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Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

ABSTRACT: Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the current standard of care using parallel-opposed pair beams (POP).In this study, 15 patients with lung cancer treated to a dose of 30Gy in 10 fractions between August 2015 and January 2016 were identified. Radiation treatment plans were optimized using ES-IMRT by limiting the max esophagus point dose to 24Gy. Using published Lyman-Kutcher-Burman normal tissue complication probabilities (LKB-NTCP) models, both plans were evaluated for the likelihood of esophagitis (? grade 2) and pneumonitis (? grade 2).Using ES-IMRT, the median esophageal and lung mean doses reduced from 16 and 8Gy to 7 and 7Gy, respectively. Using the LKB models, the theoretical probability of symptomatic esophagitis and pneumonitis reduced from 13 to 2%, and from 5 to 3%, respectively. The median normalize total dose (NTD mean) accounting for fraction size for the GTV and PTV of the clinically approved POP plans compared to the ES-IMRT plans were similar.Advanced radiotherapy techniques such as ES-IMRT may have clinical utility in reducing treatment-related toxicity in advanced lung cancer patients. Our data suggests that the rate of esophagitis can be reduced without compromising local control.

SUBMITTER: Granton PV

PROVIDER: S-EPMC5267414 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

Granton Patrick V PV Palma David A DA Louie Alexander V AV

Radiation oncology (London, England) 20170126 1

<h4>Background</h4>Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy<sub>10</sub> or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the curren ...[more]

PMID: 28122566

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Project description:ImportancePalliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear.ObjectiveTo examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT.Design, setting, and participantsPalliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between June 24, 2016, and March 6, 2019. Data analysis was conducted from January 23, 2020, to October 22, 2021. Patients had up to 1 year of follow-up. Ninety patients at 6 tertiary academic cancer centers who had stage III/IV NSCLC and were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) were included.InterventionsPatients were randomized (1:1) to standard RT (control arm) or ES-IMRT. Target coverage was compromised to ensure the maximum esophagus dose was no more than 80% of the RT prescription dose.Main outcomes and measuresThe primary outcome was esophageal quality of life (QOL) 2 weeks post-RT, measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy: Esophagus questionnaire. Higher esophageal cancer subscale scores correspond with improved QOL, with a 2- to 3-point change considered clinically meaningful. Secondary outcomes included overall survival, toxic events, and other QOL metrics. Intention-to-treat analysis was used.ResultsBetween June 24, 2016, and March 6, 2019, 90 patients were randomized to standard RT or ES-IMRT (median age at randomization, 72.0 years [IQR, 65.6-80.3]; 50 [56%] were female). Thirty-six patients (40%) received 20 Gy and 54 (60%) received 30 Gy. For the primary end point, the mean (SD) 2-week ECS score was 50.5 (10.2) in the control arm (95% CI, 47.2-53.8) and 54.3 (7.6) in the ES-IMRT arm (95% CI, 51.9-56.7) (P = .06). Symptomatic RT-associated esophagitis occurred in 24% (n = 11) of patients in the control arm vs 2% (n = 1) in the ES-IMRT arm (P = .002). In a post hoc subgroup analysis based on the stratification factor, reduction in esophagitis was most evident in patients receiving 30 Gy (30% [n = 8] vs 0%; P = .004). Overall survival was similar with standard RT (median, 8.6; 95% CI, 5.7-15.6 months) and ES-IMRT (median, 8.7; 95% CI, 5.1-10.2 months) (P = .62).Conclusions and relevanceIn this phase 3 randomized clinical trial, ES-IMRT did not significantly improve esophageal QOL but significantly reduced the incidence of symptomatic esophagitis. Because post hoc analysis found that reduced esophagitis was most evident in patients receiving 30 Gy of RT, these findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy).Trial registrationClinicalTrials.gov Identifier: NCT02752126.

Project description:PurposeIntensity-modulated radiation therapy (IMRT) has allowed optimization of three-dimensional spatial radiation dose distributions permitting target coverage while reducing normal tissue toxicity. However, radiation-induced normal tissue toxicity is a major contributor to patients' quality of life and often a dose-limiting factor in the definitive treatment of cancer with radiation therapy. We propose the next logical step in the evolution of IMRT using canonical radiobiological principles, optimizing the temporal dimension through which radiation therapy is delivered to further reduce radiation-induced toxicity by increased time for normal tissue recovery. We term this novel treatment planning strategy "temporally feathered radiation therapy" (TFRT).MethodsTemporally feathered radiotherapy plans were generated as a composite of five simulated treatment plans each with altered constraints on particular hypothetical organs at risk (OARs) to be delivered sequentially. For each of these TFRT plans, OARs chosen for feathering receive higher doses while the remaining OARs receive lower doses than the standard fractional dose delivered in a conventional fractionated IMRT plan. Each TFRT plan is delivered a specific weekday, which in effect leads to a higher dose once weekly followed by four lower fractional doses to each temporally feathered OAR. We compared normal tissue toxicity between TFRT and conventional fractionated IMRT plans by using a dynamical mathematical model to describe radiation-induced tissue damage and repair over time.ResultsModel-based simulations of TFRT demonstrated potential for reduced normal tissue toxicity compared to conventionally planned IMRT. The sequencing of high and low fractional doses delivered to OARs by TFRT plans suggested increased normal tissue recovery, and hence less overall radiation-induced toxicity, despite higher total doses delivered to OARs compared to conventional fractionated IMRT plans. The magnitude of toxicity reduction by TFRT planning was found to depend on the corresponding standard fractional dose of IMRT and organ-specific recovery rate of sublethal radiation-induced damage.ConclusionsTFRT is a novel technique for treatment planning and optimization of therapeutic radiotherapy that considers the nonlinear aspects of normal tissue repair to optimize toxicity profiles. Model-based simulations of TFRT to carefully conceptualized clinical cases have demonstrated potential for radiation-induced toxicity reduction in a previously described dynamical model of normal tissue complication probability (NTCP).

Project description:Objective.Reducing plan complexity in intensity modulated radiation therapy (IMRT) to ensure dosimetric accuracy and delivery efficiency of the radiation treatment plans. We propose a novel approach by representing the beamlet intensities using an incomplete wavelet basis that explicitly excludes fluctuating intensity maps from the decision space (explicit hard constraint). This technique provides a built-in wavelet-induced smoothness that improves both dosimetric plan quality and delivery efficiency.Approach.The beamlet intensity maps need to be especially smooth in the leaf travel direction (referred to as theX-direction). We treat the intensity map of each beam as a 2D image and represent it using the wavelets corresponding to low-frequency changes in theX-direction (i.e. approximation and horizontal). The absence of wavelets corresponding to high-frequency changes (i.e. vertical and diagonal) induces built-in smoothness. We still utilize a regularization term in the objective function to promote smoothness in theY-direction (perpendicular to theX-direction) and further possible smoothness in theX-direction. This technique has been tested on three patient cases of different disease sites (paraspinal, lung, prostate) and all final evaluations and comparisons have been performed on an FDA-approved commercial treatment planning system (Varian EclipseTM).Main results.Wavelet-induced smoothness reduced monitor units by about 10%, 45%, and 14% for paraspinal, lung, and prostate cases, respectively. It also improved organ at risk sparing, especially on the complex paraspinal case where it resulted in about 7%, 13%, and 14% less mean dose to esophagus, lung, and cord, respectively. Moreover, built-in wavelet-induced smoothness desensitizes the results to changing the weight associated to the regularization term, and thereby mitigates the weight fine-tuning difficulty.Significance.Fluence smoothness is often achieved by smoothing the beamlet intensity maps using a proper regularization term in the objective function aiming at disincentivizing fluctuation in the beamlet intensities (implicit soft constraint). This work reports a novel application of wavelets in imposing an explicit smoothness hard constraint in the search space using an incomplete wavelet basis. This idea has been successfully applied to exclude complex and clinically irrelevant radiation plans from the search space. The code and pertained models along with a sample dataset are released on our LowDimRT GitHub (https://github.com/PortPy-Project/LowDimRT).

Dataset Information

Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

Publications

Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

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