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The association between HRQOL metrics and survival has not been studied in early stage non-small-cell lung cancer (NSCLC) patients undergoing SBRT. The cohort was derived via a post-hoc analysis of a prospective randomized clinical trial examining definitive SBRT for peripheral, early-stage NSCLC with a single or multi-fraction regimen. Patients completed HRQOL questionnaires prior to and 3 months after treatment. Using principal component analysis (PCA), changes in each HRQOL scale following treatment were reduced to two eigenvectors, PC1 and PC2. Cox regression was employed to analyze associations with survival-based endpoints. A total of 70 patients (median age 75.6 years; median follow-up 41.1 months) were studied. HRQOL and symptom comparisons at baseline and 3 months were vastly unchanged except for improved coughing (p = 0.02) and pain in the chest at 3 months (p = 0.033). PC1 and PC2 explained 21% and 9% of variance, respectively. When adjusting for covariates, PC1 was significantly correlated with progression-free (PFS) (HR = 0.78, 95% CI 0.67-0.92, p = 0.003) and overall survival (OS) (HR = 0.76, 95% CI 0.46, p = 0.041). Changes in global health status, functional HRQOL performance, and/or symptom burden as described by PC1 values are significantly associated with PFS and OS. The PC1 quartile may facilitate the identification of at-risk patients for additional interventions.
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BACKGROUND: Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS: The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS: Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P<0.05). These factors were incorporated into a multivariate Cox regression model that demonstrated female sex (P=0.004, hazard ratio [HR]=0.68), KPS (P<0.001, HR=2.0), and prior lung cancer (P=0.049, HR=0.7) to be significantly associated with OS. A similar approach found only gender (P=0.017, HR=0.64) and tumor stage (P=0.02, HR=1.7) to correlate with relapse-free survival. To support the Cox regression analysis, propensity score matching was performed using gender, age, KPS, tumor stage, history of heart disease, and anticoagulation use. Kaplan-Meier survival analysis within the matched pairs found prior lung cancer to be associated with improved OS (P=0.011), but not relapse-free survival (P=0.44). CONCLUSIONS: Compared with initial lung cancer SBRT inoperable cases, ablative radiotherapy for new primaries was associated with improved OS. Physicians should not be dissuaded from offering SBRT to such patients.
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Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Análisis por Apareamiento , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
PURPOSE: Stereotactic body radiation therapy for early stage non-small cell lung cancer is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events thoracic grade 3 or higher adverse events (AEs) of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2). METHODS AND MATERIALS: This was a randomized multi-institutional, phase 2, 2-arm clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 non-small cell lung cancer were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was Common Terminology Criteria for Adverse Events thoracic grade 3 or higher AEs. Secondary endpoints were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life. RESULTS: Between September 2008 and April 2015, 98 patients were randomized. Median follow-up was 53.8 months. Ten patients were lost to follow-up, 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no grade 4 or 5 AEs. There were no differences in LC, PFS, or OS (P = .68, .86, and .94, respectively). Arm 1 reported better social functioning (P = .006) with less dyspnea (P = .016) in follow-up at 6 months. CONCLUSIONS: This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, LC, PFS, and OS. Quality of life measures of social functioning and dyspnea favored single-fraction SBRT.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Anciano , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Perdida de Seguimiento , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Supervivencia sin Progresión , Calidad de Vida , Dosificación Radioterapéutica , Radioterapia Guiada por Imagen , Criterios de Evaluación de Respuesta en Tumores Sólidos , Resultado del TratamientoRESUMEN
Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.
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BACKGROUND: Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS: Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS: Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS: In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/radioterapia , Radiocirugia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Imagen por Resonancia Magnética , Masculino , Estadificación de Neoplasias , Evaluación del Resultado de la Atención al Paciente , Tomografía Computarizada por Tomografía de Emisión de Positrones , Cuidados Posoperatorios , Radiocirugia/métodos , RecurrenciaRESUMEN
PURPOSE: To evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Peripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. RESULTS: A total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. CONCLUSIONS: No statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Estudios de Cohortes , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dosificación Radioterapéutica , Análisis de SupervivenciaRESUMEN
BACKGROUND: To compare the clinical outcomes of patients with early-stage non-small-cell lung cancer (NSCLC) who had undergone either single-fraction (SF) or three-fraction (TF) stereotactic body radiation therapy (SBRT) at a single institution during over 8-year period. PATIENTS AND METHODS: Patients with peripherally located early-stage NSCLC who had undergone SBRT from February 2007 to November 2015 were included in the present study. SBRT was delivered without heterogeneity correction. Data were retrospectively reviewed and collected in an institutional review board-approved database. R software (version 3.3.2) was used for statistical analysis. RESULTS: Of 159 total lung tumors, 65 lesions received 30 Gy (median, 30 Gy) in 1 fraction, and 94 lesions received 48 to 60 Gy (median, 60 Gy) in 3 fractions. Patients with a Karnofsky performance status < 80 were more common in the SF-SBRT cohort (P = .050). After a median follow-up of 22.2 and 26.2 months for the SF-SBRT and TF-SBRT cohorts, respectively (P = .29), no statistically significant difference was found in overall survival (P = .86), progression-free survival (P = .95), local failure (P = .95), nodal failure (P = .91), and distant failure (P = .49) at 24 months. At 1 and 2 years, the overall survival rates were 86.1% and 63.2% for the SF-SBRT cohort and 80.8% and 61.6% for the TF-SBRT cohort, respectively. At 1 and 2 years, the local control rates were 95.1% and 87.8% for the SF-SBRT cohort and 92.7% and 86.2% for the TF-SBRT cohort, respectively. Both regimens were well tolerated. CONCLUSION: Despite more patients with poor performance status in the SF-SBRT cohort, the SF- and TF-SBRT regimens showed no differences in clinical outcomes. SF-SBRT is now our standard approach.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Fraccionamiento de la Dosis de Radiación , Neoplasias Pulmonares/radioterapia , Pulmón/patología , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: To evaluate differences in outcomes of early-stage peripheral non-small-cell lung cancer (NSCLC) treated with either 3- or 5-fraction stereotactic body radiotherapy (SBRT) at 2 institutions. PATIENTS AND METHODS: Patients diagnosed with peripherally located early-stage NSCLC who received either a median dose of 60 Gy (interquartile range [IQR], 60-60, biologically effective dose, 151-151) in 3 fractions or a median dose of 50 Gy (IQR, 50-50, biologically effective dose, 94-94) in 5 fractions were included in this study. All data were retrospectively collected and reviewed in an institutional review board-approved database. RESULTS: A total of 192 lesions in 192 patients were identified: 94 received 3-fraction SBRT and 98 received 5-fraction SBRT. Patients in the 5-fraction cohort had significantly smaller tumors (P = .0021). Larger tumor size was associated with worse overall survival (hazard ratio, 1.40, P = .0013) for all patients. A single grade 3 toxicity was reported in each cohort. A propensity score-matched cohort of 94 patients was constructed with a median follow-up of 29.3 months (IQR, 17.3-44.6) for the 3-fraction cohort and 31.0 months (IQR, 17.0-48.5) for the 5-fraction cohort (P = .84). There were no statistically significant differences between these 2 cohorts in overall survival (P = .33), progression-free survival (P = .40), local failure (P = .86), and nodal or distant failure (P = .57) at 2 years. CONCLUSION: The 3- and 5-fraction SBRT regimens for early-stage peripheral NSCLC had comparable clinical outcomes. Both regimens were well tolerated. A large tumor size was an adverse prognostic factor for worse survival.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Supervivencia sin Progresión , Puntaje de Propensión , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Resultado del TratamientoRESUMEN
BACKGROUND: Stereotactic body radiation therapy (SBRT) is a treatment option for patients with early-stage non-small cell lung cancer who are medically inoperable or decline surgery. Here we compare the outcome of patients with centrally located lung tumours who underwent either single fraction (SF)- or five-fraction (FF-) SBRT at a single institution over 5 years. METHODS: Between January 2009 and October 2014, patients with centrally located lung tumours who underwent SBRT were included in this study. Data were retrospectively collected using an institutional review board-approved database. For analysis, the Kaplan-Meier method and competing risks method were used. RESULTS: In total, 11 patients received 26-30 Gy in 1 fraction, whereas 31 patients received 50-60 Gy (median 55 Gy) in 5 fractions. After a median follow-up of 12 months for SF-SBRT and 17 months for FF-SBRT groups (p = 0.64), 1-year overall survival rates were 82 and 87%, respectively. SF- and FF-SBRT groups showed no significant difference in grade 3+ toxicity (p = 0·28). The only grade 4 toxicity (n = 1) was reported in the SF-SBRT group. All toxicities occurred >12 months after the SBRT. CONCLUSIONS: SF- and FF-SBRT have comparable overall survival. SF-SBRT may have some utility for patients unable to have multi-fraction SBRT.