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BACKGROUND: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). MATERIALS AND METHODS: This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. RESULTS: Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n â= â6951; 30.1%) followed by Klebsiella pneumoniae (n â= â5801; 25.1%) and Pseudomonas aeroginosa (n â= â3041; 13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. CONCLUSION: This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.
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Programas de Optimización del Uso de los Antimicrobianos , Infección Hospitalaria , Humanos , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/etiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Escherichia coli , Estudios Retrospectivos , Farmacorresistencia Bacteriana , Control de InfeccionesRESUMEN
BACKGROUND: Advanced gastric cancer is associated with poor survival despite chemotherapy. Maintenance chemotherapy has been successfully tried in lung cancer and colorectal cancers however there is scarce literature on maintenance therapy in advanced gastric cancer. We report a prospective non-randomized single-arm trial of capecitabine maintenance after response to docetaxel, cisplatin, and 5-Flurouracil-based chemotherapy. METHODS: 50 patients with advanced gastric cancer, who had achieved response or had stable disease after 6 cycles of Docetaxel, Cisplatin, and 5-Flurouracil (D 75 mg/m2, C 75 mg/m2, FU 750 mg/m2/d d1-d5, q3 weeks) chemotherapy were prospectively selected to receive maintenance chemotherapy with capecitabine (1000mg/ m2 bid d1-d14 q21 days) until progression. RESULTS: During the median follow-up period of 18 months all patients had progressed, however, there was no treatment-related death, the median time to tumor progression was 10.3 months, with grade 3 and 4 toxicities in 10-15% of patients, and treatment delays in 75% of patients. CONCLUSIONS: Our study has shown that maintenance chemotherapy with capecitabine post-first-line docetaxel, cisplatin, and 5-FU-based chemotherapy is effective and delays tumor progression. However, toxicity was a concern in our study which led to treatment-related delays but without any treatment-related death. Most patients continued therapy till progression.
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Carcinoma , Neoplasias Gástricas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Carcinoma/tratamiento farmacológico , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Fluorouracilo/uso terapéutico , Estudios ProspectivosRESUMEN
The aim of this study was to evaluate the outcome of patients with soft tissue sarcoma of the extremity and abdominal wall. This is the retrospective analysis of patients from a prospectively maintained data base from a single institute. We identified 79 patients with intermediate- to high-grade soft tissue sarcomas who were treated at our institute between Jan 2015 and July 2018. Low-grade tumors were excluded. There were 60 males and 19 females with a mean age of 44.6 years. Of the 79 sarcomas, 50 were in the lower limb and 24 in the upper limb and 5 were in abdominal wall. The commonest subtypes were undifferentiated pleomorphic sarcoma (n = 21) and synovial sarcoma (n = 19). Only 9 patients had metastatic disease at presentation. All 79 patients underwent surgical resection with an intent to achieve clear margins. Amputation was done in 19 patients while wide excision of the tumor was done in 60 patients. Adjuvant radiotherapy was given in 49 patients while adjuvant chemotherapy was given in 35 patients. At last follow-up (73 patients), 48 patients are alive without disease, 9 are alive with disease, 12 patients had died of disease, and 4 patients died due to other causes. Overall survival (OS) for 3 year is 77.6%, and estimated mean survival is 55.05 months. Relapse-free surviva (RFS)l at 3 year is 74.3%, and estimated mean RFS is 51.78. The only independent factor that affected the OS was the dimension of primary tumor (p = 0.02). For disease-free survival, the independent factors that affected outcome were stage at presentation (p = 0.04) and dimension of the tumor (p = 0.04). Short-term results shown by this study shows good outcome in patient with intermediate- to high-grade sarcomas when multidisciplinary approach is utilized for the management. Patients who had metastatic disease at presentation did worse than patients who did not.
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Varun GoelBackground The purpose of this study was to study the effectiveness of gemcitabine and nab-paclitaxel combination as first-line chemotherapy regimen for the treatment of metastatic pancreatic cancer. There is scarcity of data regarding efficacy and toxicity profile of this combination in Indian population. Aims and Objectives The primary aim of this study was to assess efficacy of this regimen, for which evaluation done in terms of the objective response rate, progression-free survival (PFS), and overall survival. Safety data were also evaluated. Materials and Methods In this prospective study, gemcitabine plus nab-paclitaxel combination chemotherapy was given as first line in metastatic pancreatic carcinoma patients till progression or appearance of grade 3/4 toxicities with treatment. Results The study was performed in 30 patients comprising 18 (60%) males and 12 (40%) females. The median age was 60 years. Median number of cycles administered were six cycles per patient. Seventeen patients (56.67%) had a partial response and 0% had complete response. A total of seven (23.3%) patients progressed on chemotherapy and six (20%) had stable disease (SD). The disease control rate (responses and SD) was 76.7%. The median PFS was 5.75 months. There was no statistically significant difference in terms of response rates and baseline CA 19-9 levels. Most common toxicities were hematological toxicities with rates of grade 3/4 anemia and neutropenia of 20%. Among nonhematological toxicities, nausea (46.67%) and fatigue (30%) were the commonest. Conclusion Combination of gemcitabine and nab-paclitaxel is active and well tolerated in advanced pancreatic carcinoma. To the best of our knowledge, this is the first such study conducted in India.
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BACKGROUND: EGFR mutant NSCLC patients have leptomeningeal (LM) involvement in more than 9% cases. MATERIAL & METHODS: We conducted a study evaluating the diagnostic utility of cfDNA EGFR testing in CSF using DdPCR while comparing it against MRI and CSF cytology. We also looked for known EGFR mutations in the CSF sample. These mutations were also tested in paired plasma samples. We further compared which constituent of CSF (pellet/supernatant) had better yield. RESULTS: 21 patients comprised the study. Of these 17 patients were diagnosed to have LM involvement based on conventional criteria. All modalities had 100 % specificity and positive predictive value. However, MRI and CSF cytology had a poor negative predictive value. cfDNA had the highest sensitivity (92.3 %), negative predictive value (75 %), accuracy (94.1 %), and net comparative benefit. Paired plasma samples were available for 19 patients. Primary EGFR mutation was detectable in the CSF sample in 16/19 patients; however, the plasma sample was positive only in 7/19 patients. 3 samples were negative for primary EGFR mutation in both CSF and plasma. None of the CSF samples showed positivity for T790M mutation which could however be observed in two patients in plasma samples. Both supernatant and pellet were analysed for cfDNA mutation analysis in 18/21 patients. The intraclass correlation coefficient regarding the percentage fraction tumor-derived DNA of cfDNA observed was 0.83(95 % CI 0.29 to 0.95) between both samples. CONCLUSION: EGFR detection in CSF has a potential role in diagnosing LM involvement. T790 M resistance mutations are uncommon in CSF post first and second-generation TKIs. Both supernatant and pellet samples can be used for the extraction of cell-free DNA in CSF.
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Carcinoma de Pulmón de Células no Pequeñas , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas QuinasasRESUMEN
Ex vivo human tumor models have emerged as promising, yet complex tools to study cancer immunotherapy response dynamics. Here, we present a strategy that integrates empirical data from an ex vivo human system with computational models to interpret the response dynamics of a clinically prescribed PD-1 inhibitor, nivolumab, in head and neck squamous cell carcinoma (HNSCC) biopsies (N = 50). Using biological assays, we show that drug-induced variance stratifies samples by T helper type 1 (Th1)-related pathways. We then built a systems biology network and mathematical framework of local and global sensitivity analyses to simulate and estimate antitumor phenotypes, which implicate a dynamic role for the induction of Th1-related cytokines and T cell proliferation patterns. Together, we describe a multi-disciplinary strategy to analyze and interpret the response dynamics of PD-1 blockade using heterogeneous ex vivo data and in silico simulations, which could provide researchers a powerful toolset to interrogate immune checkpoint inhibitors.
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BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Genome-directed therapy is less toxic, prolongs survival and provides a better quality of life. Predictive biomarker testing, therefore, has become a standard of care in advanced lung cancers. The objective of this study was to relate clinical and pathological features, including response to targeted therapy (TT) and progression-free survival (PFS) with positive driver mutation. MATERIALS AND METHODS: Archival data of nonsmall cell carcinoma patients with Stage IV disease were retrieved. Those who tested positive for one of the four biomarkers (epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], MET, and ROS) were included. Patient demographics and clinical features were reviewed. Tumor histomorphology was correlated with oncological drivers. Treatment response, PFS, and overall survival were studied in three subcohorts of patients who received computed tomography (CT), CT followed by TT and those who received TT in the first line. RESULTS: A total of 900 patients underwent biomarker evaluation of which 288 tested positive. Frequency of the four biomarkers observed was 26.6% (229/860), 6.6% (51/775), 6.6% (5/75), and 5.1% (3/59) for EGFR, ALK, MET, and ROS-1, respectively. The median PFS for EGFR-mutated cohort was 12 months, whereas it was 21 months for ALK protein overexpressing cases. Patients treated with first-line tyrosine kinase inhibitors performed better compared to those who were switched from chemotherapy to TT or those who received chemotherapy alone (P < 0.05). CONCLUSION: Biomarker testing has improved patient outcome. Genome-directed therapy accords best PFS with an advantage of nearly 10 months over cytotoxic therapy.
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Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer. Patients with NSCLC are diagnosed at a locally advanced or metastatic stage where prognosis with palliative chemotherapy is poor. The discovery of epidermal growth factor receptor (EGFR) mutations has revolutionized cancer treatment for NSCLC by promoting the development of molecularly targeted therapies like tyrosine kinase inhibitors (TKIs). This review summarizes the clinical efficacy and tolerability of EGFR-TKIs, including osimertinib, in EGFR-mutated advanced NSCLC. EGFR-TKIs have demonstrated superior response and overall survival rates compared with chemotherapy in EGFR-mutated NSCLC. However, despite the initial rapid and durable clinical responses, acquired resistance to first- and second-generation TKIs eventually develops in most cases, with disease progression observed mostly within 12 months of treatment initiation. Osimertinib, a potent third-generation TKI, irreversibly inhibits mutated EGFR alleles, including T790M. In addition to longer survival and higher response rate, osimertinib has a favorable safety profile with a lower incidence of grade ≥3 treatment-related adverse events compared with other TKIs. Based on the efficacy and safety results, recently the National Comprehensive Cancer Network (NCCN) has included osimertinib as the "preferred first-line of treatment" in patients with metastatic EGFR mutationpositive NSCLC. Thus, osimertinib as first-line therapy for EGFRpositive patients irrespective of the T790M mutation status could be an ideal choice in the Indian setting where only 50% of patients opt for any second-line therapy after first-line failure.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , MasculinoRESUMEN
BACKGROUND: IHC and FISH are used for categorizing HER 2 status in breast cancer at the protein and DNA level, respectively. HER 2 expression at the RNA level is quantitative, cheaper, easier to standardize and free from interobserver variation. METHODS: 115 consecutive patients were tested by IHC, FISH and RT-PCR (test cohort). Assuming FISH result to be the response variable, ROC curves for RT-PCR ratio were analyzed to label HER 2 negative, equivocal and positive cases as RT-PCR score 1, 2 and 3, respectively. Inter-relationships between RT-PCR, IHC and FISH were defined. 'Clinical benefit' of a test was defined as proportion of patients labeled unequivocally as HER 2 positive or negative. Population for 1 year was simulated constraint to previous reports of HER 2 positivity and IHC category distribution by a meta-analysis of previous studies that evaluated concordance between IHC and FISH to determine HER 2 status (simulation cohort). Four diagnostic pathways in the simulation cohort were defined-(1) initial IHC, followed by FISH (conventional pathway); (2) initial RT-PCR, followed by FISH; (3) initial IHC, followed by RT-PCR and then by FISH; (4) initial RT-PCR, followed by IHC and then by FISH. The clinical benefit of IHC and RT-PCR in the four pathways was analyzed and sensitivity analysis for incremental cost-effectiveness ratio and cost-benefit comapring RT-PCR against IHC, both as first-line tests and among those with IHC score 2 as a reflex second-line test was performed by the Monte Carlo technique. FINDINGS: 115 patients comprised the study population. While none with IHC score of 0 or 1 was FISH positive for HER 2, all cases with IHC score of 3 were FISH positive. 43 cases were assigned IHC score of 2. Thus, 72 patients benefited from the initial IHC testing [clinical benefit 62.6%], with the overall concordance between IHC and FISH being 100% for those with IHC score of 0, 1 and 3 (conclusive IHC categories). For RT-PCR with 100% concordance, 15.7% (115-97 = 18) patients would have benefited from RT-PCR testing if it was used as a first-line test. If RT-PCR would have been used as a second-line test among those with IHC score 2 (n = 43), then only 6 patients would have been assigned a conclusive RT-PCR category (category 1 or 3) translating to a clinical benefit of 14% (6/43) as a second-line test. As a second-line test it had 51% probability to prove more cost-effective than the conventional pathway, provided the cost of RT-PCR was 0.4 times the cost of IHC. Also in a three-step pathway, RT-PCR upfront would have 56% probability of higher cost-benefit provided the cost of RT-PCR was 0.1 times the cost of IHC. CONCLUSION: RT-PCR results were found to be suboptimal to IHC in terms of discriminative ability and clinical benefit; thus, it is unlikely to replace IHC as a first-line test in the near future.
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Neoplasias de la Mama/genética , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Receptor ErbB-2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Sensibilidad y Especificidad , Fijación del Tejido/métodosRESUMEN
BACKGROUND: Recent advances and understanding in the field of lung cancer and advent of newer treatments have shown a significant improvement in survival in the patients. The present study was conducted to analyze the clinical profile of nonsmall cell lung cancer (NSCLC) patients treated in a single unit at a tertiary cancer care center. MATERIALS AND METHODS: In this retrospective analysis, 322 consecutive NSCLC patients from the year 2011 to 2012 treated in a single unit were included in the study. Patients with proven NSCLC were included in the study. The details of the patients included the demographic profile, pathological diagnosis as well as imaging data, tumor profile, details of treatment, and follow-up information. RESULTS: The majority of the patients (95.6%) were in the age group >40 years. A large group of the patients (57.1%) were present/reformed smokers. The major histological type was adenocarcinoma (60.9%), of which 22.8% patients were found to be epidermal growth factor receptor positive. Anaplastic lymphoma kinase rearrangement positivity rate was 4.8%. Furthermore, 68% patients had Stage 4 disease. Upfront palliative chemotherapy (CT) was offered in 61.8% patients and pemetrexed with platinum compounds was the main CT regimen (46.6%). Partial response was achieved in 45.7% patients, whereas stable disease was observed in 10.9% cases. Median progression-free survival was 5 months and overall survival was 55% at 36 months. CONCLUSION: NSCLC forms the largest subgroup of lung cancer with the patients presenting with advanced stages of disease. This area needs to be explored for the early detection and subsequently the radical treatment of the patients. Personalized approach may be considered for the management of lung cancer by identifying new predictive and prognostic biomarkers of this disease.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pemetrexed/administración & dosificación , Pemetrexed/efectos adversos , Platino (Metal)/administración & dosificación , Platino (Metal)/efectos adversos , Medicina de Precisión , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
OBJECTIVE: Levels of proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines play a key role in the progression of inflammation as well as cancer disease. We were investigating the potential association of single-nucleotide polymorphisms (SNPs)/haplotypes in proinflammatory (TNF A) and anti-inflammatory (IL-10) cytokines locus with the development of PCa in Indian population. MATERIALS AND METHODS: We had genotyped 235 BPH/PCa samples (130 BPH and 105 cancer) along with 115 control samples for proinflammatory (TNF A -238G/A and -308G/A) and anti-inflammatory (IL-10 -1082A/G, -819C/T and -592C/A) cytokines SNPs in the gene promoter region using ARMS-PCR method. RESULTS: Allelic frequencies of TNF A and IL-10 SNPs were found to be significantly associated with the risk of prostate cancer and BPH when compared to controls (p = 0.05). Further haplotypic analysis showed that two haplotypes of TNF A (AG and AA) and IL-10 gene (CCG and CTG) were serving as risk haplotypes for prostate cancer development. IL-10 risk haplotypes were found to be positively associated with aggressiveness of prostate cancer. We also noticed successively increasing percentage of TNF A and IL-10 risk haplotypes with life style habits like smoking (10 and 26%) and alcohol consuming (9 and 27%). CONCLUSIONS: According to our data, TNF A -238G>A and IL-10 -1082A>G, -819C>T and -592C>A may be associated with the development of prostate cancer and BPH. We could also notice higher frequency of TNF A and IL-10 risk haplotypes in smoker and alcohol user. Interestingly, IL-10 risk haplotype was positively associated with aggressiveness of tumor. This information can be used for the early diagnosis of disease and to improve tissue-specific treatment's efficacy which will be moving ultimately towards the discovery of personalized therapy.
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Interleucina-10/genética , Hiperplasia Prostática/genética , Neoplasias de la Próstata/genética , Factor de Necrosis Tumoral alfa/genética , Anciano , Consumo de Bebidas Alcohólicas/genética , Progresión de la Enfermedad , Haplotipos , Humanos , India , Estilo de Vida , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Factores de Riesgo , Fumar/genética , Población BlancaRESUMEN
More than 50% of non-small cell lung cancer (NSCLC) cases harbor an actionable mutation, and molecular testing at different intervals can help in personalized and targeted treatment. Core tissue biopsy and needle biopsy done at the time of diagnosis/disease progression are interventional, time-consuming and can affect the patients adversely. Noninterventional biomarker testing by liquid biopsy promises to revolutionize advanced stage cancer screening. The present report was formulated based on an expert panel meeting of renowned oncologists who gave their opinions for minimally invasive liquid biopsy to detect targetable molecular biomarkers in advanced NSCLC cases. An exhaustive literature search was done to support their recommendations. Clinical utility of minimally invasive liquid biopsy, for detection of molecular biomarkers in advanced stage NSCLC patients, was broadly discussed by the key opinion leaders.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Biopsia Líquida , Carcinoma de Pulmón de Células no Pequeñas/patología , Detección Precoz del Cáncer , Humanos , Mutación , Estadificación de NeoplasiasRESUMEN
Tyrosine kinase inhibitors (TKIs) are a pharmaceutical class of small molecules, orally available with manageable safety profile, approved worldwide for the treatment of several neoplasms, including lung, breast, kidney and pancreatic cancer as well as gastro-intestinal stromal tumours and chronic myeloid leukaemia. In recent years, management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) in patients with mutations in the epidermal growth factor receptor (EGFR). The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to these tyrosine kinase inhibitors (TKIs). Gastrointestinal (GI) adverse events (AEs) are frequently observed in patients receiving EGFR tyrosine kinase inhibitor therapy and are most impactful on the patient's quality of life. Dermatologic side effects are also relatively common among patients treated with EGFR inhibitors. Evidence has emerged in recent years to suggest that the incidence and severity of rash, positively correlated with response to treatment.These skin disorders are generally mild or moderate in severity and can be managed by appropriate interventions or by reducing or interrupting the dose. Appropriate and timely management make it possible to continue a patient's quality of life and maintain compliance; however if these adverse events (AEs) are not managed appropriately, and become more severe, treatment cessation may be warranted compromising clinical outcome. Strategies to improve the assessment and management of TKI related skin AEs are therefore essential to ensure compliance with TKI therapy, thereby enabling patients to achieve optimal benefits. This article provides a consensus on practical recommendation for the prevention and management of diarrhoea and rash in Non-Small Cell Lung Cancer (NSCLC) patients receiving TKIs.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Diarrea/prevención & control , Exantema/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Diarrea/inducido químicamente , Receptores ErbB/antagonistas & inhibidores , Exantema/inducido químicamente , Humanos , Neoplasias Pulmonares/patología , Guías de Práctica Clínica como Asunto , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
OBJECTIVES: To examine the epidemiology of microbiologically documented bacterial infection and the resistance pattern, among cancer patients undergoing treatment at RGCIRC, Delhi. DESIGN AND SETTING: Retrospective observational study in which culture reports obtained over 1 year in 2013, were analyzed. RESULTS: 13329 cultures were obtained over 1 year in 2013 and were analyzed. 23.6 % samples showed positive culture with majority being gram negative isolates (67.9 %). E. coli was the commonest gram negative isolate (49.4%) followed by klebsella (29.7%) and Staph. aureus was the commonest gram positive isolate. There was high incidence of ESBL in blood and urine (87.2% & 88.5%) and BLBLI were also high (78% & 83.9%). Carbapenem resistance was comparatively low (10%) and colistin sensitivity was quiet high (> 95%). CONCLUSIONS: Prevalence of MRSA and VRE in our institute is very less, whereas prevalence of ESBLs and BLBLI isolates amongst gram negative infections is around 80%. Gram negative isolates had poor sensitivity to cephalosporins and fluoroquinolones.
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Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Neoplasias/epidemiología , Neoplasias/microbiología , Atención Terciaria de Salud/estadística & datos numéricos , Infecciones Bacterianas/sangre , Infecciones Bacterianas/orina , Farmacorresistencia Bacteriana , Humanos , India/epidemiología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Neoplasias/sangre , Neoplasias/orina , Prevalencia , Estudios Retrospectivos , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Enterococos Resistentes a la Vancomicina/aislamiento & purificaciónRESUMEN
BACKGROUND: In squamous cell carcinoma of the head and neck (SCCHN), epidermal growth factor receptor is expressed at very high levels. Hence, we have done this study to assess the response and tolerability of cetuximab and platinum-based chemotherapy in recurrent and metastatic (R/M) head and neck squamous cell cancer (HNSCC) in view of paucity of data from the Indian subcontinent. MATERIALS AND METHODS: In this prospective study, patients of R/M SCCHN were randomly enrolled from September 2012 to April 2015. Chemotherapy (cisplatin/carboplatin/5-fluorouracil) and cetuximab-based treatment were administered up to 6 cycles or unacceptable toxicity. The response rates (RRs), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: In total, fifty patients were enrolled. The median age was 51.0 years. A total of 255 cycles of treatment were administered (median = 6 cycles/patient). Four patients (8.0%) experienced complete response and 21 (42.0%) experienced partial response. Twenty-one patients (42.0%) had stable disease and four patients (8.0%) experienced progressive disease. The disease control rate was 92.0%. Median PFS was 5.3 months (95% confidence interval [CI]: 4.52-6.14 months). Median OS was 9.933 months (95% CI: 8.58-11.28 months). There was statistically significant correlation between overall response and Eastern Cooperative Oncology Group performance status (P = 0.014), site of tumor (P = 0.027), and histological grade of tumor (P = 0.001). The main Grade 3/4 side effects seen were hematological in 44 (88%) and gastrointestinal in 28 (56%) patients. CONCLUSIONS: The RR of cetuximab plus chemotherapy of> 45% and the promising PFS rates are strong arguments for clinically testing this combination and this treatment schedule further in R/M HNSCC.
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Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cetuximab/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
OBJECTIVE: It has been demonstrated in few trials that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer (OC). However, in view of high treatment-related toxicities, various modifications in treatment schedules have been tried. In this study, response and tolerability of IP paclitaxel on day 8 with IV paclitaxel on day 1 and IV cisplatin day 2 in carcinoma ovary were evaluated. PATIENTS AND METHODS: In this prospective observational study, from March 2013 to December 2015, the efficacy and tolerability of adjuvant IP/IV chemotherapy in optimally cytoreduced Stage III epithelial OC (EOC) patients were assessed. RESULTS: Totally, sixty patients were enrolled. The median age of patients was 53 years (32-67 years). Out of a total of 360 IP cycles, 316 cycles (88%) were completed. Forty-five patients (76%) received all the 6 cycles by IP route. Eight out of those 45 patients had one or more adjustment including delay or dose reduction. After median follow-up of 22 months, eight patients (14%) had local or systemic recurrence. Median progression-free survival not reached yet. Catheter block was seen in five cases. Two cases had needle displacement and extravasations of drug around the port chamber. Six patients had Grade 3 abdominal pain and cramp. Grade 3/4 leukopenia was experienced by thirty patients (50%), but febrile neutropenia occurred in only 6 (10%) patients. Renal complication present in 4 (7%) patients. CONCLUSIONS: In Indian patients, adjuvant chemotherapy with day 8 I/P paclitaxel in optimally cytoreduced EOC is associated with comparable survival outcomes, less side effects and high treatment completion rate relative to literature published from Western countries.
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Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Adyuvante/métodos , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Epitelial de Ovario , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Estimación de Kaplan-Meier , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios ProspectivosRESUMEN
Although preoperative chemoradiation has shown to improve surgical outcomes in both loco-regional control and long term survival; it has still not become the standard of care in many centers. There is reluctance in accepting preoperative chemoradiation primarily due to fear of increased perioperative morbidity/mortality or non-availability of infrastructure and expertise. We present a retrospective analysis of our results of radical esophagectomy after neoadjuvant chemoradiation. All patients who underwent Radical Esophagectomy from January 2009 to December 2013 by a single surgical team at our institute were included in the series (n = 118). Patients undergoing surgery after chemo-radiation (group A = 66) were compared with those under going upfront surgery (group B = 52) in terms of patient variables (age, sex, comorbidities, tumor location, staging, histology) and postoperative surgical outcomes and complications using Chi square test. Overall and disease free survival was analyzed using Kaplan Meir curve. There was no difference in duration of surgery, postoperative stay and overall morbidity and mortality in both groups. Although group A patients had more of advanced cases clinically, but histopathology showed complete pathological response (pCR) in nearly 40 % patients and negative nodes (pN0) in 62.5 % patients. OS and DFS showed a trend towards better survival with preoperative chemoradiation. We conclude that radical esophagectomy after preoperative chemoradiation is feasible and safe in developing countries. Moreover pathological complete response correlates well with improved survival. Randomized control trials may be required to further substantiate the results.
RESUMEN
CONTEXT: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies. AIMS: To determine the safety, dose-limiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD). SETTINGS AND DESIGN: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age. MATERIALS AND METHODS: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD). STATISTICAL ANALYSIS USED: All data summaries were descriptive. PK parameters were estimated using compartmental analysis. RESULTS: 25 patients (16 male, 9 female, 26-66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days. CONCLUSIONS: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.
Asunto(s)
Antineoplásicos/administración & dosificación , Glicina/análogos & derivados , Neoplasias/tratamiento farmacológico , Sulfonas/administración & dosificación , Adulto , Anciano , Antineoplásicos/farmacocinética , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Glicina/administración & dosificación , Glicina/farmacocinética , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/metabolismo , Neoplasias/patología , Pronóstico , Sulfonas/farmacocinética , Factores de Tiempo , Distribución TisularRESUMEN
BACKGROUND: Triple negative breast cancer (TNBC) is a recent concept and the burning topic of research today. Various studies have been reported in western literature on TNBCs or the similar group of basal like cancers, all highlighting the poor prognostic features of this molecular subtype in comparison to the other types of breast cancers. However extensive data from India is lacking. The aim of this study was to analyze the epidemiological and clinical profile of TNBcs at our institute. MATERIALS AND METHODS: Data on 171 patients of TNBCs registered at this hospital between 2005 and 2008 and followed up until December 2010 was collected and reviewed for epidemiological and clinical features. RESULTS: The median age at presentation was 49 years (22-75 years). Sixty eight patients (40%) had lump in the breast of less than 1 month duration. Fourteen (8%) were nulliparous and 10 (7%) patients had crossed the age of 30 years at first full-term pregnancy, 89 (52%) were pre or peri-menopausal at presentation. Only 8 (5%) patients had a family history of breast or ovarian cancer. One hundred and six (62%) patients were stage II, 26 (15%) stage III, 21 (12%) stage I and 18 (10%) stage IV at presentation. One hundred and twenty eight patients (75%) had early breast cancer eligible for surgery at presentation, 25 (15%) were locally advanced and received neoadjuvant chemotherapy (NACT) and 18 (10%) were found to be metastatic. Modified radical mastectomy was the preferred surgical option by most patients (76%) who underwent upfront surgery in our study. The pathological overall response rates (complete and partial response) after NACT was 75% with complete response rate of 25% and there were no relapses in the complete responders. The median follow-up was 30 months (9-70 months). One hundred and twenty two patients (71%) were alive at last follow-up, 34 (22%) had relapsed, 18 (11%) had died due to progressive disease. Thirty one patients (18%) were lost to follow-up. Most of the relapses were systemic and rarely preceded by local relapses. CONCLUSIONS: TNBCs are aggressive cancers with high rates of systemic relapses within the first 3 years of presentation. Longer follow-up of these patients is required for more mature data on these cancers.