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Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors.

ABSTRACT: Stereotactic body radiotherapy (SBRT) to central lung tumors can cause esophageal toxicity, but little is known about the incidence or risk factors. We reviewed central lung SBRT patients to identify dosimetric factors predictive of esophageal toxicity.We assessed esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with ?/?=10 Gy (BED??), dose-volume histogram variables for the esophagus (Dv and Vd) were assessed for correlation with grade ?2 acute toxicity.Incidence of grade ?2 acute toxicity was 12% (n=15). Highly significant logistic models were generated for D?cc and Dmax (p<0.001). To keep the complication rate <20%, the model requires that D?cc?26.3 BED??. At 2 years, the probability of complication with BED??D?cc>14.4 Gy was 24%, compared to 1.6% if ?14.4 Gy.This novel analysis provides guidelines to predict acute esophageal toxicity in lung SBRT. Dose to the hottest 5cc and Dmax of the esophagus were the best predictors of toxicity. Converting the BED?? limits to physical doses, D?cc to the esophagus should be kept less than 16.8, 18.1 and 19.0 Gy for 3, 4, and 5 fractions, respectively, to keep the acute toxicity rate <20%.

SUBMITTER: Wu AJ

PROVIDER: S-EPMC4254177 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors.

Wu Abraham J AJ Williams Eric E Modh Ankit A Foster Amanda A Yorke Ellen E Rimner Andreas A Jackson Andrew A

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20140723 2

<h4>Background and purpose</h4>Stereotactic body radiotherapy (SBRT) to central lung tumors can cause esophageal toxicity, but little is known about the incidence or risk factors. We reviewed central lung SBRT patients to identify dosimetric factors predictive of esophageal toxicity.<h4>Materials and methods</h4>We assessed esophageal toxicity in 125 SBRT patients. Using biological equivalent doses with α/β=10 Gy (BED₁₀), dose-volume histogram variables for the esophagus (Dv and Vd) were assesse ...[more]

PMID: 25064471

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Project description:PurposeStereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters.Methods and materialsWe identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.ResultsOne hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT ("no-fly-zone" [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.ConclusionsUsing moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.

Project description:Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ?2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ?2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

Project description:BackgroundLung stereotactic ablative radiotherapy (SABR) is associated with low morbidity, however there is an increased risk of treatment-related toxicity in tumors directly abutting or invading the proximal bronchial tree, termed 'ultra-central' tumors. As there is no consensus regarding the optimal radiotherapy treatment regimen for these tumors, we performed a modeling study to evaluate the trade-offs between predicted toxicity and local control for commonly used high-precision dose-fractionation regimens.MethodsTen patients with ultra-central lung tumors were identified from our institutional database. New plans were generated for 3 different hypofractionated schemes: 50 Gy in 5 fractions, 60 Gy in 8 fractions and 60 Gy in 15 fractions. For each regimen, one plan was created that prioritized planning target volume (PTV) coverage, potentially at the expense of organ at risk (OAR) tolerance, and a second that compromised PTV coverage to respect OAR dose constraints. Published radiobiological models were employed to evaluate competing treatment plans based on estimates for local control and the likelihood for toxicity to OAR.ResultsThe risk of esophageal or pulmonary toxicity was low (< 5%) in all scenarios. When PTV coverage was prioritized, tumor control probabilities were 92.9% for 50 Gy in 5 fractions, 92.4% for 60 Gy in 8 fractions, and 52.0% for 60 Gy in 15 fractions; however the estimated risk of grade ≥ 4 toxicity to the proximal bronchial tree was 68%, 44% and 2% respectively. When dose to OAR was prioritized, the risk of major pulmonary toxicity was reduced to < 1% in all schemes, but this compromise reduced tumor control probability to 60.3% for 50 Gy in 5 fractions, 65.7% for 60 Gy in 8 fractions and 47.8% for 60 Gy in 15 fractions.ConclusionsThe tradeoff between local control and central airway toxicity are considerable in the use of 3 commonly used hypofractionated radiotherapy regimens for ultra-central lung cancer. The results of this planning study predict that the best balance may be achieved with 60 Gy in 8 fractions compromising PTV coverage as required to maintain acceptable doses to OAR. A prospective phase I trial (SUNSET) is planned to further evaluate this challenging clinical scenario.

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Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors.

Publications

Dosimetric predictors of esophageal toxicity after stereotactic body radiotherapy for central lung tumors.

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