EP-1404: Non-linear radiomic signatures characterizing overall survival from non-small cell lung cancer (original) (raw)
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Fuel and Energy Abstracts, 2000
Purpose: Patients treated with chemoradiotherapy for locally advanced non-small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control and survival in the setting of chemoradiotherapy. Ó 2012 Elsevier Inc.
Medical Dosimetry, 2017
The patients with non-small cell lung cancer (NSCLC) treated with definitive conformal radiotherapy (RT) were evaluated in terms of side effects and survival. Normal tissue complication probability (NTCP) was calculated for 68 patients treated between 2009 and 2012. Clinical and dosimetric factors were analyzed. The median dose of 63 Gy (range: 54 to 70 Gy) was given with conformal RT with blocks (n = 37), 3-dimensional conformal RT (3DCRT) (n = 11), or intensity-modulated RT (IMRT) (n = 20). Acute grade 1 to 2 radiation pneumonitis (RP) was seen in 13% of the patients. No significant relationship was found between RP and treatment and dosimetric factors (p > 0.05). There was a positive correlation between median "mean lung dose" (MLD) (17 Gy), lung V30 (20.5%), and NTCP (14%) (p < 0.001). Median and 2-year overall survival (OS) and progression-free survival (PFS) were 27 and 18 months and 51% and 42%, respectively. In univariate analysis, significant dose range for survival was found between 59.4 and 63 Gy (p < 0.01). In multivariate analysis, response (p = 0.001), fraction dose of 1.8 Gy (p = 0.002), MLD <18 Gy (p = 0.04) for OS and response (p < 0.001), total dose > 59.4 Gy (p = 0.01), and tumor biologically effective dose (BED)3(Gy) ≤ 100.8 (p = 0.01) for PFS were found to be favorable factors. In our study, we found a linear correlation between NTCP and MLD for RP risk estimation in patients with NSCLC. Therapeutic dose range where MLD can be kept under 20 Gy with significant survival benefit was found between 59.4 and 63 Gy. Increased therapeutic efficacy will be possible using risk-adaptive RT techniques.
Clinical Lung Cancer, 2014
We retrospectively identified imaging-based biomarkers in 117 patients with stage I nonesmall-cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR). Tumor size, contact with the mediastinal pleura, and maximum standard uptake value (SUVmax) significantly correlated with distant metastasis and were incorporated into a prognostic index that could be used to identify patients most likely to benefit from adjuvant systemic therapy following SABR. Introduction/Background: The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC. Patients and Methods: Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax. Results: Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases. Conclusion: In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR.
Frontiers in Oncology, 2018
Radical radiotherapy (RT) is a potentially curative treatment in non-small cell lung cancer (NSCLC) and is delivered in conventional 2-Gy fractions, hypofractionated and ablative stereotactic courses. No reliable, predictive biomarkers for the clinical events of local control, appearance of distant metastases and development of toxicity have been introduced in routine clinical practice. Such a test would enable the Radiotherapist to tailor the clinical management of individual patients, considering their pre-treatment characteristics, in order reduce the risk of recurrence or toxicity e.g., dose modification, accelerated fractionation, hypofractionation, or concurrent systemic therapy. The aim of this review was to map the published literature relating to investigations of the potential predictive value of patient or treatment characteristics in radical RT for NSCLC. These investigations should remain a research focus for disease control given the upward trends in lung cancer incidence, and for the avoidance of toxicity, given the survivorship afforded to the cohort of patients that do well with radical RT, or with the increasing range of systemic agents following metastatic relapse. The conclusion of the presented analysis is that there are no published, effective and validated predictive tools for estimation of risk of local/distant recurrence or toxicity after radical RT for NSCLC. The authors have identified an important space for future research in the field of lung cancer radiotherapy.
Influence of tumor volume on survival in patients irradiated for non--small-cell lung cancer* 1
International Journal of …, 2002
Methods and Materials: Between 1991 and 1998, 150 evaluable patients with Stage I-IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall-Wallis analysis of variance and Kaplan-Meier actuarial method. To account for the potentially confounding effects of therapeutic and patientspecific covariates on survival, the Cox proportional hazard regression model was used.
Influence of tumor volume on survival in patients irradiated for non—small-cell lung cancer
International Journal of Radiation Oncology*Biology*Physics, 2002
Methods and Materials: Between 1991 and 1998, 150 evaluable patients with Stage I-IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall-Wallis analysis of variance and Kaplan-Meier actuarial method. To account for the potentially confounding effects of therapeutic and patientspecific covariates on survival, the Cox proportional hazard regression model was used.
International Journal of Radiation Oncology*Biology*Physics, 2009
To investigate the possible influences of various factors on tumor response to radiation, regression speeds and long-term local control rates of primary adenocarcinoma and squamous cell carcinoma of the lung after stereotactic body radiotherapy were evaluated. Ninety-one patients (65 men and 26 women) with a median age of 76 years were serially examined using computed tomography at 2, 4 and 6 months after treatment. Tumor histology was adenocarcinoma in 62 patients and squamous cell carcinoma in 29 patients. The prescribed dose was 48 Gy in four fractions given twice a week for T1 tumors (≤3 cm) and 52 Gy in four fractions given twice a week for T2 tumors (3-5 cm). Tumor shrinkage speed and 3-year local control rates were similar between T1 and T2 tumors and between patients with normal pulmonary function and those with impaired function. Squamous cell carcinomas shrank faster than adenocarcinomas at 2 and 4 months after radiation, but mean relative tumor size at 6 months and local control rates at 3 years did not differ significantly between the two histologies. Tumors in patients with a higher hemoglobin level tended to shrink faster but the control rates were not different. It is concluded that, although squamous cell carcinoma shrinks faster than adenocarcinoma, the two types of lung cancer are of similar radiosensitivity in terms of longterm control rates. Radiosensitivity should not be evaluated by early tumor response. (Cancer Sci 2013; 104: 130-134) T he radiosensitivity of tumors varies with various tumorand patient-related factors. These include histology, grade of differentiation and size of tumors, and hemoglobin levels in patients. It is well known that small-cell carcinoma of the lung responds more quickly to radiation than other histological subtypes of lung cancer. In uterine cervical cancer treated with radiation, squamous cell carcinoma (SCC) is generally associated with a better prognosis than adenocarcinoma (AD); (1,2) such observations led many oncologists to assume that SCC is more radiosensitive than AD. In addition, smaller tumors are generally more radiosensitive than larger ones. (5,6) Furthermore, extensive clinical data show that patients with a high hemoglobin level have a better prognosis than those with a low level following definitive radiotherapy of various cancers, indicating that tumors in patients with a high hemoglobin level might be more radiosensitive than tumors in those with a low hemoglobin level. However, these observations mostly come from retrospective analyses of clinical data and have not been properly evaluated in a prospective study.
International Journal of Radiation Oncology*Biology*Physics, 2015
The aim of the study was to evaluate the prognostic significance of the modified Glasgow Prognostic Score in patients with non-small cell lung cancer who received stereotactic body radiaton therapy to find a predictor with higher sensitivity and specificity using blood examination data commonly available in clinical settings. Purpose: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). Methods and Materials: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. Results: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (PZ.019) and distant metastasis (PZ.013). Conclusions: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.
Lung Cancer, 2012
Stereotactic ablative radiotherapy (SABR)/Stereotactic body radiation therapy (SBRT) Positron emission tomography (PET) Standardized uptake value (SUV) Metabolic tumor volume (MTV) Non-small cell lung cancer (NSCLC) a b s t r a c t Background and Purpose: To test whether 18 F-fluorodeoxyglucose (FDG) positron emission tomographycomputed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I nonsmall cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR). Material and Methods: Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUV max ) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancerspecific survival (CSS). We performed Kaplan-Meier, competing risk, and Cox proportional hazards survival analyses. Results: Patients received 25-60 Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUV max (p = 0.014), MTV 7 (p = 0.0077), and MTV 10 (p = 0.0039) correlated significantly with OS. In the low-MTV 7 vs. high-MTV 7 sub-groups, 1-year estimated OS was 100 vs. 78% (p = 0.0077) and CSS was 100 vs. 88% (p = 0.082). Conclusions: In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid riskstratification and treatment individualization if validated prospectively.