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1.
Breast ; 60: 177-184, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34655887

RESUMO

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

2.
J Clin Oncol ; 39(33): 3682-3692, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34506246

RESUMO

PURPOSE: Postoperative Adjuvant Radiation in Cervical Cancer (PARCER), a phase III randomized trial, compared late toxicity after image-guided intensity-modulated radiotherapy (IG-IMRT) with three-dimensional conformal radiation therapy (3D-CRT) in women with cervical cancer undergoing postoperative radiation. METHODS: Patients were randomly assigned to receive either IG-IMRT or 3D-CRT after stratification for the type of hysterectomy and use of concurrent chemotherapy. The primary end point was 3-year grade ≥ 2 late GI toxicity assessed using Common Toxicity Criteria for Adverse Events v 3.0 and estimated using time-to-event, intention-to-treat analysis, with a study level type I error of 0.05 and a nominal α of .047 after accounting for one interim analysis. Secondary end points included acute toxicity, health-related quality of life, and pelvic relapse-free, disease-free, and overall survival. RESULTS: Between 2011 and 2019, 300 patients were randomly assigned (IG-IMRT 151 and 3D-CRT 149). At a median follow-up of 46 (interquartile range, 20-72) months, the 3-year cumulative incidence of grade ≥ 2 late GI toxicity in the IG-IMRT and 3D-CRT arms were 21.1% versus 42.4% (hazard ratio [HR] 0.46; 95% CI, 0.29 to 0.73; P < .001). The cumulative incidence of grade ≥ 2 any late toxicity was 28.1% versus 48.9% (HR 0.50; 95% CI, 0.33 to 0.76; P < .001), respectively. Patients reported reduced diarrhea (P = .04), improved appetite (P = .008), and lesser bowel symptoms (P = .002) with IG-IMRT. However, no difference was observed in the time by treatment interaction. The 3-year pelvic relapse-free survival and disease-free survival in the IG-IMRT versus the 3D-CRT arm were 81.8% versus 84% (HR 1.17; 95% CI, 0.68 to 1.99; P = .55) and 76.9% versus 81.2% (HR 1.03; 95% CI, 0.62 to 1.71; P = .89), respectively. CONCLUSION: IG-IMRT results in reduced toxicity with no difference in disease outcomes.

3.
PLoS One ; 16(7): e0253722, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34292933

RESUMO

BACKGROUND: There is scant data from India on efficacy and safety of palbociclib and ribociclib in routine clinical practice. METHODS: This retrospective, observational, single institution study included patients with estrogen and/or progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancers, who received palbociclib or ribociclib with any partner endocrine therapy in any line of treatment between January 2016 and June 2019. Data were analyzed for progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: The study included 101 female patients with median age of 57 (IQR 48-62) years, of whom 80 (79.2%) were postmenopausal, 79 (78.2%) received palbociclib or ribociclib in second- or later-line treatment, 59 (58.4%) received fulvestrant and 41 (40.6%) received an aromatase inhibitor. In first-line treatment, at a median follow-up of 21.7 (0.5-41.9) months, median PFS and OS were 21.1 (95%CI 16.36-not estimable) months and not reached, respectively. In second- or later-line setting, at a median follow-up of 17.2 (0.5-43.7) months, median PFS and OS were 5.98 (95%CI 4.96-7.89) months and 20.2 (95%CI 14.1-not estimable) months, respectively. Grade 3-4 neutropenia and febrile neutropenia were seen in 45 (45.0%) and 9 (9.0%) patients, respectively while dose reduction was required in 32 (31.7%) patients. In multivariable Cox regression analysis, first-line setting (HR 0.49, 95%CI 0.25-0.97, p = 0.043) and ECOG performance status 1 (HR 0.43, 95%CI 0.20-0.91, p = 0.028) were significantly associated with PFS while only ECOG PS 1 was significantly associated (HR 0.04, 95%CI 0.008-0.206, p = 0.000) with OS. CONCLUSION: Palbociclib and ribociclib, when used in routine clinical practice in first or subsequent lines of treatment, resulted in efficacy and toxicity outcomes in concordance with those expected from pivotal trials.


Assuntos
Aminopiridinas/administração & dosagem , Neoplasias da Mama , Piperazinas/administração & dosagem , Purinas/administração & dosagem , Piridinas/administração & dosagem , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Idoso , Aminopiridinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Piperazinas/efeitos adversos , Purinas/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
4.
Adv Radiat Oncol ; 6(6): 100725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34075350

RESUMO

Purpose: To report real-world compliance to radiation in gynecologic cancers during the complete lockdown phase of COVID-19 pandemic. Methods and Materials: From March 23, 2020, until June 30, 2020, complete lockdown was imposed in India. During this period there was restructuring of cancer care and radiation oncology department due to operational policies prevalent in the institution, and the care for gynecological cancer was based on the evolving international recommendations. Institutional review board approval was obtained to audit patterns of care during the complete lockdown phase. Descriptive variables were used to report on patient characteristics, compliance, delays, toxicity, and observed deviations in recommended care. Results: During the lockdown period spanning 100 days, treatment of 270 and telephonic follow-up of 1103 patients with gynecological cancer was undertaken. Of 270 new patients, due to travel restrictions, 90 patients were referred to the facilities in vicinity of their residence. Of the remaining 180 patients, 138 were planned for complete treatment at our institution and 42 were referred to our center for brachytherapy. Of 138 patients, only 106 (76%) completed the planned external radiation. Twenty-four (26%) patients completed full course of concurrent chemotherapy, 11 (12%) received chemotherapy dose reduction, and 57 (62%) received no concurrent chemotherapy. Treatment delay of up to 3 weeks was noted in 8.6% patients due to COVID-19 infection. No grade 4 to 5 acute sequelae were observed. No excess adverse effects were observed in high-risk population. Low rate of symptom burden was observed among 1103 patients on telephonic follow-up. With 100 (9.6%) patients reporting symptoms, among these, 54% (54 of 100) had complete resolution of symptoms within 4 weeks of teleconsultation, and 10% had disease progression. Conclusions: Low compliance with planned treatment was observed for radiation and concurrent chemotherapy due to lockdown and fear of contracting COVID-19 and will likely lead to increased risk of cancer-related mortality. Rapid restructuring of care is needed to prevent the same as COVID-19 pandemic further evolves.

5.
Int J Radiat Oncol Biol Phys ; 111(3): 826-834, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34146636

RESUMO

PURPOSE: A prospective phase 2 study was conducted to evaluate the feasibility and safety of single-application multifractionated (SA-MF), high-dose-rate (HDR), image guided adaptive brachytherapy (IGABT) for cervical cancer. METHODS AND MATERIALS: Patients (N = 41) with International Federation of Gynaecology and Obstetrics 2009 stage IIB-IVA disease recruited between 2017 and 2019 underwent SA-MF. After completion of external beam radiation therapy of 50 Gy in 25 fractions, patients received magnetic resonance IGABT. The IGABT protocol consisted of a single brachytherapy (BT) application and treatment with 3 fractions of HDR (9 Gy on day 1; 2 fractions of 7 Gy with a minimum 6-hour gap on day 2) after achieving planning aims of the high-risk clinical target volume (HRCTV) receiving >84 Gy EQD2 and 2 cm3 of the bladder and rectum/sigmoid receiving ≤85 Gy and <71 Gy, respectively. Interfraction variation was addressed by performing computed tomography planning and coregistration using a mutual information-based coordinate system on day 2 before the second fraction. Organ at risk contouring was done on computed tomography, and doses were re-evaluated and reoptimized if required. RESULTS: Thirty-eight patients were treated as per the protocol. All patients underwent Intracavitary + Interstitial BT with needles (median, 4; range, 3-11). The mean ± standard deviation HRCTV volume was 41 ± 21 cm3 and HRCTV D90 dose was 87.2 ± 3.6Gy. The 0.1 cm3 and 2 cm3 to bladder, rectum, and sigmoid were -103.2 ± 10.6 Gy and -84.6 ± 6.8 Gy, 82.2 ± 9.5 Gy and -68.3 ± 5.7 Gy, and 83.5 ± 9.8 Gy and -69.5 ± 5.9 Gy, respectively. Six patients required reoptimization before the second fraction to meet planning aims. Mean overall treatment time was 47 ± 6 days. With a median follow up of 22 months (range, 2-37), 2-year local control and disease-free and overall survival were 90.1%, 85%, and 94.5%, respectively. So far 1 patient with grade II and 2 patients with grade III rectal toxicities have been reported. CONCLUSION: Magnetic resonance IGABT with SA-MF BT was feasible in 95% of patients. The dosimetric parameters and clinical results achieved so far look promising.

6.
BMJ Open ; 11(6): e047376, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187825

RESUMO

IMPORTANCE: The Cancer Aging Research Group (CARG) toxicity score is used to assess toxicity risk in geriatric patients receiving chemotherapy. OBJECTIVE: The primary aim was to validate the CARG score in geriatric patients treated with curative intent chemotherapy in predicting grade 3-5 toxicities. DESIGN: This was a longitudinal prospective observational study. SETTING: Tata Memorial Hospital, Mumbai, India, a tertiary cancer care referral centre. PARTICIPANTS: Patients, aged ≥65 years, with gastrointestinal, breast or gynaecological stage I-III cancers being planned for curative intent chemotherapy. A total of 270 patients were required for accrual in the study. EXPOSURES: Total risk score ranged from 0 (lowest toxicity risk) to 19 (highest toxicity risk). MAIN OUTCOMES AND MEASURES: The primary endpoint of the study was to evaluate whether the CARG risk score predicted for grade 3-5 toxicities. RESULTS: The study cohort of 270 patients had a mean age of 69 (65-83) years, with the most common cancers being gastrointestinal (79%). Fifty-two per cent of patients had atleast one grade 3-5 toxicity. The risk of toxicity was increased with an increasing risk score (42% low risk, 51% medium risk and 79% high risk; p<0.001). There was no association between either Eastern Cooperative Oncology Group (ECOG) performance status (p=0.69) or age-adjusted Charlson Comorbidity Index (p=0.79) risk categories and grade 3-5 chemotherapy toxicities. CONCLUSIONS AND RELEVANCE: This study validates the CARG risk score in predicting for grade 3-5 toxicities in geriatric oncology patients receiving curative intent chemotherapy and can be considered as the standard of care before planning chemotherapy in every elderly patient. TRIAL REGISTRATION NUMBER: CTRI/2016/10/007357; Results.


Assuntos
Antineoplásicos , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Índia , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Medição de Risco
7.
Indian J Cancer ; 58(3): 365-370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33753596

RESUMO

Background: In metastatic soft tissue sarcoma (M-STS), pazopanib has demonstrated promising activity; however, there is dearth of data from lower and middle income countries. It is important to explore the feasibility (toxicity, acceptance), efficacy (response rates, survival), and optimal dose requirement of pazopanib in M-STS in India. Methods: All patients who received pazopanib for M-STS in 2013-2018 in Tata Memorial Centre were included. Institutional ethics committee approval was obtained. Assessment for response with contrast computed tomography scans was done as per the response evaluation criteria in solid tumors (RECIST) 1.1 criteria. Pazopanib was continued until progression or unacceptable toxicity. Clinical benefit rates and survival were evaluated by Kaplan-Meier method. All statistical calculations were done using SPSS version 21.0. Results: Seventy-two consecutive patients with a median follow-up of 17 (4-40) months were included in this study. Median lines of prior therapy were 2 (0-2). Among 50 evaluable patients, there were 12/50 (24%) partial responses, 25/50 (50%) stable disease, and 15/50 (30%) progressive disease. Median progression-free survival was 5 (95% confidence interval (CI) 3-6.9) months and median overall survival was 11 (95% CI 6.8-15.2) months. Adverse effects (G2/G3) in patients: hand foot syndrome-28%, hyperbilirubinemia/transaminitis-10%, diarrhea-20%, hypertension-17%, hypothyroidism-15%, anemia-6%, and fatigue-17%. Notably, 40% patient required dose reduction and median dose was 600 (200-800) mg daily. Conclusion: Pazopanib was found a feasible treatment option for M-STS in India with internationally comparable outcomes. However, significant patients required dose modifications, and median tolerated dose was lower than the standard 800 mg dose. This novel finding merits confirmation in larger cohorts for reproducibility.

8.
Indian J Cancer ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33753616

RESUMO

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

9.
Indian J Cancer ; 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33753630

RESUMO

Background: In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients. Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH. Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6-60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2-11.6) usage of HER2-targeted therapy in the 2008 cohort. Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

10.
Breast ; 56: 88-95, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640524

RESUMO

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.


Assuntos
Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Idade Gestacional , Humanos , Incidência , Índia/epidemiologia , Mastectomia , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Prognóstico , Receptor ErbB-2 , Sistema de Registros , Análise de Sobrevida
11.
Indian J Cancer ; 57(4): 416-422, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33078748

RESUMO

Background: There is paucity of outcome data of patients with cervical cancer presenting with malignant obstructive uropathy. The present retrospective study describes outcomes of patients with cervical cancer who presented with obstructive uropathy at the time of diagnosis and underwent urinary diversion with percutaneous nephrostomy (PCN) before/during treatment. Methods: Patients who underwent PCN from January 2010 to June 2015 were included. Intent of treatment (radical or palliative) was decided within multidisciplinary team depending on disease stage, Karnofsky performance status (KPS), and degree of renal derangement. Treatment and outcome details were retrieved from electronic records. Time to normalization of creatinine, feasibility of delivering planned treatment, and overall survival (OS) were determined. Impact of various prognostic factors on outcomes was determined using univariate or multivariate analysis. Results: After PCN and double-J stenting, 50% were eligible for (chemo) radiation. All radically treated patients (26/52) received brachytherapy. The median EQD2 to point A was 78 Gy (72-84 Gy). The median OS was 10 (0.5-60) months. Patients who completed chemoradiation had median OS of 31 months. Those receiving radical radiation and palliative radiation had median OS of 11 and 6 months, respectively. On univariate analysis, smaller tumor size (p = 0.03), high KPS (P = 0.04), and radical intent of treatment (P = 0.05) predicted for OS. Conclusion: Patients presenting with obstructive uropathy have median OS less than a year despite urinary diversion. Select cohort with good performance status, small tumor size, and serum creatinine of ≤3 mg/dL may be selected for diversion procedures and potential radical treatment.


Assuntos
Braquiterapia/mortalidade , Quimiorradioterapia/mortalidade , Nefrostomia Percutânea/mortalidade , Obstrução Ureteral/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Obstrução Ureteral/complicações , Obstrução Ureteral/patologia , Obstrução Ureteral/terapia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
12.
Cancer Med ; 9(23): 8747-8753, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128509

RESUMO

BACKGROUND: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). PATIENTS AND METHODS: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. RESULTS: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. CONCLUSIONS: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.


Assuntos
Antivirais/uso terapêutico , COVID-19/prevenção & controle , Neoplasias/terapia , SARS-CoV-2/efeitos dos fármacos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias , Estudos Prospectivos , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Adulto Jovem
13.
Gynecol Oncol ; 159(2): 359-364, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32829963

RESUMO

OBJECTIVE(S): The objective of this study was to evaluate the clinical outcomes and prognostic factors affecting survival of cervical cancer patients presenting with lower third vaginal involvement. MATERIALS/METHODS: The patients with histologically proven invasive cervical cancer with clinical FIGO-2009 stage IIIA and IIIB with lower one-third vaginal involvement, treated with radio (chemo) therapy between 2010 and 2016 at our institution were retrospectively analyzed. RESULTS: There were 118 cervical cancer patients with lower third vaginal involvement with median age of 56.5 years (Range: 33-77 years). Forty-five patients were of FIGO stage IIIA, 73 patients staged as stage IIIB at diagnosis with predominant squamous histology. At a median follow up of 30 months, 12 patients (10.1%) developed local vaginal recurrences and 4 patients (3.3%) had developed loco regional recurrences, 27 patients (23%) developed distant and 2 patients developed loco-regional and distant relapses. The 3- year DFS and OS rates were 61.5% and 69.8% respectively. The 3-year DFS and OS of patients with IIIA was significantly better than IIIB patients (71% vs 56%, p: 0.02 and 76% vs 66%, p: 0.01 respectively) on univariate analysis. Concurrent chemotherapy and absence of persistent disease emerged as independent predictors of survival on multi-variate analysis. CONCLUSION: The outcome of patients with FIGO IIIA is better than IIIB with lower vaginal involvement. Elderly patients, patients not receiving concomitant chemotherapy and presence of residual disease at BT are associated with poorer outcomes.


Assuntos
Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Vagina/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Braquiterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia
14.
Int J Radiat Oncol Biol Phys ; 108(5): 1248-1256, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32681859

RESUMO

PURPOSE: In 2018, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging for cervical cancer. The present study was designed to reclassify patients with locally advanced cervix cancer and perform a comparative evaluation with FIGO 2009. METHODS AND MATERIALS: Patients with locally advanced cervical cancer (stage IB2-IVA) who had baseline cross-sectional imaging and received (chemo-) radiation and brachytherapy were included. Survival outcomes were analyzed according to FIGO 2009. Patients were then reclassified according to FIGO 2018, and TNM classification outcomes were analyzed. FIGO stage and known prognostic factors were included in univariate analysis, and multivariate analysis was performed to investigate the prognostic value of clinical stage. RESULTS: Six hundred thirty-two patients were included. Overall, 185 (29.3%) patients had pelvic adenopathy, and 51 (8.2%) had positive paraortic nodes. At a median follow-up of 33 months, 116 (18.3%) patients had recurrence. Three-year disease-free survival (DFS) according to FIGO 2009 for stage IB, IIA, IIB, IIIA, IIIB, and IVA was 86%, 91%, 76%, 57%, 65%, and 61%, respectively. The 3-year DFS after restaging according to FIGO 2018 for stage IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA was 100%, 93%, 84%, 53%, 77%, 74%, 61%, and 61%, respectively. Patients with clinically significant lymphadenopathy had inferior outcomes compared with node-negative patients (62.9% vs 77.8%; P = .002). Patients with ≥3 paraortic nodes had poorer DFS than patients with <3 paraortic lymphadenopathy (13.6% vs 56.3%; P = .001). Furthermore, patients with primary tumor volume >30 cm3 had worse 3-year DFS than those with primary tumor volume ≤30 cm3 (67.4% vs 78.5%; P = .002). CONCLUSIONS: FIGO 2018 modification is associated with heterogenous outcomes in node-positive patients that are affected by primary tumor and nodal volume. We propose a modification to the existing TNM staging system to allow more robust classification of outcomes.


Assuntos
Quimiorradioterapia , Estadiamento de Neoplasias/métodos , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Braquiterapia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Ginecologia , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Obstetrícia , Pelve , Prognóstico , Carga Tumoral , Neoplasias do Colo do Útero/classificação , Neoplasias do Colo do Útero/terapia
15.
Ann Diagn Pathol ; 47: 151558, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32619922

RESUMO

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Colorretais/complicações , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/genética , Imuno-Histoquímica/métodos , Síndromes Neoplásicas Hereditárias/complicações , Neoplasias Uterinas/patologia , Adulto , Idoso , Diferenciação Celular , Quimiorradioterapia Adjuvante/métodos , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Terapia Combinada , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/terapia , Estudos de Viabilidade , Feminino , Humanos , Histerectomia/métodos , Índia/epidemiologia , Metástase Linfática/patologia , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Miométrio/patologia , Gradação de Tumores/métodos , Salpingo-Ooforectomia/métodos
16.
Cancer Rep (Hoboken) ; 3(2): e1217, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32671995

RESUMO

BACKGROUND: One of the primary treatment strategies for advanced epithelial ovarian cancers includes neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy. Compliance to treatment is important to possibly improve outcomes. AIM: To audit treatment compliance and its effect on overall survival (OS) and disease free survival (DFS) in women undergoing IDS. METHODS AND RESULTS: Women diagnosed with advanced epithelial ovarian cancer undergoing IDS were included. Details of compliance to chemotherapy and surgery as per standard guidelines were assessed, and correlation with survival was studied. Reasons for protocol deviation at various levels were documented and analysed. A total of 182 patients were included. The total number of deviations was 134 with deviation at any level being 89 (48.9%) and at all levels 5%. Both patient- and treatment-related factors contributed towards deviation. Deviation or noncompliance towards treatment resulted in a significantly reduced 5-year OS (34.4% vs 58.2%; P = .001) compared with compliant patients, which retained its significance on multivariate analysis (P = .024) as well. CONCLUSION: Deviation from treatment guidelines resulted in a significantly lower 5-year OS compared with those who remained treatment compliant. Both patient- and treatment-related factors contributed towards noncompliance and hence towards lower survival.

17.
JCO Glob Oncol ; 6: 542-547, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32228315

RESUMO

PURPOSE: Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide. PATIENTS AND METHODS: Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity. RESULTS: Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity. CONCLUSION: Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.


Assuntos
Neoplasias Ovarianas , Platina , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Indazóis , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Platina/uso terapêutico , Pirimidinas , Estudos Retrospectivos , Sulfonamidas
18.
Turk Patoloji Derg ; 1(1): 261-267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149361

RESUMO

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) / malignant rhabdoid tumor of the ovary (MRTO) is a rare tumor affecting young women. It is frequently misdiagnosed due to overlapping morphological and immunohistochemical features with many other ovarian tumors. The prognosis of the tumors is very poor; hence an accurate diagnosis is of utmost importance. Recently, the loss of BRG1 protein by immunohistochemistry has been shown to be a useful diagnostic marker. We present here two cases of SSCOHT/MRTO, in young women 22 and 32 years of age, where several differential diagnoses were considered on morphology and immunohistochemistry but were confirmed as SCCOHT/MRTO by the demonstration of loss of BRG1. As the prognosis of SCCOHT is very dismal, and accurate diagnosis is of necessity, we recommend the inclusion of BRG1 immunohistochemistry in the diagnostic armamentarium of poorly differentiated ovarian tumors, particularly in young adults.


Assuntos
Carcinoma de Células Pequenas/patologia , DNA Helicases/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas/patologia , Tumor Rabdoide/patologia , Fatores de Transcrição/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Pequenas/metabolismo , Feminino , Humanos , Hipercalcemia/etiologia , Hipercalcemia/patologia , Neoplasias Ovarianas/metabolismo , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/patologia , Tumor Rabdoide/metabolismo , Adulto Jovem
20.
Ecancermedicalscience ; 13: 957, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31645885

RESUMO

Objective: Extended-field radiotherapy (EFRT) with concurrent chemotherapy represents standard treatment in cervical cancer patients with para-aortic lymph nodal (PALN) metastasis. While EFRT with Intensity Modulated RT (IMRT) has been demonstrated to reduce toxicities, the dose thresholds for minimizing acute toxicity is not clear. The present study was undertaken to report the early toxicity with extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix in our cohort of patients and determine dose-volume parameters that predict ≥grade II haematological toxicity and diarrhoea. Methodology: This was a retrospective study of consecutive cervical cancer patients with PALN metastasis treated with EF-IMRT. Patients received rotational IMRT +/- neoadjuvant chemotherapy (NACT) and/or concurrent chemotherapy (45-50 Gy/25#/5 weeks) followed by high-dose rate brachytherapy. Acute haematological and gastrointestinal toxicity (diarrhoea and vomiting) was correlated with doses received by bowel and marrow. Receiver operator characteristics curves were used for deriving thresholds that predict for increased toxicity and tested on univariate and multivariate analysis. Finally, disease free and overall survival (DFS and OS) was calculated. Results: A total of 43 patients were included. One-fourth of the patients (11/43) received NACT and 88% received concurrent chemotherapy. Within the upfront EF-IMRT cohort, 22.6% and 9.7% patients developed grade ≥III haematological (HT) and gastrointestinal (GI) toxicity respectively, with an increase in HT (≥ grade III HT =67%) in patients receiving NACT (p = 0.007). In the entire cohort bone marrow Volume receiving 10 Gy (V10>) 90% correlated with an increase in ≥ grade III HT (p = 0.05). No dose volume thresholds could be validated for GI toxicity. The OS and DFS at 2 years was 56% and 54%, respectively. Conclusion: EF-IMRT is a feasible option for cervical cancer patients with PALN involvement and is associated with acceptable grade III toxicity. Future studies need to focus on minimizing HT toxicity.

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