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BACKGROUND: We sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC). PATIENTS AND METHODS: Subjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method. RESULTS: Pretreatment TLC was 1.86 × 103/µL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030). CONCLUSIONS: Baseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.
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Plaquetas/patología , Neoplasias Pulmonares/diagnóstico , Linfocitos/patología , Neutrófilos/patología , Carcinoma Pulmonar de Células Pequeñas/diagnóstico , Anciano , Biomarcadores de Tumor , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Recuento de Linfocitos , Linfopenia , Masculino , Persona de Mediana Edad , Pronóstico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Análisis de SupervivenciaRESUMEN
BACKGROUND: Small cell lung cancer (SCLC) can recur in the brain after whole-brain irradiation (WBI). We documented outcomes after treatment of such recurrences and sought predictors of local control and overall survival (OS). MATERIALS AND METHODS: Eighty-five patients with SCLC and brain recurrence after prophylactic or therapeutic WBI in 1998-2015 were identified and data were extracted from the medical records. Survival was estimated with the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards modeling was used to identify factors associated with OS or further brain progression. RESULTS: Brain recurrence was treated by stereotactic radiosurgery (SRS) in 33 patients (39%), repeat WBI in 14 (16%), chemotherapy-only in 16 (19%), and observation in 22 (26%). Median OS time after brain recurrence (OSrec) was 4.3 months for all patients; 6-month OSrec rates were 58% after SRS, 21% after repeat WBI, 50% after chemotherapy-only, and 5% after observation (P < 0.001). Inferior OSrec was associated with poor performance status (ECOG score ≥ 3) and uncontrolled extracranial disease. Superior OSrec was associated with receipt of ≥4 chemotherapy cycles before brain recurrence and receipt of chemotherapy, SRS, or repeat WBI afterward. Receipt of chemotherapy after brain recurrence correlated with brain progression. CONCLUSIONS: Some patients with brain recurrence after WBI for SCLC can survive for extended periods with appropriate intervention, especially those with adequate performance status or controlled extracranial disease.
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Neoplasias Encefálicas/mortalidad , Irradiación Craneana/mortalidad , Neoplasias Pulmonares/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Reirradiación/mortalidad , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: A meta-analysis of sociodemographic variables and their association with late (>180 days from start of radiation therapy[RT]) bowel, bladder, and clustered bowel and bladder toxicities was conducted in patients with high-risk (clinical stages T2c-T4b or Gleason score 8-10 or prostate-specific antigen level >20) prostate cancer. METHODS AND MATERIALS: Three NRG trials (RTOG 9202, RTOG 9413, and RTOG 9406) that accrued from 1992 to 2000 were used. Late toxicities were measured with the Radiation Therapy Oncology Group Late Radiation Morbidity Scale. After controlling for study, age, Karnofsky Performance Status, and year of accrual, sociodemographic variables were added to the model for each outcome variable of interest in a stepwise fashion using the Fine-Gray regression models with an entry criterion of 0.05. RESULTS: A total of 2432 patients were analyzed of whom most were Caucasian (76%), had a KPS score of 90 to 100 (92%), and received whole-pelvic RT+HT (67%). Of these patients, 13 % and 16% experienced late grade ≥2 bowel and bladder toxicities, respectively, and 2% and 3% experienced late grade ≥3 bowel and bladder toxicities, respectively. Late grade ≥2 clustered bowel and bladder toxicities were seen in approximately 1% of patients and late grade ≥3 clustered toxicities were seen in 2 patients (<1%). The multivariate analysis showed that patients who received prostate-only RT+HT had a lower risk of experiencing grade ≥2 bowel toxicities than those who received whole-pelvic RT+long-term (LT) HT (hazard ratio: 0.36; 95% confidence interval, 0.18-0.73; P = .0046 and hazard ratio: 0.43; 95% confidence interval, 0.23-0.80; P = .008, respectively). Patients who received whole-pelvic RT had similar chances of having grade ≥2 bowel or bladder toxicities no matter whether they received LT or short-term HT. CONCLUSIONS: Patients with high-risk prostate cancer who receive whole-pelvic RT+LT HT are more likely to have a grade ≥2 bowel toxicity than those who receive prostate-only RT. LT bowel and bladder toxicities were infrequent. Future studies will need to confirm these findings utilizing current radiation technology and patient-reported outcomes.
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PURPOSE: Acute esophagitis is common after thoracic radiation therapy (TRT) given with chemotherapy for limited-stage small-cell lung cancer (LS SCLC). Although twice-daily TRT to 45 Gy in 30 fractions is considered standard, some clinicians are reluctant to use this schedule because of its perceived impracticality and risk of severe esophagitis. We reviewed a single-institution experience with severe (grade ≥ 3) esophagitis after TRT with chemotherapy for LS SCLC. PATIENTS AND METHODS: A total of 504 patients were identified as having received TRT (≥45 Gy) with platinum-containing chemotherapy for LS SCLC at MD Anderson Cancer Center in 1987 through 2012. Patients with complete or good partial response were offered prophylactic cranial irradiation. Esophagitis was scored retrospectively with the Common Terminology Criteria for Adverse Events, V3.0. Clinical variables were analyzed for possible association with acute grade ≥ 3 esophagitis. RESULTS: At a median follow-up time of 23.9 months (range, 1.2-240.8 months), 103 (20%) patients had experienced grade ≥ 3 esophagitis. In univariate analysis, TRT dose ≥ 60 Gy was the only factor associated with severe esophagitis (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.02-3.30; P = .043); use of twice-daily TRT was not (OR, 0.96; 95% CI, 0.61-1.52; P = .867). The significance of TRT to ≥ 60 Gy was maintained in multivariate Cox regression analysis adjusted for tumor size (OR, 1.91; 95% CI, 1.05-3.46; P = .034). CONCLUSIONS: TRT to ≥ 60 Gy predicted acute severe esophagitis, but twice-daily fractionation did not. Standard-dose 45-Gy twice-daily TRT should not be avoided for fear of severe esophagitis.
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Esofagitis/epidemiología , Neoplasias Pulmonares/radioterapia , Traumatismos por Radiación/epidemiología , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Enfermedad Aguda , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Progresión de la Enfermedad , Fraccionamiento de la Dosis de Radiación , Esofagitis/etiología , Esofagitis/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Pulmonares/mortalidad , Masculino , Traumatismos por Radiación/mortalidad , Dosificación Radioterapéutica , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
Purpose This randomized trial compared outcomes of passive scattering proton therapy (PSPT) versus intensity-modulated (photon) radiotherapy (IMRT), both with concurrent chemotherapy, for inoperable non-small-cell lung cancer (NSCLC). We hypothesized that PSPT exposes less lung tissue to radiation than IMRT and thereby reduces toxicity without compromising tumor control. The primary end points were grade ≥ 3 radiation pneumonitis (RP) and local failure (LF). Patients and Methods Eligible patients had stage IIB to IIIB NSCLC (or stage IV NSCLC with a single brain metastasis or recurrent lung or mediastinal disease after surgery) who were candidates for concurrent chemoradiation therapy. Pairs of treatment plans for IMRT and PSPT were created for each patient. Patients were eligible for random assignment only if both plans satisfied the same prespecified dose-volume constraints for at-risk organs at the same tumor dose. Results Compared with IMRT (n = 92), PSPT (n = 57) exposed less lung tissue to doses of 5 to 10 Gy(RBE), which is the absorbed Gy dose multiplied by the relative biologic effectiveness (RBE) factor for protons; exposed more lung tissue to ≥ 20 Gy(RBE), but exposed less heart tissue at all dose levels between 5 and 80 Gy(RBE). The grade ≥ 3 RP rate for all patients was 8.1% (IMRT, 6.5%; PSPT, 10.5%); corresponding LF rates were 10.7% (all), 10.9% (IMRT), and 10.5% (PSPT). The posterior probability of IMRT being better than PSPT was 0.54. Exploratory analysis showed that the RP and LF rates at 12 months for patients enrolled before versus after the trial midpoint were 21.1% (before) versus 18.2% (after) for the IMRT group (P = .047) and 31.0% (before) versus 13.1% (after) for the PSPT group (P = .027). Conclusion PSPT did not improve dose-volume indices for lung but did for heart. No benefit was noted in RP or LF after PSPT. Improvements in both end points were observed over the course of the trial.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia de Protones/métodos , Anciano , Teorema de Bayes , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioradioterapia , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Terapia de Protones/efectos adversos , Neumonitis por Radiación/etiología , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Factores de RiesgoRESUMEN
PURPOSE: To compare clinical outcomes between proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in patients with esophageal cancer (EC) treated with definitive chemoradiotherapy (CRT). METHODS AND MATERIALS: From 2007 through 2014, 343 EC patients who received definitive CRT with either PBT (n=132) or IMRT (n=211) were retrospectively analyzed. Survival, recurrence, and treatment toxicity were compared between groups. A Cox proportional hazards regression model was performed to test the association between patient/treatment variables and survival. RESULTS: Patient/treatment variables were overall well balanced, except for age and race. Compared with IMRT, PBT had significantly better overall survival (OS; P=.011), progression-free survival (PFS; P=.001), distant metastasis-free survival (DMFS; P=.031), as well as marginally better locoregional failure-free survival (LRFFS; P=.075). No significant differences in rates of treatment-related toxicities were observed between groups. On multivariate analysis, IMRT had worse OS (hazard ratio [HR] 1.454; P=.01), PFS (HR 1.562; P=.001), and LRFFS (HR 1.461; P=.041) than PBT. Subgroup analysis by clinical stage revealed considerably higher 5-year OS (34.6% vs 25.0%, P=.038) and PFS rates (33.5% vs 13.2%, P=.005) in the PBT group for patients with stage III disease. However, no significant intergroup differences in survival were identified for stage I/II patients. CONCLUSIONS: Compared with IMRT, PBT might be associated with improved OS, PFS, and LRFFS, especially in EC patients with locally advanced disease. These results need confirmation by prospective studies.
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Quimioradioterapia/métodos , Neoplasias Esofágicas/radioterapia , Terapia de Protones , Radioterapia de Intensidad Modulada , Anciano , Quimioradioterapia/efectos adversos , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia de Protones/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC. METHODS AND MATERIALS: This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications. RESULTS: The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%). CONCLUSIONS: This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.
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INTRODUCTION: Extended survival outcomes from improved treatments for patients with cancer come with an increased risk for development of a metachronous second malignancy (MSM). We evaluated the incidence of MSM after successful treatment of SCLC and compared survival between patients with SCLC in whom MSM developed and those in whom it did not. METHODS: Selection criteria were a diagnosis of limited-stage SCLC and receipt of at least 45 Gy of radiotherapy and chemotherapy at a single institution in 1985-2012. MSM was defined as a tumor of a different histologic type than the primary that appeared more than 2 years after the diagnosis of SCLC. RESULTS: Of 704 patients identified, 32 were excluded for lack of follow-up, 48 for having SCLC as MSM after treatment of another type of cancer, 37 for nonmelanoma skin cancer as MSM, and 46 for MSM within 2 years after SCLC diagnosis. Of the remaining 541 patients, 346 had recurrent SCLC, 180 had no second malignancy and no recurrence, and 15 (2.8%) had MSM (13 in a lung [eight adenocarcinomas and five squamous cell carcinomas], one sarcoma, and one acute myeloid leukemia). All 15 patients with MSM achieved complete response to the SCLC treatment. Overall survival was longer for patients with MSM than for patients with no other malignancies and no recurrence, with 10-year rates of 61.9% (95% confidence interval: 30.0%-82.6%) and 29.9% (95% confidence interval: 21.5%-38.6%), respectively (p = 0.03). CONCLUSIONS: Long-term survivors after treatment for SCLC should be made aware of the risk for MSM and the necessity of follow-up.
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Neoplasias Pulmonares/complicaciones , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Adulto , Anciano , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Análisis de SupervivenciaRESUMEN
PURPOSE: Host immunity may affect the outcome in patients with esophageal cancer. We sought to identify factors that influenced absolute lymphocyte count (ALC) nadir during chemoradiation therapy (CRT) for esophageal cancer (EC) and looked for clinically relevant associations with survival. METHODS AND MATERIALS: 504 patients with stage I-III EC (2007-2013) treated with neoadjuvant or definitive CRT with weekly ALC determinations made during treatment were analyzed. Grade of lymphopenia from ALC nadir during CRT was based on Common Terminology Criteria for Adverse Events version 4.0. Associations of ALC nadir with survival were examined using multivariate Cox proportional hazards analysis (MVA) and competing risks regression analysis. RESULTS: The median follow-up time was 36 months. The incidences of grade 1, 2, 3, and 4 ALC nadir during CRT were 2%, 12%, 59%, and 27%, respectively. The impact was lymphocyte-specific because this was not seen for monocyte or neutrophil count. On MVA, grade 4 ALC nadir (G4 nadir) was significantly associated with worse overall and disease-specific survival outcomes. Predictors of G4 nadir included distal tumor location, definitive CRT, taxane/5-fluorouracil chemotherapy, and photon-based radiation type (vs proton-based). Radiation type strongly influenced the mean body dose exposure, which was a strong predictor for G4 nadir (odds ratio 1.22 per Gray, P<.001). CONCLUSIONS: G4 nadir during CRT for EC was associated with poor outcomes, suggesting a role of host immunity in disease control. This observation provides a rationale to prospectively test chemotherapeutic and radiation treatment strategies that may have a lower impact on host immunity.
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Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/efectos adversos , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/terapia , Linfopenia/mortalidad , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/patología , Fluorouracilo/uso terapéutico , Humanos , Incidencia , Estimación de Kaplan-Meier , Recuento de Linfocitos , Linfopenia/epidemiología , Linfopenia/etiología , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/efectos de la radiación , Neutrófilos/efectos de los fármacos , Neutrófilos/efectos de la radiación , Oportunidad Relativa , Compuestos de Platino/uso terapéutico , Modelos de Riesgos Proporcionales , Terapia de Protones , Dosificación Radioterapéutica , Análisis de Regresión , Estudios Retrospectivos , Linfocitos T/efectos de los fármacos , Linfocitos T/efectos de la radiación , Taxoides/uso terapéutico , Resultado del TratamientoRESUMEN
Importance: Proton beam radiotherapy (PBT) has the potential to reduce toxic effects in the definitive management of locally advanced non-small cell lung cancer (NSCLC), but long-term prospective data are lacking. Objective: To report the final (5-year) results of a prospective study evaluating concurrent chemotherapy and high-dose PBT to treat unresectable stage III NSCLC. Design, Setting, and Participants: In this open-label, single-group assignment study, with median follow-up of 27.3 months for all patients and 79.6 months for survivors, 64 patients were enrolled and analyzed; inclusion criteria were unresectable IIIA/IIIB histologically confirmed NSCLC, Karnofsky performance status 70 to 100, and 6-month prediagnosis weight loss of no more than 10%. Staging used positron emission tomography and/or computed tomography. Induction chemotherapy was allowed. Interventions: Concurrent chemotherapy (carboplatin-paclitaxel) and passively scattered PBT (74-Gy relative biological effectiveness) in all patients. Main Outcomes and Measures: Kaplan-Meier analysis of overall survival (OS), progression-free survival (PFS), actuarial distant metastasis, and locoregional recurrence. Patterns of treatment failure were categorized as local/regional or distant. Acute and late toxic effects were prospectively assigned using Common Terminology Criteria for Adverse Events, v3.0. Results: Of 64 patients (22 [34%] female; median [range] age, 70 [37-78] years; stage IIIA, 30 [47%]; IIIB, 34 [53%]), 17 (27%) were alive at last follow-up. Median OS was 26.5 months (5-year OS, 29%; 95% CI, 18%-41%). Five-year PFS was 22% (95% CI, 12%-32%); 5-year actuarial distant metastasis and locoregional recurrence were 54% (n = 36) and 28% (n = 22), respectively. Treatment failures were largely (31 [48%] patients) distant, with low rates of crude local (10 [16%]) and regional (9 [14%]) recurrences. Rates of grade 2 and 3 acute esophagitis were 18 (28%) and 5 (8%), respectively. Acute grade 2 pneumonitis occurred in 1 (2%) patient. Late toxic effects were uncommon: 1 (2%) patient developed an esophageal stricture (grade 2) and 1 (2%) grade 4 esophagitis. Late grades 2 and 3 pneumonitis occurred in 10 (16%) and 8 (12%), respectively. Two (3%) patients developed a bronchial stricture (grade 2), and 1 (2%) a grade 4 bronchial fistula. There were no acute or late grade 5 toxic effects. Conclusions and Relevance: Concurrent chemotherapy and PBT to treat unresectable NSCLC afford promising clinical outcomes and rates of toxic effects compared with historical photon therapy data. Further optimization of proton therapy, particularly intensity-modulated proton therapy, is still needed.
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Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Paclitaxel/uso terapéutico , Terapia de Protones , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , ProtonesRESUMEN
PURPOSE: Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT). PATIENTS AND METHODS: Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization. RESULTS: RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p<0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264). CONCLUSIONS: Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.
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Quimioradioterapia , Neoplasias Esofágicas/terapia , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Terapia de Protones/métodos , Radioterapia de Intensidad Modulada/métodosRESUMEN
PURPOSE: The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). CONCLUSIONS: According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia de Protones , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Terapia de Protones/efectos adversos , Dosificación Radioterapéutica , Tasa de SupervivenciaRESUMEN
PURPOSE: Prophylactic cranial irradiation (PCI) can improve overall survival (OS) and suppress brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, PCI can be toxic. We sought to identify characteristics of patients who may not benefit from PCI. METHODS: We identified 658 patients who received chemoradiotherapy at MD Anderson in 1986-2012; 364 received PCI and 294 did not. Median follow-up time was 21.2months (range 1.2-240.8months). Cox proportional hazards regression, competing-risk regression, and Kaplan-Meier analyses were used to identify factors influencing OS and BM. RESULTS: PCI reduced risks of death [HR 0.73, 95% CI 0.61-0.88, P=0.001] and BM [HR 0.54, 95% CI 0.39-0.76, P<0.001]. Having tumors ⩾5cm increased the risk of BM [HR 1.77, 95% CI 1.22-2.55, P=0.002] but not death [HR 1.16, 95% CI 0.96-1.40, P=0.114]. Among patients ⩾70years with ⩾5-cm tumors, PCI did not improve OS [2-year rates 39.4% vs 40.9%, P=0.739]. CONCLUSIONS: PCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, older patients may be at risk from comorbidity or extracranial disease. Further work is warranted to identify patients who may not benefit from PCI.
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Neoplasias Encefálicas/secundario , Quimioradioterapia , Irradiación Craneana , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/prevención & control , Irradiación Craneana/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
CONTEXT: Intensity-modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT), and proton-beam therapy (PBT) are chemoradiotherapy modalities for treating locally advanced non-small-cell lung cancer. Although therapy is carefully planned to maximize treatment benefit while minimizing risk for adverse side effects, most patients develop radiation-induced symptom burden. OBJECTIVES: To demonstrate the MD Anderson Symptom Inventory's ability to detect fine differences in symptom development among these modalities. METHODS: This was a longitudinal observational study. Patients with unresectable primary or recurrent non-small-cell lung cancer (n = 82) underwent 3DCRT, IMRT, or PBT. Patients rated MD Anderson Symptom Inventory symptoms weekly for up to 12 weeks. We used mixed-effect modeling to estimate development of symptoms and functional interference. RESULTS: The PBT group received a significantly higher radiation target dose than did the IMRT and 3DCRT groups (P < 0.001). Fatigue was the most severe symptom over time for all groups. Controlling for patient and clinical factors (age, sex, race, cancer stage, performance status, body mass index, previous cancer therapy, total radiation dose), we found that pain, as a major esophagitis-related symptom, increased more during therapy (P = 0.019) and decreased more after (P = 0.013) therapy in the 3DCRT and IMRT groups than in the PBT group. Compared with the PBT group, the 3DCRT and IMRT groups reported greater decrease in systemic symptoms (fatigue, drowsiness, lack of appetite, disturbed sleep) after therapy (P = 0.016). CONCLUSION: Patients receiving PBT reported significantly less severe symptoms than did patients receiving IMRT or 3DCRT. These results should be confirmed in a randomized study with comparable tumor burden among therapies.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Costo de Enfermedad , Neoplasias Pulmonares/terapia , Terapia de Protones , Radioterapia Conformacional , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Quimioradioterapia/efectos adversos , Quimioradioterapia/psicología , Fatiga/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Dolor/fisiopatología , Estudios Prospectivos , Terapia de Protones/efectos adversos , Terapia de Protones/psicología , Dosis de Radiación , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/psicología , AutoinformeAsunto(s)
Ensayos Clínicos como Asunto , Cobertura del Seguro , Neoplasias/radioterapia , Terapia de Protones , Factores de Edad , Instituciones Oncológicas/economía , Ensayos Clínicos como Asunto/economía , Habilitación Profesional , Apoyo Financiero , Humanos , Reembolso de Seguro de Salud , Estudios Multicéntricos como Asunto , Neoplasias Inducidas por Radiación , Fotones/efectos adversos , Fotones/uso terapéutico , Terapia de Protones/efectos adversos , Terapia de Protones/economía , Terapia de Protones/instrumentación , Traumatismos por Radiación/economía , Traumatismos por Radiación/prevención & control , Traumatismos por Radiación/terapia , Sistemas de Información Radiológica , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study. METHODS: All patients received passive-scatter proton therapy, planned with 4D-CT-based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS). RESULTS: The 134 patients (21 stage II, 113 stage III; median age 69 years) had a median gross tumor volume (GTV) of 70 cm(3) (range, 5-753 cm(3)); 77 patients (57%) received 74 Gy(RBE), and 57 (42%) received 60-72 Gy(RBE) (range, 60-74.1 Gy(RBE)). At a median follow-up time of 4.7 years, median OS times were 40.4 months (stage II) and 30.4 months (stage III). Five-year DFS rates were 17.3% (stage II) and 18.0% (stage III). OS, DFS, and local and distant control rates at 5 years did not differ by disease stage. Age and GTV were related to OS and DFS. Toxicity was tolerable, with 1 grade 4 esophagitis and 16 grade 3 events (2 pneumonitis, 6 esophagitis, 8 dermatitis). CONCLUSION: This report of outcomes after proton therapy for 134 patients indicated that this regimen produced excellent OS with tolerable toxicity.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/terapia , Terapia de Protones , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Esofagitis/etiología , Esofagitis/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Terapia de Protones/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: Acute effects of incidental cardiac irradiation in patients treated for thoracic cancer are not well characterized. We evaluated longitudinal changes in cardiac biomarkers for patients undergoing conformal radiation therapy (RT) with thoracic malignancies with high-dose cardiac exposure. METHODS: Twenty-five patients enrolled in a prospective trial (February 2009-December 2012) received more than or equal to 45 Gy to the thorax, with pretreatment estimates of more than or equal to 20 Gy to the heart. Chemotherapy was allowed except for doxorubicin or fluorouracil. Electrocardiographic (ECG), troponin-I (TnI), and brain natriuretic peptide (BNP) measurements were obtained before RT, within 24 hours of the first fraction, at the end of RT, and at first follow-up (1-2 months). These biomarkers were quantified at specific times and changes from baseline were evaluated with paired t tests. RESULTS: The median heart dose was 25.9 Gy (range 10.1-35.1 Gy). After the first RT fraction, no changes were noted in ECG or median TnI or BNP levels; at the end of RT, two patients had elevated TnI and BNP, but neither difference was statistically significant. At first follow-up, TnI had returned to normal but the median BNP remained elevated (p = 0.042). BNP did not increase over time in the 18 patients who received only RT. Twelve patients experienced acute ECG changes during RT, which resolved in seven patients by the next measurement. No patients experienced clinically significant RT-related events. CONCLUSION: Increases in BNP and ECG changes were observed during high doses of radiation to the heart. The findings of this pilot study warrant further investigation and validation.
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Electrocardiografía/métodos , Cardiopatías/fisiopatología , Corazón/efectos de la radiación , Traumatismos por Radiación/fisiopatología , Neoplasias Torácicas/radioterapia , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Cardiopatías/etiología , Cardiopatías/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/metabolismo , Estudios Prospectivos , Traumatismos por Radiación/etiología , Traumatismos por Radiación/metabolismo , Radioterapia Conformacional/efectos adversos , Radioterapia Conformacional/métodos , Neoplasias Torácicas/metabolismo , Troponina I/metabolismoRESUMEN
PURPOSE: The primary aim of this study was to evaluate the impact of the interplay effects of intensity modulated proton therapy (IMPT) plans for lung cancer in the clinical setting. The secondary aim was to explore the technique of isolayered rescanning to mitigate these interplay effects. METHODS AND MATERIALS: A single-fraction 4-dimensional (4D) dynamic dose without considering rescanning (1FX dynamic dose) was used as a metric to determine the magnitude of dosimetric degradation caused by 4D interplay effects. The 1FX dynamic dose was calculated by simulating the machine delivery processes of proton spot scanning on a moving patient, described by 4D computed tomography during IMPT delivery. The dose contributed from an individual spot was fully calculated on the respiratory phase that corresponded to the life span of that spot, and the final dose was accumulated to a reference computed tomography phase by use of deformable image registration. The 1FX dynamic dose was compared with the 4D composite dose. Seven patients with various tumor volumes and motions were selected for study. RESULTS: The clinical target volume (CTV) prescription coverage for the 7 patients was 95.04%, 95.38%, 95.39%, 95.24%, 95.65%, 95.90%, and 95.53% when calculated with the 4D composite dose and 89.30%, 94.70%, 85.47%, 94.09%, 79.69%, 91.20%, and 94.19% when calculated with the 1FX dynamic dose. For these 7 patients, the CTV coverage calculated by use of a single-fraction dynamic dose was 95.52%, 95.32%, 96.36%, 95.28%, 94.32%, 95.53%, and 95.78%, with a maximum monitor unit limit value of 0.005. In other words, by increasing the number of delivered spots in each fraction, the degradation of CTV coverage improved up to 14.6%. CONCLUSIONS: A single-fraction 4D dynamic dose without rescanning was validated as a surrogate to evaluate the interplay effects of IMPT for lung cancer in the clinical setting. The interplay effects potentially can be mitigated by increasing the amount of isolayered rescanning in each fraction delivery.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Terapia de Protones , Planificación de la Radioterapia Asistida por Computador/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Fraccionamiento de la Dosis de Radiación , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Estadificación de Neoplasias , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Mecánica RespiratoriaRESUMEN
PURPOSE: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. METHODS AND MATERIALS: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). RESULTS: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. CONCLUSIONS: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of locoregional recurrence and distant metastasis are high, and patients should be selected carefully to maximize the benefit of additional aggressive local therapy while minimizing the risk of adverse side effects.