Proton and carbon ion radiotherapy for operable early-stage lung cancer; a prospective nationwide registry.

BACKGROUND AND PURPOSE: To investigate the toxicity and survival outcomes of proton and carbon ion radiotherapy for patients with operable early-stage lung cancer who are eligible for lobectomy. MATERIALS AND METHODS: This multicenter nationwide prospective cohort study included patients with operable early-stage lung cancer. Proton and carbon ion radiotherapy was performed according to the schedule stipulated in the unified treatment policy. Progression-free survival (PFS), overall survival (OS) and treatment-related toxicities were evaluated. RESULTS: A total of 274 patients were enrolled and included in efficacy and safety analyses. The most common tumor type was adenocarcinoma (44 %), while 105 cases (38 %) were not histologically confirmed or diagnosed clinically. Overall, 250 (91 %) of the 274 patients had tumors that were peripherally situated, while 138 (50 %) and 136 (50 %) patients were treated by proton and carbon ion radiotherapy, respectively. The median follow-up time for all censored patients was 42.8 months (IQR 36.7-49.0). Grade 3 or severe treatment-related toxicity was observed in 4 cases (1.5 %). Three-year PFS was 80.5 % (95 % CI: 75.7 %-85.5 %) and OS was 92.5 % (95 % CI: 89.3 %-95.8 %). Pathological confirmation and clinical stage were factors significantly associated with PFS, while tumor location and particle-ion type were not. Meanwhile, clinical stage was significantly associated with OS, but pathological confirmation, tumor location, and particle-ion type were not. CONCLUSIONS: Particle therapy for operable early-stage lung cancer resulted in excellent 3-year OS and PFS in each subset. In this disease context, proton and carbon ion beam therapies are feasible alternatives to curative surgery.

Salvage robot-assisted radical prostatectomy after carbon ion radiotherapy to the prostate.

PURPOSE: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. METHODS: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. RESULTS: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135-226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. CONCLUSIONS: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG).

INTRODUCTION: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. METHODS: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. RESULTS: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. CONCLUSIONS: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

Combination of Clinical Factors and Radiomics Can Predict Local Recurrence and Metastasis After Stereotactic Body Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: Radiomics, which links radiological image features with patient prognoses, is expected to be applied for the prediction of the clinical outcomes of radiotherapy. We investigated the clinical and radiomic factors associated with recurrence patterns after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with histologically confirmed NSCLC who underwent SBRT between April 2003 and June 2017 at our institution. A radiomic score was calculated from five radiomics features (histogram and texture features) selected using the LASSO Cox regression model. These features were extracted from the gross tumor volume (GTV) in three-dimensional wavelet decomposition CT images. We used univariate and multivariate analyses to determine the associations between local control (LC) time and metastasis-free survival (MFS), clinical factors (age, sex, performance status, operability, smoking, histology, and tumor diameter), and the radiomic score. RESULTS: With a median follow-up of 37 months, the following 3-year rates were observed: overall survival, 80.9%; progression-free survival, 61.7%; LC, 75.1%, and MFS; 74.5%. In multivariate analysis, histology (squamous cell carcinoma vs. non-squamous cell carcinoma, p=0.0045), tumor diameter (>3 cm vs. ≤3 cm, p=0.039); and radiomic score (>0.043 vs. ≤0.043, p=0.042) were significantly associated with LC, and the radiomic score (>0.304 vs. ≤0.304, p<0.001) was significantly associated with MFS. CONCLUSION: Histology, tumor diameter, and radiomic score could be significant factors for predicting NSCLC recurrence patterns after SBRT.

The impact of the COVID-19 pandemic on radiotherapy delivery in Japan: An observational study based on the national database.

BACKGROUND: This study analyzed the impact of the coronavirus disease 2019 (COVID-19) pandemic on radiotherapy delivery in Japan using a high-quality Japanese national database based on universal health coverage. METHODS: We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID-19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID-19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture. RESULTS: The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (-5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (-4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single-fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID-19 cases. CONCLUSIONS: Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID-19 cases.

Difference in target dose distributions between Acuros XB and collapsed cone convolution/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy for lung cancer.

Objectives: The objective of the study is to analyze the difference in target dose distributions between Acuros XB (AXB) and collapsed cone convolution (CCC)/superposition and the impact of the tumor locations in clinical cases of stereotactic ablative body radiotherapy (SABR) for lung cancer. Materials and Methods: Ninety-six patients underwent SABR for lung cancers Kyushu University Hospital from 2014 to 2017. We recalculated clinical plans originally calculated by AXB using CCC with the identical monitor units (MUs) and beam arrangements. We calculated the following dosimetric parameters: maximum dose (Dmax), minimum dose (Dmin), homogeneity index (HI), conformity index (CI), and D95 of the planning target volume (PTV). We investigated the difference between the results of two calculations and examined the impact of tumor location. Moreover, we determined the target central dose using a thorax phantom and assessed the calculation accuracy of the two algorithms for each fraction. Results: CCC significantly overestimated the dose to PTV, compared to AXB (P < 0.05). The mean differences of Dmax, Dmin, and D95 were 1.17, 1.95, and 1.85 Gy, respectively. The mean differences of HI and CI were 0.02 and - 0.06. Dmin, HI, and D95 had significant correlations with the tumor location, and the difference was greater when the PTV was included the chest wall (P < 0.05). The discrepancy between the calculated and irradiated dose was 2.48% for CCC, whereas it was 0.14% for AXB. Conclusions: We demonstrated that CCC significantly overestimated the dose to PTV relative to AXB in clinical cases of lung SABR.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Deep learning model fusion improves lung tumor segmentation accuracy across variable training-to-test dataset ratios.

This study aimed to investigate the robustness of a deep learning (DL) fusion model for low training-to-test ratio (TTR) datasets in the segmentation of gross tumor volumes (GTVs) in three-dimensional planning computed tomography (CT) images for lung cancer stereotactic body radiotherapy (SBRT). A total of 192 patients with lung cancer (solid tumor, 118; part-solid tumor, 53; ground-glass opacity, 21) who underwent SBRT were included in this study. Regions of interest in the GTVs were cropped based on GTV centroids from planning CT images. Three DL models, 3D U-Net, V-Net, and dense V-Net, were trained to segment the GTV regions. Nine fusion models were constructed with logical AND, logical OR, and voting of the two or three outputs of the three DL models. TTR was defined as the ratio of the number of cases in a training dataset to that in a test dataset. The Dice similarity coefficients (DSCs) and Hausdorff distance (HD) of the 12 models were assessed with TTRs of 1.00 (training data: validation data: test data = 40:20:40), 0.791 (35:20:45), 0.531 (31:10:59), 0.291 (20:10:70), and 0.116 (10:5:85). The voting fusion model achieved the highest DSCs of 0.829 to 0.798 for all TTRs among the 12 models, whereas the other models showed DSCs of 0.818 to 0.804 for a TTR of 1.00 and 0.788 to 0.742 for a TTR of 0.116, and an HD of 5.40 ± 3.00 to 6.07 ± 3.26 mm better than any single DL models. The findings suggest that the proposed voting fusion model is a robust approach for low TTR datasets in segmenting GTVs in planning CT images of lung cancer SBRT.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.

Clinical results of carbon-ion radiotherapy for stage I non-small cell lung cancer with concomitant interstitial lung disease: a Japanese national registry study (J-CROS-LUNG).

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5-58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Clinical results of carbon ion radiotherapy for inoperable stage I non-small cell lung cancer: A Japanese national registry study (J-CROS-LUNG).

BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for inoperable stage I non-small cell lung cancer (NSCLC), and carbon-ion radiation therapy (CIRT) may be used for such treatment. Although CIRT for stage I NSCLC has demonstrated favorable outcomes in previous reports, the reports covered only single-institution studies. We conducted a prospective nationwide registry study including all CIRT institutions in Japan. MATERIALS AND METHODS: Ninety-five patients with inoperable stage I NSCLC were treated by CIRT between May 2016 and June 2018. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. RESULTS: The median patient age was 77 years. Comorbidity rates for chronic obstructive pulmonary disease and interstitial pneumonia were 43% and 26%, respectively. The most common schedule for CIRT was 60 Gy (relative biological effectiveness (RBE)) in four fractions, and the second most common was 50 Gy (RBE) in one fraction. The 3-year overall survival, cause-specific survival, and local control rates were 59.3%, 77.1%, and 87.3%, respectively. Female sex and ECOG performance status of 0-1 were favorable prognostic factors for overall survival in a multivariate analysis. No grade 4 or higher adverse event was observed. The 3-year cumulative incidence of grade 2 or higher radiation pneumonitis was 3.2%. The risk factors for grade 2 or higher radiation pneumonitis were a force expiratory volume in 1 second (FEV1) of <0.9 L and a total does of ≥ 67 Gy(RBE). CONCLUSION: This study provides real-world treatment outcomes of CIRT for inoperable. stage I NSCLC in Japan.

Establishing quality indicators to comprehensively assess quality assurance and patient safety in radiotherapy and their relationship with an institution's background.

BACKGROUND AND PURPOSE: Quality indicators (QIs) for radiotherapy have been proposed by several groups, but no study has been conducted to correlate the implementation of indicators specific to patient safety over the course of the clinical process with an institution's background. An initial large-scale survey was conducted to understand the implementation status of QIs established for quality assurance and patient safety in radiotherapy and the relationship between implementation status and an institutions' background. MATERIALS AND METHOD: Overall, 68 QIs that were established by this research team after a pilot survey were used to assess structures and processes for quality assurance and patient safety. Data on the implementation of QIs and the institutions' backgrounds were obtained from designated cancer care hospitals in Japan. RESULTS: Overall, 284 institutions (72 %) responded and had a median QI achievement rate of 60.8 %. QIs with low implementation rates, such as the implementation of an error reporting system and establishment of a quality assurance department, were identified. The QI achievement rate and scale of the institution were positively correlated, and the achievement rate of all QIs was significantly higher (p < 0.001) in institutions capable of advanced treatments, such as intensity-modulated radiotherapy, and those with a quality assurance department. CONCLUSION: A large-scale survey on QIs revealed their implementation and relationship with a facility's background. QIs that require improvement were identified, and that these QIs might be effective in providing advanced medical care to many patients.

The impact of the COVID-19 pandemic on radiotherapy in Japan: nationwide surveys from May 2020 through June 2021.

A longitudinal online questionnaire survey on the impact of coronavirus disease 2019 (COVID-19) on the operation of radiotherapy departments in Japan was conducted. Approximately 26.1-70.9% of the radiotherapy departments participated, and their responses were collected in May, July and November 2020, and February and June 2021. The survey results revealed that while the number of patients receiving radiotherapy decreased in 41.2% and 30.7% of institutions in May 2020 and June 2021, respectively, it increased in 4% and 16.8% of institutions in May 2020 and June 2021, respectively. There were a few institutions limiting or postponing patient treatments in June 2021. The hypofractionated regimen was used more during the pandemic than during the pre-pandemic period, particularly for the treatment of breast and prostate cancers as well as for palliation. Infection control measures for patients and staff were followed. Approximately 20% of the respondent institutions had cases of patients with COVID-19 infection receiving radiotherapy. Most institutions encountered challenges in the continuous provision of radiotherapy for patients with COVID-19. In conclusion, COVID-19 had a multifaceted impact on the operations of radiotherapy departments in Japan. Further follow-up and analysis are warranted to understand the long-term impact of COVID-19 on radiotherapy.

Relapse predictability of topological signature on pretreatment planning CT images of stage I non-small cell lung cancer patients before treatment with stereotactic ablative radiotherapy.

BACKGROUND: This study aimed to explore the predictability of topological signatures linked to the locoregional relapse (LRR) and distant metastasis (DM) on pretreatment planning computed tomography images of stage I non-small cell lung cancer (NSCLC) patients before treatment with stereotactic ablative radiotherapy (SABR). METHODS: We divided 125 primary stage I NSCLC patients (LRR: 34, DM: 22) into training (n = 60) and test datasets (n = 65), and the training dataset was augmented to 260 cases using a synthetic minority oversampling technique. The relapse predictabilities of the conventional wavelet-based features (WF), topology-based features [BF, Betti number (BN) map features; iBF, inverted BN map features], and their combined features (BWF, iBWF) were compared. The patients were stratified into high-risk and low-risk groups using the medians of the radiomics scores in the training dataset. RESULTS: For the LRR in the test, the iBF, iBWF, and WF showed statistically significant differences (p < 0.05), and the highest nLPC was obtained for the iBF. For the DM in the test, the iBWF showed a significant difference and the highest nLPC. CONCLUSION: The iBF indicated the potential of improving the LRR and DM prediction of stage I NSCLC patients prior to undergoing SABR.

Multicenter study of re-irradiation using carbon-ions for head and neck malignancies after photon radiotherapy.

PURPOSE: The goal of this multicenter retrospective study of patients with head and neck malignancies was to evaluate the efficacy and safety of carbon-ion (C-ion) radiotherapy (RT) after photon RT. METHODS: We enrolled 56 patients with head and neck malignancies who underwent re-irradiation (re-RT) using C-ions between November 2003 and March 2019, treated previously with photon RT. The tumors at re-RT were located in the sinonasal cavities (n = 20, 35.7%), skull base (n = 12, 21.4%), and orbit (n = 7, 12.5%). The tumors at the initial RT were located in the sinonasal cavities (n = 13, 23.2%), skull base (n = 9, 16.1%), and orbit (n = 9, 16.1%). The median period between the initial RT and re-RT was 41 (4-568) months. The most common histology of re-RT was squamous cell carcinoma (n = 11, 19.6%). The most commonly used protocol was 57.6 Gy (relative biological effectiveness) in 16 fractions (n = 23, 41.1%). Surgery preceded re-RT in three patients (5.4%). One patient with malignant melanoma received concurrent chemotherapy. RESULTS: The 2-year local control, progression-free survival, and overall survival rates were 66.5%, 36.9%, and 67.9%, respectively. The median follow-up time was 28 months. Two patients (3.6%) developed grade ≥ 3 acute toxicities, and 14 (25.0%) developed grade ≥ 3 late toxicities. A single patient had confirmed grade 5 dermatitis with infection. CONCLUSION: Re-RT using C-ions for head and neck malignancies after photon RT is an effective treatment with tolerable toxicity.

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.

An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy.

INTRODUCTION: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. METHODS: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). RESULTS: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. CONCLUSION: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

Impact of pre-treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: a supplementary analysis of the Japan Clinical Oncology Group study JCOG0403.

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray's test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3-4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher's exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC.

The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.

Multicenter Study of Carbon-ion Radiotherapy for Oropharyngeal Non-squamous Cell Carcinoma.

BACKGROUND/AIM: To evaluate treatment outcomes of carbon-ion radiotherapy for oropharyngeal non-squamous cell carcinoma at four carbon-ion facilities in Japan. PATIENTS AND METHODS: We retrospectively analyzed the cases of 33 patients with oropharyngeal non-squamous cell carcinoma who were treated with carbon-ion radiotherapy between November 2003 and December 2014. RESULTS: The histology included adenoid cystic carcinoma (n=25) and mucosal malignant melanoma (n=4). No patients had T1 tumors; 23 had T4 tumors. The most-commonly prescribed dose was 57.6 Gy (RBE) in 16 fractions. The median follow-up period was 34.8 months (range=4.2-122.8 months). The 3-year local control and overall survival rates were 94.7% and 90.7%, respectively. There were no grade ≥4 acute adverse events. Only one patient experienced a grade ≥4 late adverse event. No patients experienced late adverse events related to swallowing or salivary function. CONCLUSION: Carbon-ion radiotherapy appears to be a promising treatment option for oropharyngeal non-squamous cell carcinoma.