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1.
Radiother Oncol ; 164: 216-222, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34597737

RESUMO

BACKGROUND & PURPOSE: To evaluate the efficacy and toxicity of dose-escalated image guided-intensity modulated radiation therapy (IG-IMRT) in osteosarcoma (OGS), chondrosarcoma (CS) and chordoma (CH) of head and neck (H&N) and pelvis. METHODS AND MATERIALS: In this prospective non-randomized study, 65 patients of H&N or pelvic OGS (24), CS (7) and CH (34) mandating definitive or post-operative radiotherapy from May 2013 to December 2018 were included. Radiotherapy doses in definitive setting were 72.0 Gy for CH and 70.2 Gy for OGS and CS; while in post-operative setting it was 66.6 Gy and 64.8 Gy respectively (at 1.8 Gy per fraction). RESULTS: Planned doses of radiotherapy could be completed in 61 (93.8%) patients; with grade III or higher acute and late toxicities of 3% and 0% respectively. With a median follow-up of 52 (range 6-92) months, the five-year actuarial local control (LC) rates were 66% in OGS, 38.1% in CS and 75.9% in CH; while cause-specific survival (CSS) rates were 54.7%, 64.3% and 92.2% respectively. There was no statistically significant difference in outcomes for patients receiving definitive and post-operative radiotherapy. Locally controlled disease at first follow-up after radiotherapy was associated with improved CSS and OS in CS (p = 0.014) and CH (p < 0.001). Radiotherapy resulted in significant and sustained improvement in Musculoskeletal tumour society (MSTS) score and reduction in pain score. Salvage re-irradiation was feasible in local progression after radiotherapy, with good outcomes and tolerability. CONCLUSION: Dose-escalated IG-IMRT results in good LC & functional improvement with minimal toxicity in OGS, CS and CH.

2.
Front Oncol ; 11: 710585, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568037

RESUMO

Background: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). Patients and Methods: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). Results: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. Conclusions: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

3.
Head Neck Pathol ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34076846

RESUMO

Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma (SCC) that is characterized by minimal cytologic atypia and a unique deeply infiltrative growth pattern resembling rabbit burrows (cuniculi). With less than 75 cases reported in the head and neck, the clinical and pathologic spectrum of this entity remains poorly understood. A retrospective review of the clinical and pathologic features of archival cases of oral CC was performed. A total of six cases of oral CC were identified. Age ranged from 25-77 years; the male-to-female ratio was 5:1. All patients had a long-standing history of tobacco and betel-quid consumption. The tumors were distributed in the gingivobuccal sulcus (n = 2), the tongue (n = 2), buccal mucosa (n = 1), and the palate (n = 1). Histology in all cases typically revealed a tumor composed of well-differentiated squamous epithelium, devoid of atypia, lining deeply infiltrative, large-sized, branching, keratin-filled cavities, resembling rabbit-burrows. Dense lymphocytic infiltrates and discharging micro-abscesses were regular features. Underlying bone invasion and lymph node metastasis were observed in 1 patient. One patient with a tongue tumor developed locoregional recurrence at 10 months while none developed distant metastasis. Oral CC is a rare and under-recognized variant of SCC with locally aggressive behavior. Lack of familiarity with this variant exacerbated by the absence of cytologic anaplasia makes CC susceptible to multiple negative biopsies and erroneous diagnoses. Awareness of this clinicopathologic entity is essential to allow its accurate diagnosis and optimal management.

4.
Ann Diagn Pathol ; 53: 151763, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34111707

RESUMO

BACKGROUND: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent. DESIGN: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre. RESULTS: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course. CONCLUSION: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization.

5.
Ecancermedicalscience ; 15: 1166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33680080

RESUMO

Background: Multiple low-cost biosimilars of bevacizumab are now available but their clinical efficacy has never been compared against the original (innovator) molecule in glioblastoma. The aim of the current analysis is to compare the overall survival (OS) in recurrent/progressive glioblastoma patients between the biosimilar and innovator molecules. Materials and methods: Adult recurrent/progressive glioblastoma patients treated with bevacizumab from 1 July 2015 to 30 July 2019 were identified. These patients were either offered Bevacizumab innovator (Avastin, Roche) or biosimilar (BevaciRel: Reliance Life sciences or Bryxta: Zydus Oncosciences) depending upon the financial status and affordability of the patients. The primary endpoint of the study was OS, while progression-free survival (PFS) and adverse events were the secondary endpoints. Results: There were 82 patients, out of which 57 received innovator and 25 received biosimilar bevacizumab. At median follow-up of 26 months, the median PFS was 3.66 (95% confidence interval (CI) 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and biosimilar group, respectively (Log-rank test p-value = 0.072). The hazard ratio (HR) for progression was 0.61 (95% CI 0.35 to 1.05; p-value = 0.075). At the time of data cut-off, the median OS was 5.53 (95% CI, 5.07 to 5.99) versus 7.33 months (95% CI, 5.63 to 9.03) in innovator and biosimilar group, respectively (Log-rank test p-value = 0.51). The HR for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). The adverse events and safety profiles were comparable between the two groups. Conclusion: In the recurrent/progressive glioblastoma patients, both innovator and biosimilar bevacizumab seem to have similar safety and clinical efficacy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33741286

RESUMO

Carcinoma with dual neuroendocrine and non-neuroendocrine components are recognized albeit a rare occurrence among the head and neck tumours. Owing to a disjointed pathology taxonomy and a lack of defining criteria, these tumors have remained underrecognized and poorly understood by pathologists and oncologists. Herein, we present a heretofore unreported case of a mixed neuroendocrine non-neuroendocrine carcinoma occurring as a carcinoma ex-pleomorphic adenoma (CXPA) in the soft palate of a 32-year-old man. Histologic examination revealed 2 distinctive malignancies comprising salivary duct carcinoma (SDC) and small cell carcinoma (SmCC) arising in a background of a benign pleomorphic adenoma. On immunohistochemistry, the SDC cells were cytokeratin 7 positive, androgen receptor positive, GATA-3 (GATA binding protein 3) positive, and gross cystic disease fluid protein (GCDFP-15) positive and the SmCC cells were synaptophysin positive and chromogranin positive, confirming the presence of 2 different histologic malignancies. We report this case not only for its exceptional rarity but also to discuss the lacunae that exist in the current classification systems that might facilitate an erroneous categorization of these rare tumors. Standardization of nomenclature and defining criteria is imperative to ensure accurate diagnosis, optimal management, and a better understanding of the biology of these enigmatic tumors.


Assuntos
Adenoma Pleomorfo , Carcinoma de Células Pequenas , Carcinoma , Neoplasias das Glândulas Salivares , Adulto , Humanos , Masculino , Ductos Salivares , Neoplasias das Glândulas Salivares/diagnóstico por imagem
7.
BMJ Open ; 11(3): e043628, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727268

RESUMO

INTRODUCTION: Two-phase II randomised studies have shown a significant benefit of local consolidation therapy in oligometastatic non-small cell lung cancer (NSCLC). This phase III randomised controlled trial (RCT) will evaluate the efficacy of local consolidation radiation therapy (RT) in oligometastases (OM) NSCLC after completion of initial systemic therapy. METHODS AND ANALYSIS: This is a single-centre phase III RCT of OM NSCLC patients. One hundred and ninety patients will undergo 1:1 randomisation to either standard maintenance therapy (control arm) or local consolidation RT and standard maintenance therapy (experimental arm). Patients will be stratified into the number of OM sites (1-2 vs 3-5), nodal metastases (N0-N1 vs N2-N3) and presence or absence of brain metastases. Stereotactic body radiation therapy to all the oligometastatic sites and definitive RT to primary disease will be given in the experimental arm. The primary endpoint is overall survival and secondary endpoints include progression-free survival, local control of OM sites, new distant metastases free survival, objective response rate, toxicity and quality of life. Translation endpoint include circulating tumour cells and radiomics using texture analysis. ETHICS AND DISSEMINATION: All patients will be provided with a written informed consent form which needs to be signed before randomisation. The study is approved by the institutional ethics committee-II (project number 3445) and registered with Clinical Trials Registry-India, dated 21 April 2020. TRIAL REGISTRATION NUMBER: CTRI/2020/04/024761; Pre-Results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Índia , Neoplasias Pulmonares/radioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Padrão de Cuidado , Resultado do Tratamento
8.
J Vasc Interv Radiol ; 32(4): 504-509, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33612370

RESUMO

PURPOSE: To evaluate safety and long-term efficacy of radiofrequency (RF) ablation in treatment of chondroblastoma. MATERIALS AND METHODS: This retrospective analysis comprised 27 consecutive patients with histopathologically proven chondroblastoma treated by RF ablation. The tumors were located in the proximal humerus (n = 6), proximal tibia (n = 8), proximal femur (n = 6), distal femur (n = 5), acromion process (n = 1), and lunate (n = 1). In 19 patients (70.3%), the tumor was in the weight-bearing area of the bone. Clinical response was assessed by comparing pain scores and functional assessment by Musculoskeletal Tumor Society (MSTS) score before and after ablation. Patients were followed for a minimum of 1 year to rule out complications and recurrence. RESULTS: Technical success rate was 100%. Mean pain score before the procedure was 7.34 (range, 7-9); all patients experienced a reduction in pain, with 25 (92.6%) patients reporting complete pain relief at 6 weeks. Mean MSTS score before the procedure was 15.4, whereas mean MSTS score at 6 weeks after the procedure was 28.6, suggesting significant functional improvement (P < .0001). Two patients developed osteonecrosis and collapse of the treated bone. There were no recurrences. CONCLUSIONS: Percutaneous RF ablation is a safe and effective option for treating chondroblastoma of the appendicular skeleton.


Assuntos
Neoplasias Ósseas/cirurgia , Condroblastoma/cirurgia , Ablação por Radiofrequência , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/fisiopatologia , Criança , Condroblastoma/diagnóstico por imagem , Condroblastoma/patologia , Estudos de Viabilidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Complicações Pós-Operatórias/etiologia , Ablação por Radiofrequência/efeitos adversos , Radiografia Intervencionista , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
9.
Jpn J Clin Oncol ; 51(5): 762-768, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33521824

RESUMO

BACKGROUND: We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes. METHODS: Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015-September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan-Meier method and log-rank test were used for survival analysis. RESULTS: Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6-41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage. CONCLUSIONS: Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.


Assuntos
Neoplasias do Tronco Encefálico/radioterapia , Glioma Pontino Intrínseco Difuso/radioterapia , Qualidade de Vida/psicologia , Reirradiação/métodos , Neoplasias do Tronco Encefálico/mortalidade , Criança , Estudos de Coortes , Glioma Pontino Intrínseco Difuso/mortalidade , Feminino , Humanos , Masculino , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida
10.
Cancer Med ; 10(5): 1525-1534, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33591635

RESUMO

BACKGROUND: Checkpoint inhibitors (Nivolumab and Pembrolizumab) are approved for multiple indications in solid tumors. However access to these therapies is limited in low and middle income countries. Hence we performed an audit to identify accessibility, adverse event rates, compliance, progression free survival and overall survival in solid tumors. METHODS: This was a single center retrospective analysis of prospective data base of patients with non-melanoma solid tumors who were treated with immunotherapy from August 2015 to November 2018. Adverse events during immunotherapy were documented and graded using CTCAE (Common terminology criteria for adverse events), v. 4.02. The response rates to immunotherapy, toxicities and the time to onset and resolution of toxicities were also evaluated as secondary endpoints. RESULTS: Out of 9610 patients, only 155 patients (1.61%) could receive immunotherapy. The most common malignancies included metastatic non-small cell lung cancer, metastatic renal cell carcinoma, metastatic urothelial carcinoma and relapsed/recurrent head and neck squamous cell carcinoma. Median overall survival in patients who received immunotherapy in non-melanoma solid malignancies was 5.37 months (95% CI, 3.73-9.73). Poor performance status at baseline was the only adverse prognostic factor. The median progression free survival was 2.57 months (95% CI, 1.73-3.83). Immunotherapy was well tolerated with most common side effects being fatigue 14.8% and anorexia 5.8%. The cumulative incidence of immune related adverse events like hepatitis, pneumonitis, colitis and nephritis was less than 10%. CONCLUSION: Real-world data in Indian setting confirms the benefit of immunotherapy in patients with advanced non-melanoma solid tumors.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/induzido quimicamente , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Fadiga/induzido quimicamente , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/provisão & distribuição , Índia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto Jovem
11.
BMJ Open ; 11(2): e041345, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589450

RESUMO

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have significantly improved the progression-free survival (PFS) of metastatic non-small cell lung cancer (NSCLC) with oncogene mutations of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) compared with systemic therapy alone. However, the majority eventually develop resistance with a median PFS of 8-12 months. The pattern of failure studies showed disease relapse at the original sites of the disease-harbouring resistant tumour cells. METHODS AND ANALYSIS: This study is designed as a phase II randomised controlled trial to evaluate the efficacy of local consolidative radiation therapy (LCRT) in addition to TKI in upfront oligometastatic NSCLC. Patients will be screened at presentation for oligometastases (≤5 sites) and will start on TKI after confirmation of EGFR or ALK mutation status. After initial TKI for 2-4 months, eligible patients will be randomised in a 1:1 ratio with stratification of oligometastatic sites (1-3 vs 4-5), performance status of 0-1 versus 2 and brain metastases. The standard arm will continue to receive TKI, and the intervention arm will receive TKI plus LCRT. Stereotactic body radiation therapy will be delivered to all the oligometastatic sites.The primary end point is PFS, and secondary end points are overall survival, local control of oligometastatic sites, toxicity and patient-reported outcomes. The sample size calculation took a median PFS of 10 months in the standard arm. To detect an absolute improvement of 7 months in the interventional arm, with a one-sided alpha of 5% and 80% power, a total of 106 patients will be accrued over a period of 48 months. ETHICS AND DISSEMINATION: The study is approved by the Institutional Ethics Committee II of Tata Memorial Centre, Mumbai, and registered with Clinical Trials Registry-India, CTRI/2019/11/021872, dated 5 November 2019. All eligible participants will be provided with a participant information sheet and will be required to provide written informed consent for participation in the study. The study results will be presented at a national/international conference and will be published in a peer-reviewed journal.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Ensaios Clínicos Fase II como Assunto , Humanos , Índia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Oncogenes , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
J Clin Neurosci ; 84: 91-96, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33358093

RESUMO

Central neurocytoma is a rare benign brain tumor that typically arises from the subependymal lining of the lateral ventricles in young adults and is generally associated with excellent survival following neurosurgical excision alone. This is a retrospective clinical audit of biopsy-proven neurocytoma registered between 2004 and 2019 at a single institution in India. All time-to event outcomes were analyzed using Kaplan-Meier method and compared with the log-rank test. Any p-value <0.05 was considered statistically significant. A total of 66 patients with neurocytoma were included in the descriptive analysis. Median age of study cohort was 31 years with equitable gender ratio. Majority (83%) of tumors were intraventricular, lateral ventricle being the commonest location. Following maximal safe resection, patients were generally kept on close clinico-radiological surveillance. Most patients (80%) had typical World Health Organization (WHO) grade II neurocytoma with remaining 20% showing histological atypia and/or high-grade features. Outcome analysis was restricted to 35 patients with relevant treatment details and adequate follow-up information. Six patients experienced recurrent/progressive disease with 2 documented deaths. At a median follow up of 52 months, 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 93.3% and 96.8% respectively. Three patients developed delayed recurrence (>5-years after initial diagnosis) underscoring the importance of long-term follow-up. Atypical/high-grade histology was associated with inferior survival that may stand to benefit with upfront adjuvant radiotherapy. This represents the largest single-institution series of central neurocytoma and demonstrates excellent outcomes with adequate surgical resection alone, reserving radiotherapy for large residual tumor, recurrent disease, and/or atypical high-grade histology.


Assuntos
Neoplasias Encefálicas/patologia , Neurocitoma/patologia , Adulto , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Índia , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/radioterapia , Neurocitoma/mortalidade , Neurocitoma/cirurgia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Adulto Jovem
14.
J Adolesc Young Adult Oncol ; 10(2): 185-192, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32706630

RESUMO

Purpose: About 30%-35% of nonmetastatic and 60%-80% of metastatic Ewing Sarcoma (ES) will relapse post-treatment and outcomes after relapse continue to be poor over last several decades. Prognostic factors affecting survival after relapse of ES are also not robustly known. We present outcomes using a novel hybrid salvage protocol of four active chemotherapeutic agents in our cohort of patients after relapse of ES. Methods: This is a retrospective analysis of all consecutive relapsed ES patients treated with curative intent over 4 years (January 2012 to December 2015). All received 12-cycles of hybrid chemotherapy regimen with surgery/radiotherapy done after first 4 cycles. Event-free survival (EFS)/overall survival (OS) estimates were analyzed by Kaplan-Meier product-limit estimator. Cox regression analysis was performed to identify prognostic factors predicting outcome in relapsed ES. Results: Salvage regimen was given to 53/108 relapsed ES patients with the rest having opted for palliation upfront. Median age of the treated patients was 19 years (range: 4-40); male:female ratio was 2.7:1. Median time to first relapse was 18.8 months (range: 2.2-91). While 41/53 patients (77%) completed salvage therapy, 6 (11.3%) progressed and 6 (11.3%) abandoned treatment. Median follow-up of the study cohort is 31 months (range: 4-81). Of the analyzable cohort (n = 47), 30 (64%) had a second relapse or progression on salvage treatment. At last follow-up, 31 patients had died (including one due to toxicity and rest due to disease) and 16 patients were alive (14 with no active disease and 2 with disease). The 4-year EFS and OS are 28% and 37%, respectively, for the entire cohort. While adolescents and young adult patients (AYA) had a better survival (p-0.041), relapsed ES patients with shorter disease-free interval (DFI) (<24 months) had a poorer survival (p-0.004). The type of relapse (local or metastatic or combined) after primary treatment did not affect outcome after salvage therapy. Conclusions: We have used a novel hybrid chemotherapy protocol using four active agents in relapsed ES, which is well tolerated and shows promising results. Older age (≥15 years) and longer DFI (>24 months) portend better survival post-relapse. In our cohort of relapsed ES, AYAs fared better than others and type of relapse after primary treatment did not affect outcome after salvage therapy.


Assuntos
Neoplasias Ósseas , Sarcoma de Ewing , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Sarcoma de Ewing/tratamento farmacológico , Adulto Jovem
15.
Acta Oncol ; 59(12): 1520-1527, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32924733

RESUMO

BACKGROUND: There are limited data on the role of chemotherapy in patients with small cell lung cancer (SCLC) and poor performance status (PS). METHODS: This was a retrospective analysis of a prospective observational study in patients with SCLC and PS 3 or 4. We recorded the initial therapy, symptom improvement, response rate, overall survival (OS), and the impact of various factors on OS. RESULTS: From June 2010 to August 2019, we enrolled 234 patients; 185 (79%) with PS 3 and 49 (21%) PS 4. Initial therapy was best supportive care (BSC) in 49 patients (21%), standard full dose chemotherapy in 31 (13%), and attenuated chemotherapy in 154 (66%). In 89% patients treated with attenuated chemotherapy, symptom-relief occurred at a median of 3 days (IQR, 1-7). Grade 3 and higher toxicities developed in 60% patients treated with initial attenuated chemotherapy, commonly hyponatremia in 39%, neutropenia in 16%, anemia in 11%, and infection in 10%. Grade 3 and higher toxicities as a result of standard chemotherapy occurred in 89% patients treated with upfront standard full dose chemotherapy compared to 69% of patients who received initial attenuated chemotherapy with subsequent treatment escalation. Overall, there were 6 (2.6%) toxic deaths. The response rate to chemotherapy was 77%. The median OS of the patients who received any chemotherapy was significantly longer at 6 months (95% CI, 4.8-7.2) compared to 1 month (95% CI, 0.4-1.6 months) in patients who were managed with BSC, p < 0.001; hazard ratio, 0.39 (95% CI, 0.27-0.56). The disease stage, lactate dehydrogenase level, and receipt of chemotherapy significantly impacted survival. CONCLUSION: Chemotherapy prolongs survival in patients with SCLC and poor PS. Administering an initial attenuated chemotherapy regimen followed by standard full-dose chemotherapy when the PS improves may lower toxicity and improve tolerance.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Resultado do Tratamento
16.
Indian J Orthop ; : 1-13, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32836361

RESUMO

With the novel coronavirus disease (COVID-19) being declared a global pandemic by the World Health Organization, the Indian healthcare sector is at the forefront to deliver optimal care. Patients with cancer especially are at serious risk for increased chances of morbidity and mortality due to their immunocompromised state. Currently there is a paucity of definitive guidelines for the management of sarcomas during the pandemic in a resource-constrained and diverse population setting like India. Health care professionals from various specialties involved in the management of sarcomas have collaborated to discuss various aspects of evidence-based sarcoma management during the COVID-19 pandemic. This article provides structured recommendations for HCP to adapt to the situation, optimize treatment protocols with judicious use of all resources while providing evidence-based treatment for sarcoma patients.

17.
Ecancermedicalscience ; 14: 1038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565891

RESUMO

Background: The use of antibiotics is known to alter the gut microbiome and it is hypothesised that the use of antibiotics may also alter the response to immune checkpoint inhibitors (ICI). As data is limited from real-world settings, we performed a retrospective audit of patients who received ICI along with concomitant antibiotics. Patients and Methods: This study is a retrospective audit of a prospectively collected the database of patients who received ICI for advanced solid tumours in any line between August 2015 and November 2018 at Tata Memorial Hospital, Mumbai, India. Antibiotic use was recorded from 2 weeks before the start of ICI and concomitantly with ICI. All statistical calculations were performed using Statistical Package for the Social Sciences (SPSS) statistical software for windows version 20.0. Results: A total of 155 patients were identified as having received ICI during the study period, out of which 70 (44%) patients received antibiotics. Median PFS in patients who received antibiotics was 1.7 months (95% CI: 1.1-2.3) as against 3.6 months (95% CI: 2.3-4.8) for patients who did not receive antibiotics (p = 0.912). Median OS in the patients who received antibiotics was 3.9 months (95% CI: 1.8-11.4) as compared to 9.2 months (95% CI: 4.2-12.3) who did not receive antibiotics p = 0.053 (HR = 1.023; 95% CI: 1.00-1.04). Among the patients who received antibiotics, median OS for patients who received ≤10 days of antibiotics was 8.8 months (95% CI: 4.2-11.2) while for patients receiving >10 days of antibiotics, it was 2.8 months (95% CI: 1.2-4.4), p = 0.025 (HR = 2.0, 95% CI: 1.1-3.7). Thirty-three (21.2% of total) patients received antibiotics during the window of 2 weeks before the start of ICI to 2 months of starting ICI. Median OS in the patients who received antibiotics in this window was 2.8 months (95% CI: 1.2-4.5) as compared to 9.2 months (95% CI: 5.2-13.1) who did not receive antibiotics p = 0.008 (HR = 1.8; 95%CI: 1.2-3.0). Conclusions: This study shows that the judicious use of antibiotics is required in patients on ICI or scheduled to be started on ICI.

18.
Cancer Med ; 9(13): 4676-4685, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32400117

RESUMO

BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Reposicionamento de Medicamentos , Glioblastoma/tratamento farmacológico , Mebendazol/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/radioterapia , Feminino , Glioblastoma/radioterapia , Humanos , Lomustina/administração & dosagem , Masculino , Dose Máxima Tolerável , Mebendazol/efeitos adversos , Adesão à Medicação , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Ondansetron/administração & dosagem , Reirradiação , Terapia de Salvação/métodos , Temozolomida/administração & dosagem
19.
Indian J Orthop ; 54(2): 215-223, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32257040

RESUMO

Background: This study aimed at evaluating the imaging findings of phosphaturic mesenchymal tumors and tumor-induced osteomalacia and assess the clinical and biochemical profiles of patients with tumor-induced osteomalacia. Materials and methods: Imaging findings in six patients with tumor-induced osteomalacia and histopathologically proven phosphaturic mesenchymal tumors were evaluated. Clinical and biochemical profiles of these patients were also assessed. Results: Along with having a characteristic biochemical profile, patients with phosphaturic mesenchymal tumors also have certain imaging findings which can aid in the diagnosis such as increased uptake on DOTA PET-CT and homogeneous post-contrast enhancement on CT and MRI. Conclusion: Patients with tumor-induced osteomalacia have characteristic symptoms, imaging and biochemical profiles. For radiologists, raising the suspicion of a phosphaturic mesenchymal tumor in patients with refractory hypophosphatemic osteomalacia as well as localizing the tumor on imaging is crucial, as complete excision of the tumor leads to resolution of the osteomalacia and the patient's clinical symptoms.

20.
Turk Patoloji Derg ; 1(1): 71-77, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149365

RESUMO

Pulmonary sarcomatoid carcinoma is rare, with limited treatment options and poor prognosis. In contrast to other non small cell lung carcinomas, not much is known about its molecular biology. In an endemic country like India, lung cancer is often masked by tuberculosis and presents in advanced stages. We report here an unusual case of pulmonary sarcomatoid carcinoma, in a young non-smoker male, who had co-existent tuberculosis masking and delaying the diagnosis of malignancy. On molecular study, the tumor showed ALK gene rearrangement, both by immunohistochemistry and fluorescence in-situ hybridization, which has been reported only twice previously. Presence of ALK gene rearrangements in sarcomatoid carcinoma has significant therapeutic implications and potential for altering the prognosis of this fatal disease. Hence we recommend performing ALK gene rearrangement analysis in all cases of sarcomatoid lung carcinomas. The report discusses the diagnostic approach and provides insight into the molecular pathogenesis of this exceedingly rare malignancy.


Assuntos
Receptores de Activinas Tipo II/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Tuberculose Pulmonar/complicações , Adulto , Carcinoma Pulmonar de Células não Pequenas/complicações , Evolução Fatal , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/complicações , Masculino
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