Cardiovascular Substructure Dose and Cardiac Events following Proton- and Photon-Based Chemoradiotherapy for Non-Small Cell Lung Cancer.

Purpose: Radiation therapy (RT) plays a critical role in treating locally advanced non-small cell lung cancer but has been associated with deleterious cardiac effects. We hypothesized that RT dose to certain cardiovascular substructures may be higher among those who experience post-chemoradiation (CRT) cardiac events, and that dose to specific substructures-the great vessels, atria, ventricles, and left anterior descending coronary artery-may be lower with proton- versus photon-based RT. Methods and Materials: In this retrospective review, we selected 26 patients who experienced cardiac events after CRT for locally advanced non-small cell lung cancer and matched them to 26 patients who did not experience cardiac events after CRT. Matching was done based on RT technique (protons vs photons), age, sex, and cardiovascular comorbidity. For each patient, the whole heart and 10 cardiovascular substructures on the RT planning computerized tomography scan were manually contoured. Dosimetric comparisons were made between those who did and did not experience cardiac events and between the proton and photon groups. Results: There was no significant difference in heart or any cardiovascular substructure dose between those patients who experienced post-treatment cardiac events and those who did not (P > .05 for all). The mean heart dose in the patients receiving proton therapy was significantly lower than the mean heart dose in the patients receiving photon therapy (P = .032). The left ventricle, right ventricle, and the left anterior descending artery also had significantly lower doses (by multiple measures) when treated with protons (P = .0004, P < .0001, and P = .0002, respectively). Conclusions: Proton therapy may have a significant effect on decreasing dose to individual cardiovascular substructures compared with photon therapy. There was no significant difference in heart dose or dose to any cardiovascular substructure between patients who did and did not experience post-treatment cardiac events. Further research should be done to assess the association between cardiovascular substructure dose and post-treatment cardiac events.

Death without progression as an endpoint to describe cardiac radiation effects in locally advanced non-small cell lung cancer.

Background and purpose: Prior studies have examined associations of cardiovascular substructure dose with overall survival (OS) or cardiac events after chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC). Herein, we investigate an alternative endpoint, death without cancer progression (DWP), which is potentially more specific than OS and more sensitive than cardiac events for understanding CRT toxicity. Materials and methods: We retrospectively reviewed records of 187 patients with locally advanced or oligometastatic NSCLC treated with definitive CRT from 2008 to 2016 at a single institution. Dosimetric parameters to the heart, lung, and ten cardiovascular substructures were extracted. Charlson Comorbidity Index (CCI), excluding NSCLC diagnosis, was used to stratify patients into CCI low (0-2; n = 66), CCI intermediate (3-4; n = 78), and CCI high (≥5; n = 43) groups. Primary endpoint was DWP, modeled with competing risk regression. Secondary endpoints included OS. An external cohort consisted of 140 patients from another institution. Results: Median follow-up was 7.3 years for survivors. Death occurred in 143 patients (76.5 %), including death after progression in 118 (63.1 %) and DWP in 25 (13.4 %). On multivariable analysis, increasing CCI stratum and mean heart dose were associated with DWP. For mean heart dose ≥ 10 Gy vs < 10 Gy, DWP was higher (5-year rate, 16.9 % vs 6.7 %, p = 0.04) and OS worse (median, 22.9 vs 34.1 months, p < 0.001). Ventricle (left, right, and bilateral) and pericardial but not atrial substructure dose were associated with DWP, whereas all three were inversely associated with OS. Cutpoint analysis identified right ventricle mean dose ≥ 5.5 Gy as a predictor of DWP. In the external cohort, we confirmed an association of ventricle, but not atrial, dose with DWP. Conclusion: Cardiovascular substructure dose showed distinct associations with DWP. Future cardiotoxicity studies in NSCLC could consider DWP as an endpoint.

Intracranial Grade II Meningioma Oligometastatic to the Cervical Spine.

For intracranial meningiomas that metastasize extracranially, an oligometastatic state exists that is intermediate between incurable, widely metastatic disease and non-metastatic curable disease. Similar to oligometastatic cancer, aggressive local treatment of meningioma oligometastases is warranted, as it may be curable. We present a patient with multiply recurrent intracranial meningiomas over 19 years, with a transformation from grade I to grade II histology, with oligometastatic disease to the C5 vertebral body. Three years following definitive spinal stereotactic radiosurgery, she remains without evidence of other metastatic diseases. Our case highlights the oncologic concept that metastatic meningioma need not be widely disseminated and provides the clinical rationale for aggressive local treatment of an oligometastatic meningioma.