Synergistic combination of a topologically invariant imaging signature and a biomarker for the accurate prediction of symptomatic radiation pneumonitis before stereotactic ablative radiotherapy for lung cancer: A retrospective analysis.

OBJECTIVES: We aimed to explore the synergistic combination of a topologically invariant Betti number (BN)-based signature and a biomarker for the accurate prediction of symptomatic (grade ≥2) radiation-induced pneumonitis (RP+) before stereotactic ablative radiotherapy (SABR) for lung cancer. METHODS: A total of 272 SABR cases with early-stage non-small cell lung cancer were chosen for this study. The occurrence of RP+ was predicted using a support vector machine (SVM) model trained with the combined features of the BN-based signature extracted from planning computed tomography (pCT) images and a pretreatment biomarker, serum Krebs von den Lungen-6 (BN+KL-6 model). In all, 242 (20 RP+ and 222 RP-(grade 1)) and 30 cases (8 RP+ and 22 RP-) were used for training and testing the model, respectively. The BN-based features were extracted from BN maps that characterize topologically invariant heterogeneous traits of potential RP+ lung regions on pCT images by applying histogram- and texture-based feature calculations to the maps. The SVM models were built to predict RP+ patients with a BN signature that was constructed based on the least absolute shrinkage and selection operator logistic regression model. The evaluation of the prediction models was performed based on the area under the receiver operating characteristic curves (AUCs) and accuracy in the test. The performance of the BN+KL-6 model was compared to the performance based on the BN, conventional original pCT, and wavelet decomposition (WD) models. RESULTS: The test AUCs obtained for the BN+KL-6, BN, pCT, and WD models were 0.825, 0.807, 0.642, and 0.545, respectively. The accuracies of the BN+KL-6, BN, pCT, and WD models were found to be 0.724, 0.708, 0.591, and 0.534, respectively. CONCLUSION: This study demonstrated the comprehensive performance of the BN+KL-6 model for the prediction of potential RP+ patients before SABR for lung cancer.

Photobiomodulation Therapy to Mitigate Radiation Fibrosis Syndrome.

Objective: We evaluated the role of photobiomodulation (PBM) in radiation fibrosis syndrome (RFS). Background: Radiation therapy (RT) is an important treatment utilized in over half of newly diagnosed cancers. Despite its benefits, patients treated with RT may experience acute and chronic significant side effects depending on both treatment- and patient-related factors. RFS is an important long-term side effect of RT, which can adversely impact patient's quality of life and organ function. With improved oncologic outcomes and survival for cancer patients after radiation, there is an unmet need to address long-term side effects of RT, particularly RFS. Results: Photobiomodulation (PBM) using low energy, nonionizing light primarily in the visible (especially red) or near-infrared spectrum has been demonstrated to decrease acute side effects of radiation in rigorously conducted phase III randomized studies; however, its potential benefit in ameliorating chronic radiation side effects, particularly RFS remains to be investigated. Conclusions: This review summarizes the in vitro data, preclinical animal studies and clinical reports, which showcase the potential benefits of PBM treatments in preventing and reversing RFS.

Enhanced survival from radiation pneumonitis by combined irradiation to the skin.

PURPOSE: To develop mitigators for combined irradiation to the lung and skin. METHODS: Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI); (2) 30 Gy soft X-rays to 10% area of the skin only; (3) 12.5 or 13 Gy WTI + 30 Gy skin irradiation after 3 hours; (4) 12.5 Gy WTI + skin irradiation and treated with captopril (160 mg/m(2)/day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI. RESULTS: After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p < 0.0001). Collagen content was increased at 210 days after 13 Gy WTI vs. 13 Gy WTI + 30 Gy skin irradiation (p < 0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI + 30 Gy skin irradiation (p = 0.008). CONCLUSIONS: Radiation to the skin given 3 h after WTI mitigated morbidity during pneumonitis in rats. Captopril enhanced the rate of healing of radiation-dermatitis after combined irradiations to the thorax and skin.

A possible prevention strategy of radiation pneumonitis: combine radiotherapy with aerosol inhalation of hydrogen-rich solution.

Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).

Helical tomotherapy for solitary lung tumor: feasibility study and dosimetric evaluation of treatment plans.

The purpose of this study is to evaluate the feasibility of and treatment plans for helical tomotherapy (HT) for solitary lung tumors. Nine patients with stage IA non-small-cell lung cancer (NSCLC) and three patients with solitary lung metastasis were treated with HT. All patients were immobilized with the BodyFIX system, and the target volume shown on computed tomography in the 3 respiration phases were superimposed onto the 3-dimensional radiation treatment planning system to represent the internal target motion. All patients were treated with 54-60 Gy in 12 fractions over 8 to 13 days. The median follow-up time was 14 months (range: 3-16 months). The overall response rate was 92%. The local control rate at 1 year was 100% with no difference between NSCLC and metastasis. Of 12 patients, one patient experienced Grade 2 radiation pneumonitis (RP), and the other patient with severe interstitial pneumonia and emphysema experienced Grade 5 RP. The mean lung dose (MLD) and the dose-volume histogram (DVH) for the normal lung volumes were converted into normalized total dose with an alpha/beta ratio of 3 Gy. The DVH of the normal lung volumes demonstrated that the mean volumes of V(10), V(30), V(50), and V(70) were 40.4 +/- 9.4%, 21.3 +/- 6.4%, and 12.8 +/- 4.6%, and 9.3 +/- 4.2% in all patients, 28.8%, 18.7%, 12.3%, and 10.5% in the patient with Grade 2 RP, and 29.3%, 17.9%, 7.7%, and 5.4% in the patient with Grade 5 RP. The mean MLD of all patients was 13.5 +/- 3.9 Gy, and those values of patients with Grade 2 and 5 RP were 12.9 and 21.8 Gy, respectively. Our study found that only the MLD was significantly correlated with RP >Grade 2 (p = 0.030) using the Student's t-test. Our study found the conformity index value of 1.48 +/- 0.15 and the homogeneity index value of 1.066 +/- 0.023, which suggested the feasibility of using HT to treat lung tumors with hypofractionation. In conclusion, HT is a feasible non-invasive technique for treating solitary lung tumors and achieves high accuracy in terms of dose conformity and homogeneity. The decision of the indications for HT might be required caution in cases in which a severe pulmonary toxicity is predicted from the high MLD, especially in cases involving a severe pulmonary comorbidity.