-up of 60 months, the 5 years EFS was 87% and OS was 92%. On multivariate analysis, the following factors adversely affected the EFS: Male gender [hazard ratio (HR) = 2.23, P = 0.02] and Hemoglobin < 10.5g/dL [hazard ration (HR) = 2.20, P = 0.02], and the following adversely affected the OS: Hemoglobin < 10.5g/dL [hazard ratio (HR) = 4.05, P = 0.001], Male gender [hazard ratio (HR) = 3.59, P = 0.004], Stage 2 [hazard ratio (HR) = 2.65, P = 0.002] and ECOG PS (2-3) [hazard ratio (HR) = 3.35, P = 0.01]. Using the hemoglobin, stage and gender a 3-item prognostic score could identify patients with very good outcomes (score 0; 5 years OS:100%) and poor outcomes (score 3; 5 years OS; 49%). This is one of the first multi-center real-world data exclusively focusing on ESHL from India. Though the survival of the entire population was good, there are subsets of patients who have poor outcomes, which may be identified using simple parameters. These parameters need validation in a larger dataset. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01692-9.
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Context Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm. Recent studies have suggested that CD26-positive leukemic stem cells (LSCs) circulating in peripheral blood are specific for CML. Objective This study was undertaken to determine the proportion of CD26-positive LSCs at diagnosis and its change during tyrosine kinase inhibitor therapy. Design This prospective study was conducted on 43 cases of CML at diagnosis. For flow cytometry, peripheral blood cells were stained with CD45, CD34, CD38, CD3, and CD26. A sequential gating strategy with CD45/SSC (side scatter), CD34/SSC, and CD34/CD38 was applied to identify CD45+/34+/38- populations, from which CD26-positive stem cells were identified and compared with controls. Data analysis was done with Kaluza software. Results All patients diagnosed with CML were detected with CD26-positive LSCs. The median percentage of CD26-positive CML LSCs was 0.02 with a range of 0.001 to 1.77. None of the control samples showed CD26 positivity. The percentage and absolute count of CD26-positive CML LSCs were reduced after six months of tyrosine kinase therapy in patients with complete hematological remission. Conclusion Flow cytometric analysis of circulating CD26-positive CML LSCs is a non-invasive, rapid, and useful tool in the diagnosis and follow-up of CML.
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BACKGROUND: Multiple myeloma (MM), being the second most common hematological malignancy, has garnered significant attention. The ubiquitin proteasomal pathway (UPP), crucial for normal cell function, plays a pivotal role in myeloma pathophysiology, especially with the advent of bortezomib (BTZ). Dysregulation of the UPP has implications ranging from developmental abnormalities to cancer. OBJECTIVES: This study aimed to delineate the clinical characteristics of newly diagnosed multiple myeloma patients and investigate the influence of single nucleotide polymorphisms (SNPs) in NF-ĸB2 and TRAF3 genes on the risk and treatment response to bortezomib-based chemotherapy. MATERIALS AND METHODS: Conducted at JIPMER, Pondicherry, this prospective study enrolled 184 participants, comprising cases and controls. DNA extraction from peripheral blood samples was followed by SNP analysis through Real-time Polymerase Chain Reaction. Patients were categorized into Good and Poor responders, and SNP associations with treatment response, response rates, and survival outcomes were assessed using chi-square and Kaplan-Meier analyses. RESULTS: The median age of participants was 55 years, with backache being the most prevalent symptom (66.3%). Hypercalcemia (22%), renal failure (8.7%), and bone fractures (45.7%) were also observed, alongside high prevalence of anemia. Notably, the frequency of the TRAF3 rs12147254 A allele was lower in cases compared to controls (31% vs. 49%, P-value=0.002). Poor responders exhibited higher frequencies of the GA+AA genotypes in TRAF3 rs12147254 (OR-3.882(1.629-9.251), P-value-0.002) and NFKB2 rs1056890 (OR-3.308(1.366-8.012), P-value-0.008) when compared to good responders. The GA+AA genotype in TRAF3 rs11160707 SNP correlated with improved progression-free survival. CONCLUSION: The study findings underscore a significant association between genetic polymorphisms and treatment response outcomes, suggesting their utility in prognostic determinations and clinical outcomes prediction in multiple myeloma patients.
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Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/diagnóstico , Fator 3 Associado a Receptor de TNF/genética , Estudos Prospectivos , Polimorfismo de Nucleotídeo Único , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
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.
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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.
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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.
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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.
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Antieméticos , Antineoplásicos , Doenças Ósseas Metabólicas , Neoplasias da Mama , Osteoporose Pós-Menopausa , Humanos , Feminino , Pessoa de Meia-Idade , Peptídeos , Pós-Menopausa , Neoplasias da Mama/tratamento farmacológico , Remodelação Óssea , Biomarcadores , Densidade Óssea , Colágeno Tipo I , Pró-Colágeno , Vitamina D , Vértebras Lombares , Vitaminas , Antineoplásicos/efeitos adversos , DexametasonaRESUMO
INTRODUCTION: Understanding patients' self-reported chemotherapy side effects is significant because it affects patients' quality of life (QOL) and compliance with treatment. Our current knowledge of chemotherapy side effects comes from available literature, whose external validity is questionable. Moreover, there are very few studies available in the literature that focus on various cancers and their associated side effects. METHODS: A single-center, prospective observational study was conducted at a tertiary care center from July 2019 to July 2021. After deriving the sample size, we interviewed 76 consecutive study patients with gastric, periampullary, colorectal, and breast cancer for six months after chemotherapy initiation with a structured patient-reported outcome tool adapted in English and Tamil to record the side effects like diarrhea, vomiting, chest pain, constipation, dyspnea, fatigue, mucositis, and rash. The grading of symptoms was done according to the Common Terminology Criteria for Adverse Events version 5.0. The frequency and prevalence of side effects were calculated as the number of patients who reported the side effect of any grade at least once during the follow-up period. The incidence rate of side effects was calculated in terms of person-time. The association between each side effect and cancer type was calculated using the chi-square test and Fisher's exact test as appropriate. RESULTS: Of the 77 patients in the study, 51.9% were male, 63.6% were between 40 and 60 years of age, 45.5% had stage-3 disease, and 44.2% received neoadjuvant treatment. During the six-month follow-up period, 97.4% of patients experienced at least one side effect. Fatigue was the most common side effect (87%), followed by loss of appetite (71.4%) and diarrhea (49.4%). Approximately 66.7% of patients experienced six or more side effects. There was a statistically significant difference in the frequency of side effects between cancer types. However, age, socioeconomic status, BMI, comorbidity, chemo-intent, and stage of disease did not affect the frequency of side effects. CONCLUSIONS: This study highlights the need to integrate patient-reported side effects into routine clinical practice. Identifying these side effects, even if they are mild in intensity, and managing them in a timely manner may improve the patient's emotional state, QOL, and compliance with chemotherapy.
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Glioma is the most devastating high-grade tumor of the central nervous system, with dismal prognosis. Existing treatment modality does not provide substantial benefit to patients and demands novel strategies. One of the first-line treatments for glioma, temozolomide, provides marginal benefit to glioma patients. Repurposing of existing non-cancer drugs to treat oncology patients is gaining momentum in recent years. In this study, we investigated the therapeutic benefits of combining three repurposed drugs, namely, metformin (anti-diabetic) and epigallocatechin gallate (green tea-derived antioxidant) together with temozolomide in a glioma-induced xenograft rat model. Our triple-drug combination therapy significantly inhibited tumor growth in vivo and increased the survival rate (50%) of rats when compared with individual or dual treatments. Molecular and cellular analyses revealed that our triple-drug cocktail treatment inhibited glioma tumor growth in rat model through ROS-mediated inactivation of PI3K/AKT/mTOR pathway, arrest of the cell cycle at G1 phase and induction of molecular mechanisms of caspases-dependent apoptosis.In addition, the docking analysis and quantum mechanics studies performed here hypothesize that the effect of triple-drug combination could have been attributed by their difference in molecular interactions, that maybe due to varying electrostatic potential. Thus, repurposing metformin and epigallocatechin gallate and concurrent administration with temozolomide would serve as a prospective therapy in glioma patients.
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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.
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Neoplasias da Mama , Fraturas por Osteoporose , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Densidade Óssea , Estudos Prospectivos , Pós-Menopausa , Absorciometria de Fóton , Fraturas por Osteoporose/epidemiologia , Medição de Risco , Fatores de RiscoRESUMO
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.
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Plaquetas , Leucemia Mieloide Aguda , Humanos , Quimioterapia de Indução , Transfusão de Plaquetas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/etiologiaRESUMO
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.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Transplante AutólogoRESUMO
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.
Assuntos
Anorexia , Neoplasias Pulmonares , Adulto , Humanos , Pessoa de Meia-Idade , Olanzapina/uso terapêutico , Anorexia/induzido quimicamente , Anorexia/tratamento farmacológico , Anorexia/complicações , Qualidade de Vida , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/complicações , Método Duplo-Cego , Aumento de PesoRESUMO
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.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Capecitabina , Fosfatidilinositol 3-Quinases , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêuticoRESUMO
[This corrects the article DOI: 10.3389/fphar.2023.1096614.].