RESUMO
PURPOSE: Recent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited. METHODS AND MATERIALS: This prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P < .0001). The median PFS (95% confidence interval) was 11.2 months (7.6-15.9 months), and the median OS was 28.4 months (14.5-45.8 months). Survival outcomes were not significantly different for patients with brain metastases (P = .87 for PFS; P = .12 for OS) or lymph node involvement (P = .74 for PFS; P = .86 for OS). CONCLUSIONS: For patients with oligometastatic NSCLC, chemotherapy followed by consolidative radiation therapy without maintenance chemotherapy was associated with encouraging long-term outcomes.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimiorradioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Metástase Linfática , Quimioterapia de Manutenção , Masculino , Mediastino/efeitos da radiação , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Radiocirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: Outcomes data treating patients with oligometastatic (≤ 5 metastases) non-small cell lung carcinoma (NSCLC) with hypofractionated image-guided radiotherapy (HIGRT) are limited. METHODS: Consecutive oligometastatic NSCLC patients were reviewed from a prospective database. Patients were included if all active diseases were treated with HIGRT. Lesions that had received prior radiation or had radiographic/metabolic resolution after chemotherapy were not treated with HIGRT. Local control of all treated lesions, distant control, progression-free survival (PFS), overall survival (OS), and control of individual lesions (LeC) were calculated. RESULTS: Twenty-five patients with median of 2 treated oligometastatic lesions were included. Median follow-up was 14 months. Median age was 66 years. Nineteen patients received systemic therapy before HIGRT and 11 had progressive disease after their most recent systemic therapy before HIGRT. Median OS and PFS were 22.7 and 7.6 months. The 18 months local control, distant control, OS, and PFS were 66.1%, 31.7%, 52.9%, and 28.0%. Greater than two sites treated with HIGRT, nonadenocarcinoma histology, prior systemic therapy, and progression after systemic therapy were associated with worse PFS. Sixty-two individual lesions of median size 2.7 cm were treated. For extracranial lesions, median total and fraction dose were 50 and 5 Gy. Median standard equivalent dose in 2 Gy fractions for extracranial lesions was 64.6 Gy yielding 18 months LeC of 70.7%. Standard equivalent dose ≥64.6 Gy increased LeC (p = 0.04). Two patients experienced grade 3 toxicity. CONCLUSIONS: HIGRT for oligometastatic NSCLC provides durable LeC and may provide long-term PFS in some patients. Future HIGRT studies should optimize patient selection and integration with systemic therapy.
Assuntos
Adenocarcinoma/radioterapia , Carcinoma de Células Grandes/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Escamosas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia Guiada por Imagem , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: To determine the maximal tolerated biologic dose intensification of radiotherapy using fractional dose escalation with temozolomide (TMZ) chemotherapy in patients with newly diagnosed glioblastoma multiforme. METHODS AND MATERIALS: Patients with newly diagnosed glioblastoma multiforme after biopsy or resection and with adequate performance status, bone marrow, and organ function were eligible. The patients underwent postoperative intensity-modulated radiotherapy (IMRT) with concurrent and adjuvant TMZ. All patients received a total dose of 60 Gy to the surgical cavity and residual tumor, with a 5-mm margin. IMRT biologic dose intensification was achieved by escalating from 3 Gy/fraction (Level 1) to 6 Gy/fraction (Level 4) in 1-Gy increments. Concurrent TMZ was given at 75 mg/m(2)/d for 28 consecutive days. Adjuvant TMZ was given at 150-200 mg/m(2)/d for 5 days every 28 days. Dose-limiting toxicity was defined as any Common Terminology Criteria for Adverse Events, version 3, Grade 3-4 nonhematologic toxicity, excluding Grade 3 fatigue, nausea, and vomiting. A standard 3+3 Phase I design was used. RESULTS: A total of 16 patients were accrued (12 men and 4 women, median age, 69 years; range, 34-84. The median Karnofsky performance status was 80 (range, 60-90). Of the 16 patients, 3 each were treated at Levels 1 and 2, 4 at Level 3, and 6 at Level 4. All patients received IMRT and concurrent TMZ according to the protocol, except for 1 patient, who received 14 days of concurrent TMZ. The median number of adjuvant TMZ cycles was 7.5 (range, 0-12). The median survival was 16.2 months (range, 3-33). One patient experienced vision loss in the left eye 7 months after IMRT. Four patients underwent repeat surgery for suspected tumor recurrence 6-12 months after IMRT; 3 had radionecrosis. CONCLUSIONS: The maximal tolerated IMRT fraction size was not reached in our study. Our results have shown that 60 Gy IMRT delivered in 6-Gy fractions within 2 weeks with concurrent and adjuvant TMZ is tolerable in selected patients with a T(1)-weighted enhancing tumor <6 cm.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Temozolomida , Carga TumoralRESUMO
PURPOSE: To analyze the pathology, outcomes, and prognostic factors in patients with high-grade glioma undergoing reoperation after radiotherapy (RT). METHODS AND MATERIALS: Fifty-one patients with World Health Organization Grade 3-4 glioma underwent reoperation after prior RT. The median dose of prior RT was 60 Gy, and 84% received chemotherapy as part of their initial treatment. Estimation of the percentage of necrosis and recurrent tumor in each reoperation specimen was performed. Pathology was classified as RT necrosis if ≥80% of the specimen was necrotic and as tumor recurrence if ≥20% was tumor. Predictors of survival were analyzed using log-rank comparisons and Cox proportional hazards regression. RESULTS: The median interval between the completion of RT and reoperation was 6.7 months (range, 1-59 months). Pathologic analysis showed RT necrosis in 27% and recurrence in 73% of cases. Thirteen patients required a reoperation for uncontrolled symptoms. Among them, 1 patient (8%) had pathology showing RT necrosis, and 12 (92%) had tumor recurrence. Median survival after reoperation was longer for patients with RT necrosis (21.8 months vs. 7.0 months, p=0.047). In 7 patients with Grade 4 tumors treated with temozolomide-based chemoradiation with RT necrosis, median survival from diagnosis and reoperation were 30.2 months and 21.8 months, respectively. CONCLUSIONS: Patients with RT necrosis at reoperation have improved survival compared with patients with tumor recurrence. Future efforts to intensify local therapy and increase local tumor control in patients with high-grade glioma seem warranted.
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Astrocitoma/cirurgia , Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Carmustina/uso terapêutico , Colorado , Terapia Combinada/métodos , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Necrose , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Reoperação , Retratamento , Terapia de Salvação/métodos , Temozolomida , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: To present the first report of a Phase I trial evaluating concurrent and maintenance erlotinib and reirradiation in patients with recurrent or secondary primary head-and-neck cancer (HNC). METHODS AND MATERIALS: Patients with recurrent or new primary HNC with an interval of at least 6 months since prior radiation were eligible. Patients were treated in 3 sequential cohorts: Cohort I, 100 mg of erlotinib daily with reirradiation at 61.6 Gy in 28 fractions; Cohort II, 150 mg of erlotinib with 61.6 Gy in 28 fractions; and Cohort III, 150 mg of erlotinib with 66 Gy in 30 fractions. Maintenance erlotinib started immediately after reirradiation at 150 mg daily and was continued for 2 years or until disease progression or dose-limiting toxicity. Dose-limiting toxicities were defined as any Grade 4 or 5 toxicity or a toxicity-related delay in radiation therapy of greater than 7 days. RESULTS: Fourteen patients were accrued, 3 to Cohort I, 4 to Cohort II, and 7 to Cohort III. Thirteen patients were evaluable for toxicity. Median follow-up was 8.4 months overall and 15.1 months for surviving patients. One patient had a dose-limiting toxicity in Cohort III. This patient declined initial percutaneous endoscopic gastrostomy tube placement, was hospitalized with Grade 3 dysphagia and aspiration, and required a delay in radiation therapy of greater than 7 days. No Grade 4 acute toxicity was observed. Acute Grade 3 toxicity occurred in 9 of 13 patients. No erlotinib-related toxicity of Grade 3 or greater was observed during maintenance therapy. One patient had Grade 5 carotid hemorrhage 6 months after reirradiation, and another patient had Grade 3 osteoradionecrosis. CONCLUSIONS: Reirradiation (66 Gy in 2.2 Gy fractions) with concurrent and maintenance erlotinib (150 mg daily) for recurrent or new primary HNC is feasible.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Cetuximab , Terapia Combinada/métodos , Esquema de Medicação , Cloridrato de Erlotinib , Estudos de Viabilidade , Feminino , Seguimentos , Gastrostomia/métodos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Dosagem Radioterapêutica , Retratamento , Resultado do TratamentoRESUMO
PURPOSE: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. METHODS AND MATERIALS: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m(2), 1.3 mg/m(2), and 1.6 mg/m(2)/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade ≥3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for ≥2 weeks. RESULTS: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m(2). One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). CONCLUSIONS: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m(2) is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m(2).
Assuntos
Antineoplásicos/efeitos adversos , Ácidos Borônicos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Pirazinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Bortezomib , Colorado , Terapia Combinada/métodos , Diarreia/etiologia , Fracionamento da Dose de Radiação , Relação Dose-Resposta a Droga , Esquema de Medicação , Fadiga/etiologia , Feminino , Humanos , Infusões Intravenosas/métodos , Linfopenia/etiologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Náusea/etiologia , Neoplasias/diagnóstico por imagem , Neutropenia/etiologia , Cuidados Paliativos/métodos , Pirazinas/administração & dosagem , RadiografiaRESUMO
PURPOSE: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality. METHODS AND MATERIALS: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. RESULTS: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005). CONCLUSIONS: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.
Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Cardiopatias/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/radioterapia , Causas de Morte , Terapia Combinada/métodos , Feminino , Seguimentos , Cardiopatias/induzido quimicamente , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Programa de SEERRESUMO
PURPOSE: To evaluate the survival and patterns of relapse for patients with squamous cell carcinoma (SCC) of the oral tongue. PATIENTS AND METHODS: Between 1999 and 2007, 50 patients with SCC of the oral tongue were treated at the University of Colorado Denver. Of the 50 patients, 38 had newly diagnosed SCC of the oral tongue (13 with stage I-II and 25 with stage III-IV disease), and 12 presented with locally recurrent SCC. Of the 50 patients, 49 were treated with initial surgery and 1 with definitive chemoradiotherapy. Adjuvant radiotherapy or chemoradiotherapy was administered to 42 patients after surgery. Of the 13 patients with newly diagnosed stage I-II disease, 7 did not receive adjuvant therapy. The actuarial locoregional control, freedom from distant relapse, and survival were determined using the Kaplan-Meier method, and comparisons were made using the log-rank test. RESULTS: The median follow-up was 29 months (range 4 to 95) for living patients. The 2-year locoregional control and freedom from distant relapse rate was 58% and 83%, respectively. Locoregional control was particularly low among patients with stage I-II disease, for whom the 2-year locoregional control rate was only 35%. The median survival time and 2-year survival rate for all patients was 42 months and 65%, respectively. The 2-year survival rate for patients with stage I-II oral tongue cancer was 77% compared with 52% for patients with stage III-IV disease (P = .04). CONCLUSIONS: Despite aggressive therapy, patients with SCC of the oral tongue have a low rate of local tumor control and survival, particularly among those with stage I-II disease. These patients should be considered for inclusion in clinical trials evaluating novel postoperative therapies.
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Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Taxa de Sobrevida , Neoplasias da Língua/cirurgia , Neoplasias da Língua/terapiaRESUMO
PURPOSE: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. METHODS AND MATERIALS: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to score toxicity. RESULTS: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving > or =25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving > or =50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. CONCLUSION: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.
Assuntos
Intestinos/efeitos da radiação , Neoplasias da Próstata/radioterapia , Lesões por Radiação/complicações , Radioterapia de Intensidade Modulada/efeitos adversos , Bexiga Urinária/efeitos da radiação , Idoso , Antagonistas de Androgênios/uso terapêutico , Cistite/etiologia , Fracionamento da Dose de Radiação , Humanos , Irradiação Linfática/efeitos adversos , Irradiação Linfática/métodos , Masculino , Pessoa de Meia-Idade , Pelve , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/tratamento farmacológico , Radiografia , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Transtornos Urinários/etiologiaRESUMO
INTRODUCTION: The pattern of failure (POF) after first-line systemic therapy in advanced non-small cell lung cancer (NSCLC) is unknown. We evaluate the POF in this setting to estimate the potential value of consolidative stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: The records of consecutive NSCLC patients presenting to the University of Colorado, Denver (UCD) between January 2005 and June 2008 were reviewed. Patients with measurable advanced stage NSCLC who received first-line systemic therapy and follow-up at UCD were eligible. In these patients, sites of disease at maximal response were evaluated for theoretical SBRT eligibility, based on institutional criteria. All patients were followed to extracranial progression. The POF was categorized as local (L) for lesions known prior to treatment or distant (D) for new lesions. RESULTS: Among 387 consecutive lung cancer patients (all stages), 64 met the eligibility criteria and 34 were SBRT-eligible. Among all eligible patients, first extra-cranial progression was L-only in 64%, D-only in 9% and L + D in 27%. Among SBRT-eligible patients, POF was L-only in 68%, D-only in 14% and L + D in 18%. In SBRT-eligible patients, time to first progression was 3.0 months in those with L-only failure versus 5.7 month in those with any D failure (HR 0.44; 95% CI 0.22-0.90). CONCLUSIONS: The predominant POF in patients with advanced NSCLC after first-line systemic therapy is local-only. The current analysis suggests that SBRT could improve time to progression in a substantial proportion of patients. The estimated increase in time to progression using this approach would be approximately 3 months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante , Estudos Retrospectivos , Falha de TratamentoRESUMO
PURPOSE: To evaluate the efficacy and tolerability of high-dose stereotactic body radiation therapy (SBRT) for the treatment of patients with one to three lung metastases. PATIENTS AND METHODS: Patients with one to three lung metastases with cumulative maximum tumor diameter smaller than 7 cm were enrolled and treated on a multi-institutional phase I/II clinical trial in which they received SBRT delivered in 3 fractions. In phase I, the total dose was safely escalated from 48 to 60 Gy. The phase II dose was 60 Gy. The primary end point was local control. Lesions with at least 6 months of radiographic follow-up were considered assessable for local control. Secondary end points included toxicity and survival. RESULTS: Thirty-eight patients with 63 lesions were enrolled and treated at three participating institutions. Seventy-one percent had received at least one prior systemic regimen for metastatic disease and 34% had received at least two prior regimens (range, zero to five). Two patients had local recurrence after prior surgical resection. There was no grade 4 toxicity. The incidence of any grade 3 toxicity was 8% (three of 38). Symptomatic pneumonitis occurred in one patient (2.6%). Fifty lesions were assessable for local control. Median follow-up for assessable lesions was 15.4 months (range, 6 to 48 months). The median gross tumor volume was 4.2 mL (range, 0.2 to 52.3 mL). Actuarial local control at one and two years after SBRT was 100% and 96%, respectively. Local progression occurred in one patient, 13 months after SBRT. Median survival was 19 months. CONCLUSION: This multi-institutional phase I/II trial demonstrates that high-dose SBRT is safe and effective for the treatment of patients with one to three lung metastases.
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Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversosRESUMO
PURPOSE: To evaluate the efficacy and tolerability of high-dose stereotactic body radiation therapy (SBRT) for the treatment of patients with one to three hepatic metastases. PATIENTS AND METHODS: Patients with one to three hepatic lesions and maximum individual tumor diameters less than 6 cm were enrolled and treated on a multi-institutional, phase I/II clinical trial in which they received SBRT delivered in three fractions. During phase I, the total dose was safely escalated from 36 Gy to 60 Gy. The phase II dose was 60 Gy. The primary end point was local control. Lesions with at least 6 months of radiographic follow-up were considered assessable for local control. Secondary end points were toxicity and survival. RESULTS: Forty-seven patients with 63 lesions were treated with SBRT. Among them, 69% had received at least one prior systemic therapy regimen for metastatic disease (range, 0 to 5 regimens), and 45% had extrahepatic disease at study entry. Only one patient experienced grade 3 or higher toxicity (2%). Forty-nine discrete lesions were assessable for local control. Median follow-up for assessable lesions was 16 months (range, 6 to 54 months). The median maximal tumor diameter was 2.7 cm (range, 0.4 to 5.8 cm). Local progression occurred in only three lesions at a median of 7.5 months (range, 7 to 13 months) after SBRT. Actuarial in-field local control rates at one and two years after SBRT were 95% and 92%, respectively. Among lesions with maximal diameter of 3 cm or less, 2-year local control was 100%. Median survival was 20.5 months. CONCLUSION: This multi-institutional, phase I/II trial demonstrates that high-dose liver SBRT is safe and effective for the treatment of patients with one to three hepatic metastases.
Assuntos
Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversosRESUMO
PURPOSE: Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. METHODS AND MATERIALS: Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. RESULTS: Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. CONCLUSIONS: IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.
Assuntos
Braquiterapia/efeitos adversos , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Paládio , Antígeno Prostático Específico/sangue , Radioisótopos , Dosagem Radioterapêutica , Medição de RiscoRESUMO
PURPOSE: To review the outcomes of a prospective management approach using ipsilateral neck radiotherapy in the treatment of node-positive squamous cell carcinoma of the tonsil with a well-lateralized primary lesion. METHODS AND MATERIALS: Between August 2003 and June 2007, 20 patients who presented with squamous cell carcinoma of the tonsil, without involvement of the base of the tongue or midline soft palate, and with Stage N1-N2b disease were prospectively treated with radiotherapy to the primary site and ipsilateral neck. In addition, 18 patients received concurrent chemotherapy. The actuarial freedom from contralateral nodal and in-field progression was determined. Acute and late toxicity were prospectively evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, and Radiation Therapy Oncology Group criteria. RESULTS: The nodal disease was Stage N1 in 4 patients, N2a in 3 patients, and N2b in 13 patients. At a median follow-up 19 months (range, 12-40), no in-field or contralateral nodal recurrences had been observed. The 2-year freedom from distant metastasis rate was 87.4%. The actuarial 2-year disease-free and overall survival rates were both 79.5%. Late Radiation Therapy Oncology Group grade 2 xerostomia occurred in 1 patient (5%). No late Grade 3 or greater toxicity was observed. No patient was feeding tube dependent at their last follow-up visit. CONCLUSION: In carefully selected patients with node-positive, lateralized tonsillar cancer, treatment of the ipsilateral neck and primary site does not appear to increase the risk of contralateral nodal failure and reduces late morbidity compared with historical controls. Although the outcomes with ipsilateral radiotherapy in the present series were promising, these findings require longer follow-up and validation in a larger patient cohort.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Tonsilares/radioterapia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Pescoço , Estadiamento de Neoplasias , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia Conformacional/métodos , Taxa de Sobrevida , Neoplasias Tonsilares/tratamento farmacológico , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/patologia , Resultado do TratamentoRESUMO
PURPOSE: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. METHODS AND MATERIALS: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. =10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. >/=65 years), and gender as covariates. RESULTS: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. CONCLUSION: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Esofagectomia , Terapia Neoadjuvante , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Idoso , Análise de Variância , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/cirurgia , Esofagectomia/mortalidade , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/mortalidade , Programa de SEER , Análise de SobrevidaRESUMO
PURPOSE: Lung cancer screening trials depend on the selection of a sufficiently high-risk population. Because not all smokers develop cancer, we hypothesize that a history of tobacco-associated malignancy might more reliably predict for subsequent lung cancer. Because patients with early-stage bladder transitional cell carcinoma (TCC) often have a long survival, we considered whether they would constitute a suitable population for a screening study. PATIENTS AND METHODS: Patients with Ta/is/1 N0 M0 TCC of the bladder and no history of previous cancer treated surgically between 1983 and 2002 were studied using the Surveillance, Epidemiology, and End Results (SEER) database. The incidence and cancer-specific mortality of second nonurothelial solid organ cancers was determined. The standardized incidence ratio (SIR) and 15-year actuarial incidences were determined. RESULTS: From 1983 to 2002, 8300 patients meeting the inclusion criteria were entered into the SEER-9 Registry. Among them, the SIR for a second solid organ malignancy was 1.25 (95% CI, 1.18-1.32). The SIR was significantly increased for tumors of the lung (1.71), head and neck (1.32), and prostate (1.28). The 15-year incidence of and mortality from lung cancer were 8.8% and 8.6%, respectively. Among all nonurothelial second malignancies, lung cancers accounted for 32.5% of the incidence and 53.4% of cancer-specific deaths. Moreover, lung cancer accounted for 12.2% of overall deaths in these patients. CONCLUSIONS: Patients with non-muscle-invasive bladder TCC suffer a high incidence of mortality from lung cancer and might constitute a suitable population for a lung screening trial. Other tobacco-related health events might add to smoking history in identifying high-risk populations.