Novel concept of "sequential particle radiotherapy" with atezolizumab plus bevacizumab for hepatocellular carcinoma with portal vein tumor thrombus.

Owing to the high objective response rate of atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC), the concept of sequential conversion to local treatment has recently become mainstream. The conversion concept is mainly applied to Barcelona Clinic for Liver Cancer (BCLC) stage B cases, and radiotherapy is rarely considered as a conversion local treatment. We herein report three patients who were treated with the novel concept of "sequential particle radiotherapy," consisting of Atez/Bev therapy followed by particle radiotherapy (PRT) for HCC with advanced portal vein tumor thrombus (Vp3/4 PVTT). All patients achieved partial response radiologically and were switched to PRT. All patients were recurrence free at 1 year after the introduction of Atez/Bev therapy without any additional treatment. This upcoming combination strategy includes the advocacy of sequential concepts for BCLC stage C cases and the introduction of PRT as a local treatment after Atez/Bev.

Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageals cell carcinoma: a multi-center retrospective Japanese cohort study.

BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.

Space-Making Particle Therapy for Unresectable Hilar Cholangiocarcinoma.

INTRODUCTION: Although the primary treatment option for hilar cholangiocarcinoma (HC) has been surgical resection, most patients present with unresectable advanced tumors at the time of diagnosis. Particle therapy (PT) holds great potential for HC, even though the anatomical proximity to the gastrointestinal tract prevents delivering a radical dose to the tumor. Space-making PT (SMPT), consisting of spacer placement surgery and subsequent PT, has been developed to minimize complications and maximize the therapeutic benefit of dose escalation for HC. This study aimed to conduct a dosimetric evaluation and examine the effectiveness of SMPT for the treatment of HC. METHODS: Between 2007 and 2018, 12 patients with unresectable HC treated with SMPT were enrolled. The treatment outcomes and effectiveness of spacer placement surgery were evaluated through analyses of pre- and post-surgical parameters of dose-volume histograms. RESULTS: All patients completed the planned SMPT protocol. The median survival time was 29.6 months, and the 1- and 3-year overall survival rates were 82.5% and 45.8%, respectively. The mean V95% value (volume irradiated with 95% of the planned treatment dose) of the gross tumor volume and clinical target volume after spacer placement surgery improved to 98.5% and 96.6% from preoperative values of 85.6% and 78.1%, respectively (p = 0.0196 and p = 0.0053, respectively). Grade 3 or higher adverse events after SMPT were seen in 6 patients. DISCUSSION/CONCLUSION: SMPT led to improvements in dosimetric parameters and showed good feasibility and excellent outcomes. SMPT can be a promising novel alternative for unresectable HC.

Proton Radiotherapy for Isolated Local Recurrence of Primary Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The optimal treatment for isolated local recurrence (ILR) of pancreatic adenocarcinoma (PDAC) after surgical resection remains unclear. This study aimed to evaluate the safety and efficacy of proton radiotherapy (PRT) for ILR of PDAC after surgery. METHODS: The medical records of patients with ILR of PDAC after surgery who underwent proton beam therapy between 2011 and 2015 at Hyogo Ion Beam Medical Center were retrospectively studied. RESULTS: The study analyzed 30 patients (14 women and 16 men) with a median age of 65 years (range 38-81 years) who had initially undergone pancreatoduodenectomy (n = 23) or distal pancreatectomy (n = 7) for their primary tumors. Upon ILR, PRT was administered with a median total cumulative dose of 67.5 gray equivalent (GyE) (range 50-67.5 GyE) using 19 to 25 fractions. For 25 patients, concurrent chemotherapy was administered using gemcitabine (n = 18) or S-1 (n = 7). Four patients (13.3%) experienced acute grade ≥ 3 gastrointestinal toxicities. After a median follow-up period of 17.6 months (range 2.1-50.4 months), 23 patients had experienced tumor progression and 10 had died. Nine patients (30%) experienced local tumor progression. The median overall, progression-free, and local progression-free survival rates were 26.1, 12.3, and 41.2 months, respectively. Pre-PRT serum levels of cancer antigen 19-9 higher than 100 U/mL and duke pancreatic monoclonal antigen type 2 higher than 150 U/mL were significantly associated with shorter progression-free survival rates. CONCLUSIONS: Proton radiotherapy for ILR of PDAC after surgery is well tolerated and produces good locoregional control and should be considered for eligible patients.

Radiotherapy for vaginal cancer: a multi-institutional survey study of the Japanese Radiation Oncology Study Group.

PURPOSE: Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. MATERIALS AND METHODS: RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. RESULTS: A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). CONCLUSIONS: Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.

Patterns of failure after postoperative intensity-modulated radiotherapy for locally advanced and recurrent head and neck cancer.

OBJECTIVE: To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy. METHODS: A retrospective chart review was performed. RESULTS: Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25-115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of <5%, except for mucositis. No severe toxicities associated with the flap reconstruction were observed either. CONCLUSION: Postoperative intensity-modulated radiotherapy appears to be effective and feasible for patients with head and neck squamous cell carcinoma.

Patterns of practice in the radiation therapy for bladder cancer: survey of the Japanese Radiation Oncology Study Group (JROSG).

OBJECTIVE: To retrospectively analyze the clinical outcomes of radiation therapy with or without chemotherapy for bladder cancer in Japan. METHODS: A questionnaire-based survey of patients with pathologically proven bladder cancer treated by definitive radiation therapy between 2002 and 2006 was conducted by the Japanese Radiation Oncology Study Group, and the clinical records of 159 patients were collected from 17 institutions. Concurrent intra-arterial chemoradiotherapy and concurrent systemic chemoradiotherapy were administered in 51 and 33 patients, respectively. RESULTS: The 5-year overall survival and bladder preservation rates were 48 and 39%, respectively. Eighty-nine (56%) patients developed recurrence (bladder, 48; regional lymph nodes, 4; distant sites, 41). The results of multivariate analysis revealed that adoption of chemotherapy was the only significant prognostic factor for overall survival (relative risk = 0.615 [95% confidence interval: 0.439-0.862], P = 0.005). The type of chemotherapy administered did not significantly affect the local control or overall survival rates. The actuarial 5-year overall survival rates and bladder preservation in the radiation therapy combined with intra-arterial chemotherapy group were 64 and 58%, respectively, and the corresponding rates in the radiation therapy combined with systemic chemotherapy group were 67 and 42%, respectively. CONCLUSIONS: The results of this survey revealed the current status of practice of radiation therapy for bladder cancer in Japan. A multi-institutional prospective study is needed based on the results of this study to determine the optimal radiotherapeutic approach, including the need for concurrent chemotherapy and the appropriate chemotherapy regimen for invasive bladder cancer.

Primary CNS lymphoma treated with radiotherapy in Japan: a survey of patients treated in 2005-2009 and a comparison with those treated in 1985-2004.

BACKGROUND: The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995-2004 and those on 466 patients treated during the period 1985-1994. RESULTS: In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995-2004 period, significant changes in the 2005-2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009 periods, respectively, but relapse-free survival did not improve between the 1995-2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. CONCLUSIONS: Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

Dose-volume comparisons of proton therapy for pencil beam scanning with and without multi-leaf collimator and passive scattering in patients with lung cancer.

This study evaluated the dose distributions of proton pencil beam scanning (PBS) with/without a multileaf collimator (MLC) compared to passive scattering (PS) for stage I/II lung cancers. Collimated/uncollimated (PBS+/PBS-) and PS plans were created for 20 patients. Internal-clinical-target-volumes (ICTVs) and planning-target-volumes (PTVs) with a 5 mm margin were defined on the gated CTs. Organs-at-risk (OARs) are defined as the normal lungs, spinal cord, esophagus, and heart. The prescribed dose was 66 Gy relative-biological-effectiveness (RBE) in 10 fractions at the isocenter and 50% volume of the ICTVs for the PS and PBS, respectively. We compared the target and OAR dose statistics from the dose volume histograms. The PBS+ group had a significantly better mean PTV conformity index than the PBS- and PS groups. The mean dose sparing for PBS+ was better than those for PBS- and PS. Only the normal lung doses of PBS- were worse than those of PS. The overall performance of the OAR sparing was in the order of PBS+, PBS-, and PS. The PBS+ plan showed significantly better target homogeneity and OAR sparing than the PBS- and PS plans. PBS requires collimating systems to treat lung cancers with the most OAR sparing while maintaining the target coverage.

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.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

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 patiets 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.

Hepatic Resection vs Particle Therapy as an Initial Treatment for Single Hepatocellular Carcinoma: Bi-institutional Propensity Score-Matched Analysis.

BACKGROUND: Curative treatment for hepatocellular carcinoma (HCC) is limited to hepatic resection (HR), radiofrequency ablation, and liver transplantation, but the value of particle therapy (PT) as an initial treatment remains unclear. This study aimed to compare the outcomes of HR and PT for single HCC. STUDY DESIGN: A total of 554 patients with single HCC without vascular invasion were enrolled from January 2000 to December 2015. Patients underwent either HR (n = 279) or PT (n = 275) as initial treatments. A one-to-one propensity score-matching analysis was performed to evaluate the overall survival (OS) and progression-free survival after dividing patients according to liver function as assessed by the modified albumin-bilirubin grade. RESULTS: The median OS (130 vs 85 months, p = 0.001) and progression-free survival (47 vs 30 months HR, p = 0.004) of HR were also significantly better than that of PT in the propensity score-matching cohort with modified albumin-bilirubin grade 1/2a (n = 145 per group). Meanwhile, in a propensity score-matching cohort with modified albumin-bilirubin grade 2b/3 (n = 53 per group), there were no significant differences in median OS and progression-free survival between HR and PT. CONCLUSIONS: HR may be preferable as an initial treatment for patients with single HCC without vascular invasion, especially those with preserved liver function. PT can be an acceptable alternative to HR for patients without surgical indication and/or impaired liver function.

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.

Clinical impact of spacer placement surgery with expanded polytetrafluoroethylene sheet for particle therapy.

BACKGROUND: Spacer placement surgery is useful in particle therapy (PT) for patients with abdominopelvic malignant tumors located adjacent to the gastrointestinal tract. This study aimed to assess the safety, efficacy, and long-term outcomes of spacer placement surgery using an expanded polytetrafluoroethylene (ePTFE) spacer. METHODS: This study included 131 patients who underwent ePTFE spacer placement surgery and subsequent PT between September 2006 and June 2019. The overall survival (OS) and local control (LC) rates were calculated using Kaplan-Meier method. Spacer-related complications were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: The median follow-up period after spacer placement surgery was 36.8 months. The 3-year estimated OS and LC rates were 60.5% and 76.5%, respectively. A total of 130 patients (99.2%) were able to complete PT. Spacer-related complications of ≥ grade 3 were observed in four patients (3.1%) in the acute phase and 13 patients (9.9%) in the late phase. Ten patients (7.6%) required removal of the ePTFE spacer. CONCLUSIONS: Spacer placement surgery using an ePTFE spacer for abdominopelvic malignant tumors is technically feasible and acceptable for subsequent PT. However, severe spacer-related late complications were observed in some patients. Since long-term placement of a non-absorbable ePTFE spacer is associated with risks for morbidity and infection, careful long-term follow-up and prompt therapeutic intervention are essential when complications associated with the ePTFE spacer occur. TRIAL REGISTRATION: retrospectively registered.

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.

Proton radiotherapy as a treatment strategy to increase survival in locally advanced pancreatic cancer in the body and tail: a retrospective study.

BACKGROUND: Long-term outcomes and prognostic factors of proton radiotherapy for locally advanced pancreatic cancer (LAPC) in the body and tail are still unknown. The aim of this study was to determine the prognostic factors after proton radiotherapy in a large group of patients with LAPC in the body and tail. METHODS: The medical records of 200 patients with LAPC in the body and tail who underwent proton radiotherapy between February 2009 and January 2021 at the Hyogo Ion Beam Medical Center were retrospectively reviewed to identify prognostic factors that contribute to long-term survival. RESULTS: The overall survival rate at 1- and 2-year after PT was 69.6% and 35.4% with a median overall survival of 18.4 months. The 1- and 2-year local progression-free, and progression-free survival rates were 84.3% and 68.0%, and 44.3% and 19.4%, respectively. In multivariate analysis, superior mesenteric artery (SMA) invasion (SMA only invasion vs. celiac artery only invasion; P = 0.049: SMA and celiac artery invasion vs. celiac artery only invasion; P = 0.017), carbohydrate antigen 19-9 (CA 19-9) level ≥ 231.9 U/mL (P = 0.001), anterior peripancreatic invasion (P = 0.006), and incomplete scheduled concurrent chemotherapy (P = 0.009) were statistically significant prognostic factors for overall survival. There was no significant difference in local progression-free survival; however, distant metastasis-free survival was statistically worse in patients with prognostic factors than in those without. CONCLUSIONS: Proton radiotherapy for LAPC in the body and tail may be a valuable multidisciplinary treatment option. Patients with SMA invasion, higher pre-proton radiotherapy serum CA 19-9 level, anterior peripancreatic invasion, or incomplete scheduled concurrent chemotherapy had worse overall survival because of worse distant metastasis-free survival, suggesting that distant metastases have a significant impact on overall survival in such patients. TRIAL REGISTRATION: Retrospectively registered.

Analysis of particle therapy registries based on a unified treatment policy for esophageal cancer.

This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41-88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76-1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.

Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy for non-metastatic locally advanced pancreatic cancer: a single-center retrospective study.

BACKGROUND: Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC. METHODS: The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes. RESULTS: The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P < 0.001). LAPCs with anterior peripancreatic invasion had more peritoneal recurrence within 6 months after GTP than those without anterior peripancreatic invasion (P = 0.039). CONCLUSIONS: GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.