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1.
Int J Radiat Oncol Biol Phys ; 118(1): 107-114, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37598723

RESUMO

PURPOSE: NRG/Radiation Therapy Oncology Group 0848 is a 2-step randomized trial to evaluate the benefit of the addition of concurrent fluoropyrimidine and radiation therapy (RT) after adjuvant chemotherapy (second step) for patients with resected pancreatic head adenocarcinoma. Real-time quality assurance (QA) was performed on each patient who underwent RT. This analysis aims to evaluate adherence to protocol-specified contouring and treatment planning and to report the types and frequencies of deviations requiring revisions. METHODS AND MATERIALS: In addition to a web-based contouring atlas, the protocol outlined step-by-step instructions for generating the clinical treatment volume through the creation of specific regions of interest. The planning target volume was a uniform 0.5 cm clinical treatment volume expansion. One of 2 radiation oncology study chairs independently reviewed each plan. Plans with unacceptable deviations were returned for revision and resubmitted until approved. Treatment started after final approval of the RT plan. RESULTS: From 2014 to 2018, 354 patients were enrolled in the second randomization. Of these, 160 patients received RT and were included in the QA analysis. Resubmissions were more common for patients planned with 3-dimensional conformal RT (43%) than with intensity modulated RT (31%). In total, at least 1 resubmission of the treatment plan was required for 33% of patients. Among patients requiring resubmission, most only needed 1 resubmission (87%). The most common reasons for resubmission were unacceptable deviations with respect to the preoperative gross target volume (60.7%) and the pancreaticojejunostomy (47.5%). CONCLUSION: One-third of patients required resubmission to meet protocol compliance criteria, demonstrating the continued need for expending resources on real-time, pretreatment QA in trials evaluating the use of RT, particularly for pancreas cancer. Rigorous QA is critically important for clinical trials involving RT to ensure that the true effect of RT is assessed. Moreover, RT QA serves as an educational process through providing feedback from specialists to practicing radiation oncologists on best practices.


Assuntos
Radioterapia (Especialidade) , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Neoplasias Pancreáticas
2.
Neuro Oncol ; 23(7): 1125-1138, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33515019

RESUMO

BACKGROUND: Results of NRG Oncology RTOG 0825 reported adding bevacizumab to standard chemoradiation did not significantly improve survival endpoints and resulted in greater decline in neurocognitive function (NCF) and patient-reported outcomes (PRO) over time in bevacizumab-treated patients. The present report provides additional results of patient-centered outcomes over time and their prognostic association with survival endpoints. METHODS: NCF tests, MD Anderson Symptom Inventory - Brain Tumor Module (MDASI-BT), and European Organization for Research and Treatment of Cancer (EORTC) quality of life (QOL) questionnaire with brain cancer module (QLQ-C30/BN20) were completed in a subset of progression-free patients at baseline and longitudinally. The prognostic value of baseline and early changes in NCF and PROs and differences between treatments from baseline to follow-up assessments were evaluated. RESULTS: A total of 508 randomized patients participated. Baseline/early changes in NCF and PROs were prognostic for OS and PFS. No between-arm differences in time to deterioration were found. At week 6, patients treated with bevacizumab evidenced greater improvement on NCF tests of executive function and the MDASI-BT Cognitive Function scale, but simultaneously reported greater decline on the EORTC Cognitive Function Scale. At later time points (weeks 22, 34, and 46), patients treated with bevacizumab had greater worsening on NCF tests as well as PRO measures of cognitive, communication, social function, motor symptoms, general symptoms, and interference. CONCLUSION: The collection of patient-centered clinical outcome assessments in this phase III trial revealed greater deterioration in NCF, symptoms, and QOL in patients treated with bevacizumab. Baseline and early change in NCF and PROs were prognostic for survival endpoints.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Quimiorradioterapia , Glioblastoma/tratamento farmacológico , Humanos , Qualidade de Vida
3.
Adv Radiat Oncol ; 6(1): 100579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33083637

RESUMO

PURPOSE: This study aimed to report our initial experience with weekly tele-video "virtual" on-treatment visits (vOTVs), describe the logistics of implementation, report the results of patient and physician surveys, and discuss the barriers, limitations, and benefits of vOTVs during the COVID-19 pandemic. METHODS AND MATERIALS: vOTVs were piloted at 2 centers and within 1 week were expanded to 4 additional centers. Patients participating in vOTVs were surveyed about their satisfaction with vOTVs, the quality of vOTVs, and confidence in their physician's ability to manage their care through vOTVs, as well as their support of and preferences related to vOTVs. Participating physicians were surveyed about their comfort and satisfaction with vOTVs. Medical directors at nonparticipating centers within our network were surveyed regarding their reasoning for not using vOTVs. RESULTS: In week 1, 72 of 81 patients between 2 pilot centers were seen using vOTVs. In week 2, 189 of 211 patients were seen using vOTVs at 6 centers. Patient satisfaction with and confidence in their physician's ability to address their concerns through the vOTV was high at 4.75 on a 5-point scale. Patients were overall very supportive (4.67) and found the quality of the visits to be as good as or better than their prior in-person weekly on-treatment visit (3.75). Physicians participating in the vOTVs felt very comfortable in their ability to manage patients through this platform (5.0) and on average did not report any difference in terms of efficiency of visits (3.0). CONCLUSIONS: vOTVs were easy to implement and well received by patients and participating physicians. Our experience suggests that vOTVs can be implemented rapidly using available technology and with a high degree of patient and physician satisfaction during this pandemic with similar efficiency to in-person on-treatment visits.

4.
Neurosurgery ; 84(1): 66-76, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29618054

RESUMO

BACKGROUND: The influence of subtotal resection (STR) on neurocognitive function (NCF), quality of life, and symptom burden in glioblastoma is unknown. If bevacizumab preferentially benefits patients with STR is unknown. OBJECTIVE: To examine these uncertainties. METHODS: NCF and patient reported outcomes (PRO) were prospectively collected in NRG Oncology RTOG 0525 and 0825. Changes in NCF and PRO measures from baseline to prespecified times were examined by Wilcoxon test, and mixed effects longitudinal modeling, to assess differences between patients who received STR vs gross-total resection. Changes were also compared among STR patients on 0825 receiving placebo vs bevacizumab to assess for a preferential therapeutic effect. Overall survival between STR and gross-total resection patients was compared using the Kaplan-Meier method. RESULTS: A total of 427 patients were eligible with STR present in 37%. At baseline, patients with STR had worse NCF, worse MD Anderson Symptom Inventory Brain Tumor Neurological Factor ratings (P = .004), and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (P = .002). Longitudinal multivariate analysis associated STR with worse NCF (Hopkins Verbal Learning Test-Revised Delayed Recognition [P = .048], Trail Making Test Part A [P = .035], and Controlled Oral Word Association [P = .049]). One hundred eighty-three STR patients from 0825 were analyzed (89 bevacizumab, 94 placebo); bevacizumab failed to demonstrate improvement in select NCF or PRO measures. CONCLUSION: STR patients had worse NCF and PROs before therapy. During adjuvant therapy, STR patients had worse objective NCF, despite accounting for tumor location. STR did not result in a detriment to OS. The addition of bevacizumab did not preferentially improve PRO or NCF outcomes in STR patients.


Assuntos
Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/cirurgia , Glioblastoma/psicologia , Glioblastoma/cirurgia , Neoplasia Residual/psicologia , Neoplasia Residual/cirurgia , Procedimentos Neurocirúrgicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/tratamento farmacológico , Qualidade de Vida , Reconhecimento Psicológico , Autorrelato , Teste de Sequência Alfanumérica , Resultado do Tratamento , Aprendizagem Verbal , Testes de Associação de Palavras , Adulto Jovem
5.
JAMA Oncol ; 3(11): 1520-1528, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28687830

RESUMO

IMPORTANCE: The role of epidermal growth factor receptor (EGFR) inhibition in chemoradiation strategies in the nonoperative treatment of patients with esophageal cancer remains uncertain. OBJECTIVE: To evaluate the benefit of cetuximab added to concurrent chemoradiation therapy for patients undergoing nonoperative treatment of esophageal carcinoma. DESIGN, SETTING, AND PARTICIPANTS: A National Cancer Institute (NCI) sponsored, multicenter, phase 3, randomized clinical trial open to patients with biopsy-proven carcinoma of the esophagus. The study accrued 344 patients from 2008 to 2013. INTERVENTIONS: Patients were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation of 50.4 Gy/1.8 Gy fractions with or without weekly cetuximab (400 mg/m2 on day 1 then 250 mg/m2 weekly). MAIN OUTCOMES AND MEASURES: Overall survival (OS) was the primary endpoint, with a study designed to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided α = .025. RESULTS: Between June 30, 2008, and February 8, 2013, 344 patients were enrolled. This analysis used all data received at NRG Oncology through April 12, 2015. Sixteen patients were ineligible, resulting in 328 evaluable patients, 159 in the experimental arm and 169 in the control arm. Patients were well matched between the treatment arms for patient and tumor characteristics: 263 (80%) with T3 or T4 disease, 215 (66%) N1, and 62 (19%) with celiac nodal involvement. Incidence of grade 3, 4, or 5 treatment-related adverse events at any time was 71 (46%), 35 (23%), or 6 (4%) in the experimental arm and 83 (50%), 28 (17%), or 2 (1%) in the control arm, respectively. A clinical complete response (cCR) rate of 81 (56%) was observed in the experimental arm vs 92 (58%) in the control arm (Fisher exact test, P = .66). No differences were seen in cCR between treatment arms for either histology (adenocarcinoma or squamous cell). Median follow-up for all patients was 18.6 months. The 24- and 36-month local failure for the experimental arm was 47% (95% CI, 38%-57%) and 49% (95% CI, 40%-59%) vs 49% (95% CI, 41%-58%) and 49% (95% CI, 41%-58%) for the control arm (HR, 0.92; 95% CI, 0.66-1.28; P = .65). The 24- and 36-month OS rates for the experimental arm were 45% (95% CI, 37%-53%) and 34% (95% CI, 26%-41%) vs 44% (95% CI, 36%-51%) and 28% (95% CI, 21%-35%) for the control arm (HR, 0.90; 95% CI, 0.70-1.16; P = .47). CONCLUSIONS AND RELEVANCE: The addition of cetuximab to concurrent chemoradiation did not improve OS. These phase 3 trial results point to little benefit to current EGFR-targeted agents in an unselected patient population, and highlight the need for predictive biomarkers in the treatment of esophageal cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00655876.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/terapia , Cetuximab/administração & dosagem , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Neoplasias Esofágicas/terapia , Paclitaxel/administração & dosagem , Adenocarcinoma/enzimologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cetuximab/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/efeitos adversos , Fracionamento da Dose de Radiação , Esquema de Medicação , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Modelos de Riscos Proporcionais , Fatores de Tempo , Resultado do Tratamento
6.
Int J Radiat Oncol Biol Phys ; 98(2): 409-418, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28463161

RESUMO

PURPOSE: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS AND MATERIALS: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. RESULTS: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." CONCLUSIONS: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between visits, and by using central compliance monitoring. These approaches are being incorporated into ongoing studies.


Assuntos
Quimiorradioterapia/efeitos adversos , Esofagite/complicações , Neoplasias Pulmonares/terapia , Microcomputadores/estatística & dados numéricos , Dor/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Autorrelato/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Apiterapia/métodos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Estudos de Viabilidade , Feminino , Mel , Humanos , Internet , Masculino , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Avaliação de Sintomas/estatística & dados numéricos , Fatores de Tempo , Estados Unidos
7.
Int J Radiat Oncol Biol Phys ; 97(4): 786-796, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28244415

RESUMO

PURPOSE: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. METHODS: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. RESULTS: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. CONCLUSION: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.


Assuntos
Quimiorradioterapia/efeitos adversos , Dietoterapia/métodos , Esofagite/prevenção & controle , Mel , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/prevenção & controle , Idoso , Esofagite/etiologia , Feminino , Humanos , Leptospermum , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Resultado do Tratamento
8.
Cancer ; 123(13): 2489-2496, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28323339

RESUMO

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.


Assuntos
Adenocarcinoma/terapia , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Nitrilas/uso terapêutico , Prostatectomia , Neoplasias da Próstata/terapia , Taxoides/uso terapêutico , Compostos de Tosil/uso terapêutico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Intervalo Livre de Doença , Docetaxel , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Radioterapia Conformacional , Radioterapia de Intensidade Modulada
9.
Int J Radiat Oncol Biol Phys ; 97(3): 554-562, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28126304

RESUMO

PURPOSE: To measure co-expression of EGFR and Ki67 proteins in pretreatment tumor biopsies of anal cancer patients enrolled on NRG Oncology RTOG 9811, a phase III trial comparing 5-fluorouracil/mitomycin-C/radiation therapy (Arm A) versus 5-fluorouracil/cisplatin/radiation therapy (Arm B), and to correlate expression with clinical outcome. METHODS AND MATERIALS: EGFR and Ki67 co-expression was measured after constructing a tissue microarray using fluorescence immunohistochemistry and automated quantitative image analysis. The Ki67 score within EGFR high versus low areas (Ki67ratio in EGFRhigh:low) in each tumor core was analyzed at the median, quartiles, and as a continuous variable. Associations between the tumor markers and clinical endpoints (overall and disease-free survival, locoregional and colostomy failure, and distant metastases) were explored. RESULTS: A total of 282 pretreatment tumors were analyzed from NRG Oncology RTOG 9811. Of evaluated specimens, 183 (65%, n=89, Arm A; n=94, Arm B) were eligible and analyzable. There were no significant differences in baseline characteristics or outcomes between analyzable and unanalyzable patient cases. Median follow-up was 6.0 years. On multivariate analysis, after adjusting for gender, patients with Ki67ratio in EGFRhigh:low ≥median had worse overall survival (hazard ratio 2.41, 95% confidence interval 1.38-4.19, P=.0019). After adjusting for N stage and largest tumor dimension, patients with Ki67ratio in EGFRhigh:low ≥ median had a higher risk of a disease-free failure (hazard ratio 1.85, 95% confidence interval 1.18-2.92, P=.0078). Technical validation with an independent anal cancer patient cohort was performed and shows a very similar biomarker score distribution. CONCLUSIONS: High Ki67ratio in EGFRhigh:low is associated with worse clinical outcome in this subset of patients with anal cancer treated with chemoradiation on NRG Oncology RTOG 9811. Evaluation within a clinical trial will be required to determine whether patients with these tumor characteristics may specifically benefit from an EGFR-targeted therapeutic agent.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/metabolismo , Neoplasias do Ânus/terapia , Quimiorradioterapia/métodos , Receptores ErbB/metabolismo , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Prognóstico , Fatores Sexuais , Falha de Tratamento , Resultado do Tratamento
10.
Urol Oncol ; 34(10): 430.e1-7, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27381895

RESUMO

INTRODUCTION: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively. MATERIALS AND METHODS: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.4Gy on RTOG 94-08 and 371 men receiving 64.8Gy to the prostatic fossa on RTOG 96-01. Acute and late urinary toxicity were scored prospectively by RTOG scales. Chi-square test/logistic regression and cumulative incidence approach/Fine-Gray regression model were used for analyses of acute and late toxicity, respectively. RESULTS: Grade≥2 acute urinary toxicity was significantly higher after primary prostatic radiation compared with postprostatectomy radiation (30.8% vs. 14.0%; P<0.001), but acute grade≥3 toxicity did not differ (3.8% vs. 2.7%; P = 0.54). After adjusting for age, primary radiation resulted in significantly higher grade≥2 acute urinary toxicity (odds ratio = 3.72; 95% CI: 1.65-8.37; P = 0.02). With median follow-up of 7.1 years, late urinary toxicity was not significantly different with primary vs. postprostatectomy radiation (5-year grade≥2: 16.7% vs. 18.3%; P = 0.65; grade≥3: 6.0% vs. 3.3%; P = 0.24). CONCLUSIONS: Primary radiation to an intact prostate resulted in higher grade≥2 acute urinary toxicity than radiation to the prostatic fossa, with no difference in late urinary toxicity. Thus, a proportion of acute urinary toxicity in men with an intact prostate may be attributable to inflammation of the prostatic gland or urethra.


Assuntos
Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Doenças Urológicas/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/efeitos da radiação , Prostatectomia , Neoplasias da Próstata/cirurgia , Índice de Gravidade de Doença , Fatores de Tempo , Uretra/efeitos da radiação
12.
Int J Radiat Oncol Biol Phys ; 83(1): 164-71, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22000749

RESUMO

PURPOSE: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. METHODS AND MATERIALS: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. RESULTS: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. CONCLUSIONS: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores/análise , Quimiorradioterapia/métodos , Reparo do DNA , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/análise , Terapia Neoadjuvante/métodos , Proteínas Nucleares/análise , Adenocarcinoma/genética , Adenocarcinoma/terapia , Idoso , Análise de Variância , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Proteínas de Ligação a DNA/análise , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/análise , Masculino , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteínas de Neoplasias/análise , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/análise , Cuidados Pré-Operatórios , Prognóstico , Análise Serial de Proteínas/métodos , Proteínas Serina-Treonina Quinases/análise
13.
Int J Radiat Oncol Biol Phys ; 65(4): 1120-8, 2006 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-16730135

RESUMO

PURPOSE: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. PATIENTS AND METHODS: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. RESULTS: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n=81) or PFT-R (n=83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). CONCLUSIONS: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Esquema de Medicação , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos
14.
Clin Lung Cancer ; 4(6): 339-46, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-14599300

RESUMO

Multiple studies have confirmed the value of radiation therapy in limited-stage small-cell lung cancer. The appropriate dose of radiation and the optimal fractionation scheme, however, remain controversial. This article will examine the history of radiation therapy in the management of small-cell lung cancer. It will review the rationale for the various approaches to radiation dose intensification, and review the results of important trials investigating the issue of radiation dose in the management of this disease. Survival outcomes and toxicity of various approaches to radiation dose intensification, including dose escalation and hyperfractionation, will be assessed. The implications of advancements in technology will be examined, and the optimal design of future trials will be discussed.

15.
Int J Radiat Oncol Biol Phys ; 57(3): 701-8, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14529774

RESUMO

PURPOSE: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients treated with > or =50 Gy of radiation at Massachusetts General Hospital (MGH) between 1987 and 2000 and to assess for evidence of a continuation of a radiation dose response. METHODS AND MATERIALS: The MGH cancer registry was searched for SCLC patients treated with radiotherapy between 1987 and 2000. Records of LS-SCLC patients treated with curative intent and radiation doses > or =50 Gy at MGH were reviewed. Surgical patients were excluded. RESULTS: Eighty-four LS-SCLC patients were treated with radiotherapy at MGH between 1987 and 2000. Of the 84 patients, 54 (64%) met the inclusion criteria; 30 patients (56%) in this study died, and 4 (7%) were lost to follow-up. The median follow-up of the surviving patients was 42 months. The median overall survival was 29 months. The 2- and 5-year survival rate was 64% and 47%, respectively. The local control rate at 3 years was 78%. CONCLUSION: The overall survival, local control, and disease-free survival rates for LS-SCLC patients treated with > or =50 Gy of radiation compare favorably with historical data. These findings suggest a continuation of the radiation dose-response curve in LS-SCLC. This further supports the need for appropriately powered, Phase III, prospective randomized trials in radiation dose escalation or radiation dose intensification for LS-SCLC.


Assuntos
Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Lesões por Radiação/etiologia , Lesões por Radiação/mortalidade , Dosagem Radioterapêutica , Falha de Tratamento
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