Feasibility of carbon-ion radiotherapy for re-irradiation of locoregionally recurrent, metastatic, or secondary lung tumors.

Intrathoracic recurrence after carbon-ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer-related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re-irradiation with carbon-ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon-ion radiotherapy who were treated with re-irradiation with carbon-ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy-three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon-ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re-irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow-up period after re-irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2-year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re-irradiation with carbon-ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re-irradiation with carbon-ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors

Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: worst case analysis in lung and liver treatments

Introduction: We evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment.\nMethods & Materials: 4DCT was performed in20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60Gy(RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT.\nResults: For liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6±0.5% and 89.8±0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6±14.0% and 46.3±26.7%, respectively. Dose assessment results for lung cases were 84.8±12.8% and 58.0±24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1±1.5% and 87.0±2.2%, respectively.\nConclusions: 4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some case

Carbon-ion pencil beam scanning for thoracic treatment - initiation report and dose metrics evaluation.

Carbon-ion beam scanning has not previously been used for moving tumor treatments. We have commenced respiratory-gated carbon-ion radiotherapy (CIRT) in the thoracic and abdominal regions under free-breathing conditions as a clinical trial. This study aimed to investigate this treatment in the lungs in comparison with passive scattering CIRT. Five patients had thoracic tumors treated with carbon-ion scanned beams using respiratory gating. We analyzed the actual treatments and calculated passive scattering treatment plans based on the same planning CT. We evaluated tumor size until 3 months post treatment and each treatment plan regarding dose delivered to 95% of the clinical target volume (CTV-D95), mean lung dose, percentage of lung receiving at least 5 Gy (RBE) (Lung-V5), Lung-V10, Lung-V20, heart maximum dose (Dmax), esophagus Dmax, cord Dmax and skin Dmax. Obvious tumor deterioration was not observed up to 3 months post treatment. The dose evaluation metrics were similar item by item between respiratory-gated scanned CIRT and passive scattering CIRT. In conclusion, scanned beam CIRT provided treatments equivalent to passive scattering CIRT for thoracic tumors. Increased sample numbers and longer-term observation are needed

Carbon-ion re-irradiation for recurrences after initial treatment of stage I non-small cell lung cancer with carbon-ion radiotherapy.

PURPOSE: \nTo investigate carbon-ion radiotherapy (CIRT) for in-field recurrence of stage I non-small cell lung cancer (NSCLC) initially treated with CIRT.\nMATERIALS AND METHODS: \nFrom January 2007 to March 2014, patients initially treated for stage I NSCLC with CIRT and relapsed in-field were candidates. Overall survival (OS) rate, local control (LC) rate, progressive free survival (PFS) rate, dose to the lungs and skin, and adverse effects were analyzed.\nRESULTS: \nTwenty-nine patients were eligible. Median age at re-irradiation was 74years (range 53-90). Median observation period from the first day of re-irradiation was 29months (4-88months). Median prescribed dose was 46.0Gy (RBE) as initial treatment and 66.0Gy (RBE) in 12 fractions as re-irradiation. Two-year OS, LC, and PFS rates after re-irradiation were 69.0% (95% CI: 50.3-83.0), 66.9% (95% CI: 47.5-81.9), and 51.7% (95% CI: 34.1-68.9). Median skin maximum dose was 53.8Gy (RBE) (range 4.4-103.1) and median of mean lung dose was 7.3Gy (RBE) (range 2.6-14.0). There were no severer than grade 2 adverse effects except one (3.4%) grade 3 bacterial pneumonia, which was not considered radiation-induced.\nCONCLUSION: \nCIRT for stage I NSCLC local recurrence is an acceptable definitive re-treatment

Response to "Comment on \u27Objective assessment in digital images of skin erythema

We appreciate the interest of Carrara et al.1 in our recent article on the assessment method in digital images of skin erythema caused by radiotherapy.2 Matsubara et al. presented a linear relationship between skin blood flow and skin dose, while Carrara et al. suggest that their clinical data do not reproduce it even though their sample number of patients treated is ten times larger than that of Matsubara et al. We would like to suggest that the disagreement between the data by Carrara et al. and Matsubara et al. is qualitatively reasonable because it arises from neglecting the recovery process of damaged skin as is explained below. Skin erythema is physiologically caused by expansion of capillaries due to increased blood flow, which is a part of the biological skin repair response. As long as the skin erythema is an acute toxicity, the skin recovers and the symptom usually disappears in several months. This indicates that skin blood flowincreases owing to the repair process just after irradiation, but decreases owing to the recovery process from the damaged skin a few tens of days later. Matsubara et al. treated six patients who had the carbon beam therapy with a total prescription dose of 50 Gy (RBE).2 It should be noted that the prescription dose was delivered by a single fraction from four ports, indicating that the treatment was completed in one day. On the other hand, Carrara et al. treated 61 patients who had the 6/15 MV photon therapy with a total prescription dose of 50 Gy but with a 2 Gy fraction, indicating that the treatment was completed in 25 days. The recovery process for skin erythema is assumed to work during the treatment. This would result in the reduction of skin blood flow per accumulated skin dose, causing nonlinearity between skin blood flow and skin dose. The disagreement between the data by Carrara et al. and Matsubara et al. can be qualitatively understood by taking the recovery process into account. That is why Matsubara et al. selected only the cases of a single fraction in order to avoid the recovery effect. As Carrara et al. suggest, however, we agree that the linearity observed by Matsubara et al. is not based on physical evidence. What Matsubara et al. discussed was just that the gross trend of the obtained data could be expressed by the linear relationship with moderate accuracy, where several variations due to individuality of patient or time dependence of skin erythema were assumed to be negligible as discussed in Ref. 2. There is no known numerical relationship between accumulated skin dose and time dependence of skin erythema. The new data suggested by Carrara et al., therefore, are assumed to be important for further investigation of skin erythema

Prognostic analysis of radiation pneumonitis: carbon-ion radiotherapy in patients with locally advanced lung cancer

Background\nCarbon-ion radiotherapy (CIRT) is a promising treatment for locally advanced non-small-cell lung cancer, especially for patients with inoperable lung cancer. Although the incidence of CIRT-induced radiation pneumonitis (RP) ≥ grade 2 ranges from 2.5 to 9.9%, the association between CIRT-induced RP and dosimetric parameters is not clear. Herein, we identified prognostic factors associated with symptomatic RP after CIRT for patients with non-small-cell lung cancer.\nMethods\nClinical results of 65 patients treated with CIRT between 2000 and 2015 at the National Institute of Radiological Sciences were retrospectively analyzed. Clinical stage II B disease (TNM classification) was the most common stage among the patients (45%). The median radiation dose was 72 Gy (68–76) relative biological effectiveness (RBE) in 16 fractions. In cases involving metastatic lymph nodes, prophylactic irradiation of mediastinal lymph nodes was performed at a median dose of 49.5 Gy (RBE). The median follow-up was 22 months.\nResults\nGrade 2 and grade 3 RP occurred in 6 and 3 patients (9 and 5%), respectively. No patients developed grade 4 or 5 RP. Using univariate analysis, vital capacity as a percentage of predicted (%VC), forced expiratory volume in 1 s (FEV1), mean lung dose (MLD), volume of lung receiving ≥5 Gy (RBE) (V5), V10, V20 and V30 were determined to be the significant predictive factors for ≥ grade 2 RP. The receiver operating characteristic (ROC) analysis revealed the cutoff values for %VC, FEV1, MLD, V5, V10, V20 and V30 for ≥ grade 2 RP, which were 86.9%, 1.16 L, 12.5 Gy (RBE), 28.8, 29.9, 20.1 and 15.0%, respectively. In addition, the multivariate analysis revealed that %VC <86.9% (odds ratio = 13.7; p = 0.0041) and V30 ≥ 15% (odds ratio = 6.1; p = 0.0221) were significant risk factors.\nConclusions\nOur study demonstrated the risk factors for ≥ grade 2 RP after carbon-ion radiotherapy for patients with locally advanced lung cancer