Background: Reirradiation (reRT) for locoregional recurrences can provide durable control and improved symptoms and progression-free survival for select NSCLC patients. Thoracic reRT, however, is particularly challenging due to its considerable risk and the current lack of standardized approaches, guidelines and dose constraints. To date, no systematic review on the safety and efficacy of reRT for NSCLC exists, and no dedicated guidelines are available. Objectives: This ARS-ACR Appropriate Use Criteria Systematic Review and Guidelines on Reirradiation for NSCLC provides direct guidance on the safety and efficacy of reRT and recommends consensus dose constraints for thoracic reRT to minimize risks of high grade toxicities. Methods: A PRISMA systematic review assessed all studies published through 3/2019 evaluating toxicities, local control and/or overall survival for NSCLC thoracic reRT. Of 236 articles, 49 remained after exclusions (3 prospective) and formed the basis for these recommendations on: 1) the role of concurrent chemotherapy with reRT, 2) factors associated with toxicity from reRT and 3) what reRT modalities, dose-fractionation schemas and dose rates should be used. Composite dose constraints were also recommended. Results: The available data suggest potential benefit in clinical outcomes with concurrent chemoradiation for reRT, but the decision should be based on patient performance status, tolerance to prior systemic therapy and other individual patient/tumor characteristics. There are no data to guide the use of concurrent targeted therapy or immunotherapy with reRT, and this is not recommended outside of a clinical trial. Acute esophagitis and pneumonitis and late pulmonary, cardiac/great vessel, esophageal, brachial plexus and spinal toxicities are dose limiting for reRT. Limited data exist regarding the use of hyperfractionation and low-or high-dose rate reRT for NSCLC. For conventionally fractionated reRT, intensity-modulated radiation therapy (IMRT) is recommended over 3D conformal radiation therapy (3DCRT) to increase dose conformality. Particle therapy may further reduce toxicities and/or enable safer reRT dose escalation compared with 3DCRT and IMRT. Stereotactic body radiation therapy (SBRT) can provide increased conformality and dose escalation and is optimal for primary-alone failures, but caution is needed for central reRT with SBRT. Recommended reRT composite dose constraints in 2 Gy equivalent dose are: esophagus V60 <40% and DMax <100-110 Gy, lung V20 <40%, heart V40 <50%, aorta/great vessels DMax <120 Gy, trachea and proximal bronchial tree DMax <110 Gy, spinal cord DMax <57 Gy, and brachial plexus DMax <85 Gy. Conclusions: For the first time, consensus dose constraints for thoracic reRT are recommended to minimize the risks of high-grade and potentially fatal toxicities from repeat radiotherapy. Additional prospective data are needed, and toxicities should be correlated with reRT course and composite dose constraints.
To report on the feasibility and performance of conventionally fractionated multileaf collimator (MLC)-based robotic stereotactic body re-irradiation of the head and neck region using MLC-based Cyberknife (CK) technology. Methods: Patients treated for recurrent or second primary head and neck cancer (HNC) with curative proton therapy to a target volume > 30 cm 3 between 2011 and 2015 were included. MLC-based CK plans were generated using the CK M6 InCise2 MLC system. Dose statistics from MLC-based CK plans were compared to proton beam therapy (PBT) plans according to the following metrics: target coverage, target homogeneity index, gradient index, Paddick conformity index (CI), prescription isodose volume (PIV), treatment time (tTime) for one fraction as well as doses to organs at risk (OAR). Wilcoxon signed-rank test was used to compare dose metrics. Results: Eight patients were included; the tumor sites included: salivary glands, pharynx (oropharynx, hypopharynx and retropharynx) and sinonasal cavities. Five of 8 patients were treated with multifield optimisation intensity modulated proton therapy, 3 were treated with passive scattering proton therapy. Median dose was 67 Gy (range 60-70) in 32 fractions (range 30-35). The median high-dose planning target volume (PTV) was 45.4 cm 3 (range 2.4-130.2 cm 3) and the median elective PTV was 91.9 cm 3 (range 61.2-269.7 cm 3). Overall, the mean target coverage (mean 98.3% vs. 96.2% for CK vs. PBT, respectively), maximum dose to PTV (mean 111% vs. 111%, p = 0.2) and mean dose to PTV (mean 104% vs. 104%) were similar across modalities. Highly conformal plans were achieved with both modalities, but mean CI was better with PBT (0.5 vs. 0.6 for CK vs. PBT, p = 0.04). Homogeneity and gradient indexes were similar between the 2 modalities; mean tTime with PBT and CK was 17 vs. 18 min, respectively (p = 0.7). Case-based study revealed that CK and PBT plans allowed for excellent sparing of OAR, with some clinical scenarios associated with better performance of CK while others with better performance of PBT. Conclusion: Our study has demonstrated the dosimetric performance of large volume head and neck reirradiation using MLC-based CK in various clinical scenarios. While conformity was generally better achieved with PBT, MLC-based CK allowed for high dose gradient leading to rapid dose drop-off and sparing of OAR. Conventionally fractionated MLC-based CK could be a competitive alternative in large volume head and neck re-irradiation that deserves further investigation in the clinical setting.
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