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1.
Clin Oncol (R Coll Radiol) ; 36(6): e137-e145, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565457

RESUMO

AIMS: Sinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. METHODS: This was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. RESULTS: The data of 27 patients were evaluated from the year 2015-2022. The median age was 42 years (IQR:30-56) and 85.2% (n = 23) were males. The ECOG-PS was 0-1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2-3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0-25.6) and 23months (95%CI:5.94-40.06) respectively. CONCLUSION: NACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.


Assuntos
Carcinossarcoma , Terapia Neoadjuvante , Neoplasias Nasais , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Estudos Retrospectivos , Índia , Adulto , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Carcinossarcoma/tratamento farmacológico , Carcinossarcoma/terapia , Carcinossarcoma/patologia , Neoplasias dos Seios Paranasais/tratamento farmacológico , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/patologia , Teratoma/tratamento farmacológico , Teratoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Quimioterapia Adjuvante/métodos
2.
Clin Oncol (R Coll Radiol) ; 36(5): 278-286, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38365518

RESUMO

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Estudos Retrospectivos , Radioterapia Adjuvante , Carcinoma de Células Escamosas/patologia , Metástase Linfática/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Estadiamento de Neoplasias
3.
Clin Oncol (R Coll Radiol) ; 36(1): e61-e71, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37953073

RESUMO

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.


Assuntos
Avaliação Geriátrica , Neoplasias , Idoso , Humanos , Pessoa de Meia-Idade , Avaliação Geriátrica/métodos , Neoplasias/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais , Comorbidade
6.
Clin Oncol (R Coll Radiol) ; 35(9): e506-e515, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37208232

RESUMO

AIMS: To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. MATERIALS AND METHODS: The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy - Colorectal questionnaire is recorded pre-treatment and at follow-up. ENDPOINTS AND STATISTICS: The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. CONCLUSION: The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Radioterapia Adjuvante , Qualidade de Vida , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias da Bexiga Urinária/cirurgia , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Eur Heart J ; 44(10): 885-898, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36660854

RESUMO

AIMS: Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored. METHODS AND RESULTS: An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype. CONCLUSION: Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.


Assuntos
Estenose da Valva Aórtica , Calcinose , Humanos , Animais , Camundongos , Estenose da Valva Aórtica/genética , Valva Aórtica/patologia , Calcinose/metabolismo , Constrição Patológica , Células Cultivadas , Fibrose
9.
Clin Radiol ; 78(3): 175-186, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36503631

RESUMO

Increased survival (due to the use of targeted therapies based on genomic profiling) has resulted in the increased incidence of brain metastasis during the course of disease, and thus, made it essential to have proper imaging guidelines in place for brain metastasis from non-small-cell lung cancer (NSCLC). Brain parenchymal metastases can have varied imaging appearances, and it is pertinent to be aware of the various molecular risk factors for brain metastasis from NSCLC along with their suggestive imaging appearances, so as to identify them early. Leptomeningeal metastasis requires additional imaging of the spine and an early cerebrospinal fluid (CSF) analysis. Differentiation of post-therapy change from recurrence on imaging has a bearing on the management, hence the need for its awareness. This article will provide in-depth literature review of the epidemiology, aetiopathogenesis, screening, detection, diagnosis, post-therapy imaging, and implications regarding the management of brain metastasis from NSCLC. In addition, we will also briefly highlight the role of artificial intelligence (AI) in brain metastasis screening.


Assuntos
Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Inteligência Artificial , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Diagnóstico por Imagem
10.
ESMO Open ; 7(4): 100518, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35797737

RESUMO

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.


Assuntos
Oncologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Ásia , Consenso , Europa (Continente) , Seguimentos , Humanos , Masculino
11.
Esophagus ; 19(4): 670-682, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35614161

RESUMO

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina , Celecoxib/uso terapêutico , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , Humanos , Metotrexato
12.
J Laryngol Otol ; 136(11): 1087-1095, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35300741

RESUMO

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.


Assuntos
Carcinoma , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Humanos , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/terapia , Estudos Retrospectivos , Resultado do Tratamento , Carcinoma/cirurgia , Carcinoma/terapia
13.
Circulation ; 145(7): 531-548, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35157519

RESUMO

BACKGROUND: Rheumatic heart valve disease (RHVD) is a leading cause of cardiovascular death in low- and middle-income countries and affects predominantly women. The underlying mechanisms of chronic valvular damage remain unexplored and regulators of sex predisposition are unknown. METHODS: Proteomics analysis of human heart valves (nondiseased aortic valves, nondiseased mitral valves [NDMVs], valves from patients with rheumatic aortic valve disease, and valves from patients with rheumatic mitral valve disease; n=30) followed by system biology analysis identified ProTα (prothymosin alpha) as a protein associated with RHVD. Histology, multiparameter flow cytometry, and enzyme-linked immunosorbent assay confirmed the expression of ProTα. In vitro experiments using peripheral mononuclear cells and valvular interstitial cells were performed using multiparameter flow cytometry and quantitative polymerase chain reaction. In silico analysis of the RHVD and Streptococcuspyogenes proteomes were used to identify mimic epitopes. RESULTS: A comparison of NDMV and nondiseased aortic valve proteomes established the baseline differences between nondiseased aortic and mitral valves. Thirteen unique proteins were enriched in NDMVs. Comparison of NDMVs versus valves from patients with rheumatic mitral valve disease and nondiseased aortic valves versus valves from patients with rheumatic aortic valve disease identified 213 proteins enriched in rheumatic valves. The expression of the 13 NDMV-enriched proteins was evaluated across the 213 proteins enriched in diseased valves, resulting in the discovery of ProTα common to valves from patients with rheumatic mitral valve disease and valves from patients with rheumatic aortic valve disease. ProTα plasma levels were significantly higher in patients with RHVD than in healthy individuals. Immunoreactive ProTα colocalized with CD8+ T cells in RHVD. Expression of ProTα and estrogen receptor alpha correlated strongly in circulating CD8+ T cells from patients with RHVD. Recombinant ProTα induced expression of the lytic proteins perforin and granzyme B by CD8+ T cells as well as higher estrogen receptor alpha expression. In addition, recombinant ProTα increased human leukocyte antigen class I levels in valvular interstitial cells. Treatment of CD8+ T cells with specific estrogen receptor alpha antagonist reduced the cytotoxic potential promoted by ProTα. In silico analysis of RHVD and Spyogenes proteomes revealed molecular mimicry between human type 1 collagen epitope and bacterial collagen-like protein, which induced CD8+ T-cell activation in vitro. CONCLUSIONS: ProTα-dependent CD8+ T-cell cytotoxicity was associated with estrogen receptor alpha activity, implicating ProTα as a potential regulator of sex predisposition in RHVD. ProTα facilitated recognition of type 1 collagen mimic epitopes by CD8+ T cells, suggesting mechanisms provoking autoimmunity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Colágeno Tipo I/metabolismo , Receptor alfa de Estrogênio/metabolismo , Doenças das Valvas Cardíacas/etiologia , Doenças das Valvas Cardíacas/metabolismo , Precursores de Proteínas/metabolismo , Timosina/análogos & derivados , Sequência de Aminoácidos , Colágeno Tipo I/química , Biologia Computacional/métodos , Suscetibilidade a Doenças , Epitopos de Linfócito T/imunologia , Doenças das Valvas Cardíacas/diagnóstico , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Modelos Biológicos , Modelos Moleculares , Ligação Proteica , Precursores de Proteínas/química , Precursores de Proteínas/genética , Proteoma , Proteômica/métodos , Cardiopatia Reumática/diagnóstico , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/metabolismo , Relação Estrutura-Atividade , Timosina/química , Timosina/genética , Timosina/metabolismo
14.
Clin Oncol (R Coll Radiol) ; 34(4): 220-229, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34872822

RESUMO

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.


Assuntos
Neoplasias Esofágicas , Radioterapia Guiada por Imagem , Neoplasias Esofágicas/radioterapia , Humanos , Preservação de Órgãos , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia Guiada por Imagem/métodos
15.
Clin Oncol (R Coll Radiol) ; 34(3): 172-178, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732295

RESUMO

AIMS: Due to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. PATIENTS AND METHODS: All consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan-Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). RESULTS: Of 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3-4], P = 0.027 and 2.2 [1.3-4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5-5.5], P < 0.001; multimodality: 3.1 [1.6-6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4-0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07-1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1-1], P = 0.05). CONCLUSION: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.


Assuntos
Neoplasias Penianas , Quimioterapia Adjuvante , Terapia Combinada , Humanos , Linfonodos/patologia , Masculino , Estadiamento de Neoplasias , Pelve/patologia , Neoplasias Penianas/patologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos
16.
Clin Oncol (R Coll Radiol) ; 33(7): e315-e321, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33608206

RESUMO

AIMS: There is a lack of consensus regarding the management of post-chemotherapy residual mass in classical seminoma. The use of fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) may aid the detection of residual masses harbouring viable disease and help to tailor therapy. The aim of this study was to evaluate if PET-CT could identify patients who will benefit from locoregional radiotherapy. MATERIALS AND METHODS: This ethics-approved study included patients with advanced classical seminoma primarily treated with standard platinum-based first-line chemotherapy. Patients were either observed or given adjuvant radiotherapy based on the clinician's preference and followed up. For this study, patients were stratified into two groups based on FDG PET-CT residual nodal maximum standardised uptake value (SUVmax): low risk (SUVmax <3) and high risk (SUVmax ≥3). Further subgroup analysis was carried out for patients with residual nodal size ≥3 cm and SUVmax ≥3, and this was considered as the very high risk group. The diagnostic accuracy of FDG PET-CT was assessed and survival was compared between the different groups. RESULTS: Sixty-nine patients were included in the study: 48 patients were observed and 21 received radiotherapy. The low and high risk groups contained 50.7% and 49.3% of the patients, respectively. The very high risk subgroup had 24 patients. At a median follow-up of 44 months, locoregional failures in the radiotherapy and observation cohorts were 0% and 30% (P = 0.059) in the very high risk subgroup and 5.8% and 29.4% (P = 0.078) in the high risk group. The positive predictive value for the very high risk and high risk groups was 30% and 17.1%, respectively. The benefit of locoregional control failed to translate into overall survival benefit. CONCLUSION: A tailored, FDG PET-based risk-adapted treatment approach can refine the management of post-chemotherapy residual masses in seminoma. In this study, with the largest cohort of advanced seminoma patients treated with radiotherapy reported to date, radiotherapy seems to benefit patients with post-chemotherapy residual mass SUVmax ≥3.


Assuntos
Seminoma , Neoplasias Testiculares , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Seminoma/diagnóstico por imagem , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia
18.
Sci Rep ; 11(1): 2055, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479392

RESUMO

The repeatability and reproducibility of radiomic features extracted from CT scans need to be investigated to evaluate the temporal stability of imaging features with respect to a controlled scenario (test-retest), as well as their dependence on acquisition parameters such as slice thickness, or tube current. Only robust and stable features should be used in prognostication/prediction models to improve generalizability across multiple institutions. In this study, we investigated the repeatability and reproducibility of radiomic features with respect to three different scanners, variable slice thickness, tube current, and use of intravenous (IV) contrast medium, combining phantom studies and human subjects with non-small cell lung cancer. In all, half of the radiomic features showed good repeatability (ICC > 0.9) independent of scanner model. Within acquisition protocols, changes in slice thickness was associated with poorer reproducibility compared to the use of IV contrast. Broad feature classes exhibit different behaviors, with only few features appearing to be the most stable. 108 features presented both good repeatability and reproducibility in all the experiments, most of them being wavelet and Laplacian of Gaussian features.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Simulação por Computador , Feminino , Humanos , Imageamento por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas/normas , Reprodutibilidade dos Testes
19.
Cancer Treat Res Commun ; 26: 100269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33338859

RESUMO

In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Neoplasias de Cabeça e Pescoço/terapia , Equipe de Assistência ao Paciente/organização & administração , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Antineoplásicos Imunológicos/uso terapêutico , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Quimiorradioterapia Adjuvante/tendências , Intervalo Livre de Doença , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Índia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de Sobrevida
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