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BACKGROUND: The world health organization (WHO) classification of neuroendocrine neoplasms (NENs, i.e. neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs)) of the gastrointestinal system involves grading of these tumors by mitotic count (i.e. H and E mitotic index or Haematoxylin and Eosin mitotic index [HE-MI] and Mindbomb E3 ubiquitin protein ligase 1 labelling index (MIB1-LI) into Grade 1 (G1), Grade 2 (G2), or Grade 3 (G3). However, the assessment of HE-MI and MIB1-LI is hindered by several factors that contribute to discordance between these two grading methods. Clinical data demonstrate the dependency of prognosis on grade. OBJECTIVES: The objective of this study was to compare the grading of NENs of the hepatopancreatobiliary (HPB) system using Anti-phosphohistone H3 mitotic index (i.e. PHH3-MI), HE-MI and MIB1-LI. MATERIALS AND METHODS: In a cohort of 140 NENs selected from January 2011 to August 2019, the concordance and correlation between HE-MI, MIB1-LI and PHH3-MI grading methods were analysed using Cohen's weighted kappa (κ) statistics and Spearman's correlation (ρ), respectively. Receiver operating characteristic (ROC) curve and cut-off analyses were done to determine optimal PHH3-MI cut-off values to grade NENs. RESULTS: The rates of discordance between HE-MI vs. MIB1-LI, PHH3-MI vs. MIB1-LI and PHH3-MI vs. HE-MI were 52% (κ =0.416), 29% (κ =0.64) and 41% (κ =0.508), respectively. There was a significant correlation between the grading methods. PHH3-MI had good overall sensitivity and specificity at cut-offs 2 and 17 in distinguishing between G1 vs. G2, and G2 vs. G3 tumors, respectively. CONCLUSION: PHH3 immunolabeling allowed for quick and easy identification of mitotic figures (MF). It had the highest concordance with MIB1-LI. At cut-off values of 2 and 17, there was good overall sensitivity and specificity. The interobserver agreement was excellent.
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PURPOSE: We examined the efficacy of topical capsaicin in reducing delayed chemotherapy-induced nausea and vomiting (CINV). METHODS: Adults on highly emetogenic chemotherapy regimens applied 2 g of capsaicin ointment (0.075%) or matching placebo four times a day to the abdomen for 5 days in addition to standard antiemetic regimen in this blinded randomized controlled trial. Patients were monitored for nausea and vomiting in the immediate (day 1), delayed (days 2-5), and extended phases (days 2-15). Self-reported incidence and daily episodes of CINV were compared between the groups. Onset, severity, need for rescue antiemetics, cumulative vomiting episodes, and safety were also compared. RESULTS: In total, 160 patients were enrolled. The final modified intention-to-treat population included 75 patients each in the capsaicin and placebo groups. Fewer patients experienced nausea (36.0% [n = 27] v 53.3% [n = 40]; P = .033) and vomiting (28.0% [n = 21] v 42.7% [n = 32]; P = .060) in the capsaicin arm during the delayed phase. During the extended phase, there was a significantly lower incidence of nausea (44% v 64.0%; P = .014) in the capsaicin arm. No difference in nausea (26.7% v 25.3%) or vomiting (22.7% v 18.7%) was evident in the immediate phase. The average daily episodes of nausea and vomiting were significantly fewer in the capsaicin arm during the delayed and extended phases. With capsaicin, no grade 3 nausea (9.3% v 0.0%; P = .007) was observed, and the time to first nausea and vomiting was significantly prolonged. There were no differences between the groups with respect to rescue antiemetics, unscheduled hospital visits, and adverse events. CONCLUSION: Topical capsaicin reduced the incidence of nausea and the average number of vomiting episodes during delayed and extended phases without increasing adverse effects.
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Capsaicina , Náusea , Vômito , Humanos , Capsaicina/administração & dosagem , Capsaicina/efeitos adversos , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/epidemiologia , Náusea/induzido quimicamente , Náusea/prevenção & controle , Náusea/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Administração Tópica , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE(S): The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before the start of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT. METHODS: Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals. RESULTS: One hundred and fifty patients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66. CONCLUSION: Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies.
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Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]-83%-97%) and the overall survival (OS) rate was 90% (95% CI-80%-95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.
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Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers. We also aimed to identify population specific BRCA1/2 mutation hotspots, to enable the development of more affordable testing strategies. We identified 921 patients with breast and ovarian cancer who underwent mutation testing. The target enrichment was followed by targeted NGS in 772 patients and an allele-specific PCR (ASPCR) based genotyping for BRCA1:c.68_69delAG (or 185delAG), was carried out in 149 patients. We identified 188 (20.4%) patients with BRCA1/2 variants: 118 (62.8%) with pathogenic/likely pathogenic and 70 (37.2%) with VUS. The 185delAG was identified as a recurrent mutation in the Southern Indian population, accounting for 24.6% of the pathogenic variants. In addition, a family history of breast, ovary, pancreas, or prostate (BOPP) cancer was found to be associated with an increased risk of identifying a deleterious BRCA1/2 variant [OR = 2.11 (95% CI 1.45-3.07) p ≤ 0.001]. These results suggest that Targeted NGS is a sensitive and specific strategy for BRCA testing. For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies.
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Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor survival compared to other subtypes. Patients with residual disease after neoadjuvant chemotherapy (NAC) face an increased risk of relapse and death. We aimed to characterize the mutational landscape of this subset to offer insights into relapse pathogenesis and potential therapeutic targets. We retrospectively analyzed archived paired (pre- and post-NAC) tumor samples from 25 patients with TNBC with residual disease using a targeted 72-gene next-generation sequencing panel. Our findings revealed a stable mutational burden in both pre- and post-NAC samples, with a median count of 12 variants (IQR 7-17.25) per sample. TP53, PMS2, PTEN, ERBB2, and NOTCH1 variants were observed in pre-NAC samples predominantly. Notably, post-NAC samples exhibited a significant increase in AR gene mutations, suggesting potential prognostic and predictive implications. No difference in mutational burden was found between patients who did and did not receive platinum (p = 0.94), or between those with and without recurrence (p = 0.49). We employed K-means clustering to categorize the patients based on their variant profiles, aiding in the prediction of possible patterns associated with recurrence. Our study was limited by its small sample size and retrospective design, suggesting the need for further validation in larger prospective cohorts.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Estudos Retrospectivos , Terapia Neoadjuvante , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/genética , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Mutação , RecidivaRESUMO
Mansi AgrawalVidya KonduruBackground Oral cavity cancers require definitive surgical resection as the primary treatment, but with advanced T stage, complete resection with pathologically negative margins might be difficult to achieve. Induction chemotherapy helps achieve the balance between resection and morbidity in locally advanced technically unresectable tumors. The aim of this study was to analyze the impact of surgery in locally advanced, technically unresectable oral cavity cancers after neoadjuvant chemotherapy (NACT). Materials and Methods A retrospective analysis of patients with borderline resectable, locally advanced oral cavity cancers who were given NACT between February 2017 and December 2021 was conducted. Data regarding clinical and pathological characteristics, NACT, surgery, adjuvant therapy, and recurrences was analyzed. Results Of the 69 patients in the study, 69.6% had tongue cancer, rest were gingivobuccal complex cancers. All tumors were resected based on the post-NACT tumor volume and clear margins were achieved in 42% of cases. About 85.4% of the tongue cancers required a lesser resection than anticipated, thereby following the concept of organ and functional preservation post-NACT as proposed by Licitra et al. About 30.4% had ypT0 and 17.4% had ypN0. Recurrence and survival rates noted in our study were comparable to those reported in literature. Lymph node density of more than or equal to 0.07 was found in all recurrent cases. Conclusions Induction chemotherapy offers a chance of achieving adequate surgical resection while reducing morbidity and improving functional outcomes for patients with technically unresectable oral cavity cancers. Nodal disease may not respond to chemotherapy as well as the primary tumor. There is a need for comprehensive evaluation of prognostic factors, which could help identify the patients who will most benefit with NACT.
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We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Docetaxel/uso terapêutico , Epirubicina/uso terapêutico , Cisplatino/efeitos adversos , Platina/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Taxoides/efeitos adversos , Resultado do Tratamento , Ciclofosfamida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia NeoadjuvanteRESUMO
PURPOSE: Total neoadjuvant therapy (TNT) with pre-operative chemotherapy and chemoradiotherapy results in improved survival and is becoming the new standard of care in locally advanced rectal cancer (LARC). We describe our experience with TNT consisting of induction chemotherapy followed by chemoradiotherapy using full dose 5FU without oxaliplatin. METHODS: Adults with biopsy-proven, newly diagnosed LARC with high-risk characteristics on pelvic MRI (T4a or T4b, extramural vascular invasion, N2, mesorectal fascia involvement, enlargement/tumor deposits on lateral lymph nodes) were included. The TNT protocol comprised of six biweekly courses of modified FOLFOX6 followed by pelvic RT with four concurrent cycles of biweekly 5-FU 2600 mg/m2 + LV 200 mg/m2 without oxaliplatin to complete 20 uninterrupted weeks of full dose 5FU. Surgery was planned 11-13 weeks after completing chemoradiotherapy. RESULTS: Eighty-four LARC patients, including 26% with signet-ring cell carcinoma, with high-risk MRI characteristics were treated with the TNT protocol with a 96% completion rate. Significant (> grade 3) toxicities included neutropenia (23.8%), diarrhea (14.2%) anemia (10.7%), and two deaths. The median DFS at 2 years was 22.5 months with better survival noted for those who underwent surgery or had cCR (with NOM) compared to those who did not undergo surgery (due to progression, inadequate regression, or patient preference despite residual disease) -mDFS 27.7 months versus 11.4 months, p = < 0.0001 and mOS 29.2 months versus 15 months p = < 0.0001. CONCLUSION: The hybrid TNT regimen was administered without significant dose delays or interruptions. Toxicity was manageable but with two treatment-related deaths. Ability to undergo surgery after TNT predicted for improved DFS and OS.
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Aim: This study aimed to identify DPYD variants and the related but previously unexplored phenotype (plasma uracil, dihydrouracil [DHU], and the DHU-to-uracil ratio) in a healthy adult Indian population. Methods: Healthy adult volunteers (n = 100) had their uracil and DHU levels measured and were genotyped for selected variants. Results: Among the nine variants studied, c.1906-14763G>A and c.85T>C were the most prevalent. Participants with any of the variants except for c.85T>C and c.1627A>G had a significantly lower DHU-to-uracil ratio and those with c.1905+1G>A variant had significantly increased uracil concentration compared with wild-type. Conclusion: Participants with five variants were identified as having altered phenotypic measures, and 40% of the intermediate metabolizers had their phenotype in the terminal population percentiles.
Background: 5-fluorouracil (5-FU) is a medicine used in cancer treatment. It is eliminated from body by the enzyme DPD. Identifying deficiency in DPD before initiating 5-FU can save patients from oral, intestinal, and bone marrow toxic effects. Methods: The uracil and dihydrouracil (DHU, produced by DPD enzyme action) levels were measured and DPD gene (for identifying defects) was sequenced in 100 healthy adults. Results: Participants with DPD gene sequence that is known to be defective had higher plasma uracil levels and a low DHU-to-uracil ratio compared with those who did not have a defective gene. Conclusion: Measuring plasma uracil and DHU-to-uracil ratio can help identify people with defective DPD genes.
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Di-Hidrouracila Desidrogenase (NADP) , Uracila , Humanos , Di-Hidrouracila Desidrogenase (NADP)/genética , Genótipo , FenótipoRESUMO
BACKGROUND: One needs to choose wisely between primary neoadjuvant chemotherapy and primary cytoreductive surgery in ovarian cancer. The aim was to determine the recurrence free survival and overall survival after surgery for epithelial ovarian cancer and also the risk factors for recurrence and death. METHODS: Electronic medical records of 322 women operated for ovarian, fallopian or primary peritoneal cancer between 2011 and 2015table were reviewed. Descriptive statistics were used to describe patients and their clinical outcomes. Cox proportional hazard models were used for risk factor analysis. Adjusted hazard ratios were obtained for recurrence and death, adjusted for stage, primary treatment modality, residual disease and histology. Kaplan-Meier curves were drawn for probability of recurrence-free survival and overall survival. The log rank test was used to compare survival probabilities. RESULTS: The majority were stage III or stage IV (78%), serous histology (71%) and high grade (64%). Primary cytoreduction was done in 48% and interval cytoreduction in 52%. The median duration of follow up (survival) was 77 months (95% CI 72-82). There were 179 known recurrences (55.6 %). The estimated median time to recurrence was 22 (95% CI 14.5- 29.5) months. The independent risk factors for recurrence were neoadjuvant chemotherapy [HR 2.14, 95% CI 1.48-3.09], stage III/IV [HR 2.75; 95% CI 1.40-5.41], high grade serous histology [HR 1.69; 95% CI 1.12-2.54] and sub-optimal debulking [HR 3.15, 95% CI 2.19-4.55]. There were 78 known deaths (24.2 %) with a mean time to death of 24.3 (SD 16.1) months. The independent risk factors for death were sub-optimal debulking [HR 3.07; 95% CI 1.78-5.29] and stages III and IV cancer [HR 3.07; 95% CI 1.14-8.27]. CONCLUSIONS: Most ovarian cancers recur within 2 years. Risk factors for mortality are advanced stage and sub-optimal debulking. Maximal efforts at down staging and surgical resection will increase survival.
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Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Modelos de Riscos Proporcionais , Terapia Neoadjuvante/efeitos adversos , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Hospitais , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
Context Growing teratoma syndrome (GTS) is a rare entity seen following chemotherapy for metastatic nonseminomatous germ cell tumors, characterized by increase in size of the metastatic deposits, with normal serum tumor markers. Aims In this article, we aim to describe the various clinicoradiological presentations of GTS treated at our center. Design All patients who satisfied the GTS criteria from 2001 to 2019 were included. Characteristic imaging appearances along with sites of primary lesion and metastatic disease, stage and risk stratification at diagnosis, details of chemotherapy, details of surgical treatment and histopathology, levels of tumor markers, serum ß-human chorionic gonadotropin, lactate dehydrogenase, and alpha fetoprotein levels at baseline and at the end of all chemotherapy were analyzed. Results The significant radiological findings observed were an increase in the fat and cystic components and appearance of coarse calcifications within the lesions. Majority of the cases were male patients (87.5%) with testicular primaries and GTS transformation in nodal metastases being the most common occurrence (75%). All eight cases (100%) showed an increase in size and cystic component, whereas four out of eight cases (50%) had presence of internal septations and internal calcification. Conclusion Early recognition of this entity and clinical decision making through serial radiological imaging are of utmost importance as these growing deposits are resistant to chemotherapy and radiotherapy, with complete surgical excision being the only curative and definitive treatment option.
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BACKGROUND: The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice. METHODS: We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy. RESULTS: All (n = 5) had Naranjo scores of 6-7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2-4 days). All patients improved after conservative management with complete neurological recovery. CONCLUSION: Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions.
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Leucoencefalopatias , Neoplasias , Antimetabólitos Antineoplásicos/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/tratamento farmacológico , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: Dose-dense chemotherapy improves survival but with increased toxicity and treatment-related cost. We report the prevalence of anemia and the possible risk factors associated with chemotherapy-related anemia and determine the cost and time-delay associated with transfusion requirement in Indian patients with non-metastatic breast cancer on dose-dense preoperative chemotherapy. METHODS: In this study, triple-negative breast cancer (TNBC) patients were treated preoperatively with docetaxel and cyclophosphamide alternating with epirubicin and cisplatin every 2 weeks. Patients were evaluated for anemia pre- and post-chemotherapy. We examined trends in the red cell indices, transfusion requirement, time to transfusion, as well as risk factors associated with transfusion during treatment, along with delay in treatment due to anemia and the additional cost incurred. RESULTS: A total of 116 consecutive women with nonmetastatic TNBC were treated with preoperative chemotherapy. The median age was 44.5 years. 56.1% of patients had stage III disease. Anemia was detected at baseline in 54 (46.5%) patients with mild anemia (10-12 g/dl) in 42 (36.2%) patients and moderate anemia (8-10 g/dl) in 12 (10.3%) patients. During the course of treatment, all patients developed anemia. A total of 44 patients (37.9%) required transfusion during chemotherapy, with 55(47.4%) patients developing grade 1-2 anemia and 40 (34.5%) patients developing grade 3 anemia. The factors associated with anemia requiring transfusion were a steeper decline in hemoglobin after two cycles (OR 1.65, p = 0.02), low-grade tumor (OR 2.48, p = 0.03), and thrombocytopenia grade 3 or 4 (OR 4.35, p = 0.034), of which tumor grade and thrombocytopenia remained significant in multivariate analysis. Nearly one-fourth of the study population had a delay between two cycles of chemotherapy due to anemia. A median additional cost of INR 7000 was incurred among those requiring blood transfusion. CONCLUSION: Anemia is a common toxicity associated with dose-dense chemotherapy during curative breast cancer treatment leading to delay in treatment and increased cost. Low-grade tumor, grade 3 or 4 thrombocytopenia, and grade 2 or higher anemia after two cycles of chemotherapy are risk factors for blood transfusions during treatment.
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Anemia , Neoplasias da Mama , Trombocitopenia , Neoplasias de Mama Triplo Negativas , Adulto , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Anemia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transfusão de Sangue , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Epirubicina , Feminino , Humanos , Prevalência , Fatores de Risco , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
Anjana JoelContext Patients with seminoma present with advanced disease. End-of-treatment (EOT) positron emission tomography-computed tomography (PET-CT) is done to assess response and direct management of post-chemotherapy residual masses. Purpose This article assesses the utility of EOT PET-CT in the management of post-chemotherapy residual lymph nodal masses seminoma. Materials and Methods We analyzed all patients with seminoma who underwent an EOT PET-CT from January 2015 to January 2020 at our center and calculated the positive predictive value (PPV) and negative predictive value (NPV) of EOT PET-CT in the entire cohort of patients and among subgroups. Results A total of 34 male patients underwent EOT PET-CT. Fourteen (41.2%) were stratified as good risk and 20 (58.8%) as intermediate risk. The median follow-up was 23 months (interquartile range: 9.75-53 months). In 23 patients there were residual masses of size more than 3 cm at the EOT PET scan. EOT PET was positive as per the SEMPET criteria in 18 (78%) out of 23 patients. None underwent retroperitoneal lymph node dissection. All four who underwent image-guided biopsy, showed only necrosis on pathology. One patient with positive mediastinal node (standardized uptake value 13.6) had granulomatous inflammation. There was no relapse or progression during this period of follow-up. The NPV for EOT PET-CT for the entire cohort, > 3 cm, and > 6 weeks cutoff were 100%, respectively. The PPV for EOT PET-CT for the entire cohort, > 3 cm residual mass, and > 6 weeks cutoff were 8.7, 11.11, and 6.67%, respectively. Conclusion EOT PET-CT has a low PPV and high NPV in predicting viable tumor in post-chemotherapy residual masses among patients with seminomatous germ cell tumors. If required, EOT PET positivity can be confirmed by a biopsy or reassessed with a repeat PET-CT imaging to document persistent disease prior to further intervention.
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BACKGROUND: Adjuvant chemotherapy after surgery for gastric cancer improves survival but is difficult to administer due to poor tolerance. Combination chemotherapy with Docetaxel (Taxotere), Oxaliplatin (Eloxatin) and Capecitabine (Xeloda) (TEX) is used in the treatment of advanced gastric cancer. The efficacy and tolerability of this regimen (TEX) post resection of gastric cancer have not been studied. MATERIALS AND METHODS: Patients diagnosed with gastric adenocarcinoma, post resection without any prior chemotherapy between July 2007 and May 2011 and treated with TEX regimen administered as T 35 mg/m2 and E 50 mg/m2 on days (d) 1, 8 and X 625 mg/m2 bid (twice daily) on d 1-14 every 21 days were included in this retrospective analysis. Patient's electronic medical records were studied and data on tolerance, progressionfree survival (PFS) and overall survival (OS) was collected. RESULTS: Fifty-eight patients were treated with adjuvant TEX chemotherapy, majority 40 (68%) had distal gastric cancer. All patients underwent a D1 gastrectomy, and resection was performed for 44 (75%). Only 14 (24%) patients had more than 15 nodes studied in the resected specimen. Distribution for stages I, II and III is 14 (24%), 30 (52%) and 14 (24%), respectively. After a median follow-up of 40 months, the 3-year relapse free survival was 58% (95% CI: 42-68), and estimated median OS was 71 months (95% CI: 19-123 months). Twenty-three (40%) required dose reduction due to toxicity. Grade 3 or 4 toxicity was recorded for 22 (37%). Half (52%) of patients completed all planned chemotherapy of six cycles. CONCLUSION: Post resection of gastric adenocarcinoma adjuvant triplet TEX chemotherapy is a feasible and effective outpatient regimen. Diarrhoea, neutropenia and neuropathy were the common dose limiting toxicity. Post-surgery only half the numbers of patients are able to complete all planned cycles.
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In this retrospective analysis of 36 patients with recurrent ovarian cancer (ROC) treated with platinum pemetrexed doublet ± bevacizumab, the median age was 54.5 years (47-60) and 33 (91.7%) had serous histology. The overall response rate [ORR = complete (CR)+partial (PR) response] was 83.3%. At a median follow-up of 16 months, the median PFS was 13.8 months (95% CI: 10.849-20.580) and median OS 30.6 months, (95% CI: 21.46 months-NR). The incidence of Grade 3/4 anemia, thrombocytopenia, neutropenia and non-hematological toxicity was 19.4%, 3.9%, 16.6%, and 8.3%. Platinum pemetrexed chemotherapy in ROC is safe and effective treatment option.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Pemetrexede/administração & dosagem , Bevacizumab/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Pemetrexede/efeitos adversos , Estudos RetrospectivosRESUMO
Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.
Assuntos
Carcinoma Neuroendócrino , Ureter , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/radioterapia , Quimioterapia Adjuvante , Cisplatino , Humanos , Masculino , Terapia Neoadjuvante , Recidiva Local de NeoplasiaRESUMO
Palbociclib is a cyclin dependent kinase (CDK) 4/6 inhibitor that is indicated in combination with an aromatase inhibitor for first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2 -negative advanced or metastatic breast cancer. The commonly described side effects of palbociclib are neutropenia, anaemia, thrombocytopenia, fatigue, nausea, stomatitis, alopecia, diarrhoea, decreased appetite, vomiting, asthenia, peripheral neuropathy and epistaxis. However, post approval, increasing use of this drug has revealed another potentially fatal complication, in the form of pneumonitis, especially in the Asian population. The PALOMA 3 trial showed that rates of grade 3 and grade 4 adverse events were modestly higher in Asians than non-Asians, though palbociclib exposure was similar in both races. From this, we could infer that adverse effects of this drug must be monitored more specifically in individual racial populations. We report a patient who developed pneumonitis while on palbociclib and discuss the possible mechanisms and management of CDK 4/6 inhibitor-related lung injury.
RESUMO
BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with poor prognosis and access to anti-HER2 treatment is still a challenge in lower-middle income countries. The availability of the biosimilar trastuzumab has improved access by lowering the costs. We report the pattern of use of neoadjuvant ± adjuvant trastuzumab and outcomes in patients with HER2-positive non-metastatic breast cancer treated with regimens incorporating shorter durations of therapy and the use of the biosimilar trastuzumab compared to the innovator. METHODS: We conducted a retrospective analysis of patients with non-metastatic HER2-positive breast cancer treated with neoadjuvant ± adjuvant trastuzumab (innovator (n = 34 (33%)) and biosimilar (n = 70 (67%)) manufactured by Biocon Biologics) with chemotherapy. Information regarding chemotherapy regimens, duration of trastuzumab use (≤12 weeks and >12 weeks), pathological response (Miller Payne grade), disease free survival (DFS), overall survival (OS) and safety data were collected from electronic medical records. RESULTS: A total of 135 patients were analysed with a median age of 51 years (range: 23-82); of these, 57% were postmenopausal, 31.8% were hormone receptor positive and 62.9% had stage III disease. The overall pathological complete response (p-CR) in both breast and axilla increased to 37.6% in patients treated with trastuzumab preoperatively as compared to 22.2% in patients who did not receive any trastuzumab. Patients receiving innovator trastuzumab and biosimilar trastuzumab showed a p-CR of 28.5% and 41.7%, respectively. At a median follow-up of 42 months (range: 3-114), there were 18 relapses and 11 deaths. The 3-year DFS was 87.1% and OS was 92.2%. Cardiac dysfunction developed in 4 of 78 (5.1%) evaluable patients. CONCLUSION: Access to anti-HER2 therapy in the treatment of non-metastatic HER2-positive breast cancer in resource-constrained settings has improved significantly with the availability of the biosimilar trastuzumab. Imbalances in patient profiles at baseline in routine clinical practice led to inconclusive outcomes of ≤12 weeks versus >12 weeks trastuzumab treatment. However, on the basis of historical data, patients could be offered shorter duration of trastuzumab when a standard 1-year treatment of adjuvant trastuzumab is not feasible in resource-constrained settings. The p-CR using the biosimilar trastuzumab in neoadjuvant treatment has been observed to be comparable to the innovator trastuzumab.