Prognostic analysis of radiation-induced liver damage following carbon-ion radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. METHODS: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child-Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47-95 years), and the median tumor diameter was 41 mm (range 5-160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child-Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3-41.1 months), and RILD was observed in 11 patients (10.1%). RESULTS: Multivariate analysis showed that pretreatment Child-Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child-Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. CONCLUSION: In conclusion, the pretreatment Child-Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC.

Effectiveness of Carbon Ion Radiotherapy for Bone and Soft Tissue Sarcoma in Older Patients.

BACKGROUND/AIM: The aging population is expected to increase the occurrences of bone sarcoma (BS) and soft tissue sarcoma (STS). Carbon ion radiotherapy (CIRT) is reported to be effective for BS and several STSs. However, the effect of CIRT on clinical outcomes, functional prognoses, and quality of life (QOL) in older patients who underwent CIRT has not been reported. Therefore, we aimed to evaluate the effect of CIRT on clinical outcomes, functional prognoses and QOL in older patients with BS or STS. PATIENTS AND METHODS: This retrospective cohort study included 235 patients aged >70 years with BS or STS who underwent CIRT. Overall survival (OS), cancer-specific survival (CSS), and local control (LC) were evaluated in chordoma and non-chordoma patients. Furthermore, factors associated with post-CIRT Toronto Extremity Salvage Score (TESS) and EuroQoL 5-dimension 5-level (EQ-5D-5L) index were assessed. RESULTS: The overall 5-year LC, OS, and CSS rates were 81%, 62%, and 76%, respectively. In the chordoma and non-chordoma groups, the 5-year LC, OS, and CSS rates were 84%, 72%, and 87%; and 77%, 47%, and 60%, respectively. The mean post-CIRT TESS and EQ-5D-5L index were 75% and 0.71, respectively. The TESSs and EQ-5D-5L indices tended to be better among males, younger patients (<76 years old), patients with small tumor volumes, and patients with chordoma. CONCLUSION: CIRT is effective for older patients with BS, especially with chordoma, and STS with good LC and survival rates. Furthermore, post-treatment limb function and QOL were comparable with those of the other treatments and age groups.

Efficacy and toxicity of photon, proton, and carbon ion radiotherapy in the treatment of intracranial solitary fibrous tumor/hemangiopericytoma.

BACKGROUND: Solitary fibrous tumors (SFT) of the central nervous system are rare and treatment options are not well established. The aim of this study was to evaluate the clinical outcomes of radiotherapy (RT) and re-radiotherapy (re-RT) for de novo intracranial SFT and recurrent intracranial SFT. METHODS: This retrospective study analyzed efficacy and toxicity of different RT modalities in patients who received radiotherapy (RT) for intracranial SFT at Heidelberg University Hospital between 2000 and 2020 following initial surgery after de novo diagnosis ("primary group"). We further analyzed the patients of this cohort who suffered from tumor recurrence and received re-RT at our institution ("re-irradiation (re-RT) group"). Median follow-up period was 54.0 months (0-282) in the primary group and 20.5 months (0-72) in the re-RT group. RT modalities included 3D-conformal RT (3D-CRT), intensity-modulated RT (IMRT), stereotactic radiosurgery (SRS), proton RT, and carbon-ion RT (C12-RT). Response rates were analyzed according to RECIST 1.1 criteria. RESULTS: While the primary group consisted of 34 patients (f: 16; m:18), the re-RT group included 12 patients (f: 9; m: 3). Overall response rate (ORR) for the primary group was 38.3% (N = 11), with 32.4% (N = 11) complete remissions (CR) and 5.9% (N = 2) partial remissions (PR). Stable disease (SD) was confirmed in 5.9% (N = 2), while 41.2% (N = 14) experienced progressive disease (PD). 14% (N = 5) were lost to follow up. The re-RT group had 25.0% CR and 17.0% PR with 58.0% PD. The 1-, 3-, and 5-year progression-free survival rates were 100%, 96%, and 86%, respectively, in the primary group, and 81%, 14%, and 14%, respectively, in the re-RT group. Particle irradiation (N = 11) was associated with a lower likelihood of developing a recurrence in the primary setting than photon therapy (N = 18) (OR = 0.038; p = 0.002), as well as doses ≥ 60.0 Gy (N = 15) versus < 60.0 Gy (N = 14) (OR = 0.145; p = 0.027). Risk for tumor recurrence was higher for women than for men (OR = 8.07; p = 0.014) with men having a median PFS of 136.3 months, compared to women with 66.2 months. CONCLUSION: The data suggests RT as an effective treatment option for intracranial SFT, with high LPFS and PFS rates. Radiation doses ≥ 60 Gy could be associated with lower tumor recurrence. Particle therapy may be associated with a lower risk of recurrence in the primary setting, likely due to the feasibility of higher RT-dose application.

Tumor volume instead of recurrent T category predicts clinical outcome of patients with locally recurrent nasopharyngeal carcinoma salvaged by carbon ion radiation therapy.

BACKGROUND: Although carbon ion radiation therapy (CIRT) substantially improves the overall survival (OS) of patients with LR-NPC, approximately 40% of the patients may develop local recurrence. The purpose of study is to assess the value of tumor volume (TV) as a predictive tool to guide individualized CIRT. METHODS: Consecutive patients with LR-NPC treated using CIRT at Shanghai Proton and Heavy Ion Center between April 2015 and May 2019 were included. TV before CIRT was delineated and calculated. The generalized additive Cox model was used to examine the relationship between TV and OS and local progression-free survival (LPFS). A cutoff value of tumor volume was identified to best discriminate patients with different 2-year OS rates, using receiver operating characteristic (ROC) analysis. RESULTS: A total of 157 patients were enrolled. The median tumor volume was 22.49 (2.52-90.13) ml. In the univariable analyses, tumor volume was significantly associated with OS (p < 0.001) and LPFS (p = 0.01). The relationships with OS (p = 0.009) and LPFS (p = 0.020) remained significant in multivariable analyses. Using ROC analysis, a TV of 26.69 ml was identified to predict the 2-year OS rate. To facilitate potential clinical use, 25 ml was designated as the final cutoff value. The 2-year OS and LPFS rates were 88.6 % vs 62.3 %, and 54.7 % vs 35.5 %, for patients with a TV ≤ 25 ml and > 25 ml, respectively. CONCLUSION: Tumor volume could predict the OS and LPFS of patients. We propose that tumor volume should be considered in the risk stratification and CIRT-based treatment for patients with LR-NPC.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

Is motherhood still possible after pelvic carbon ion radiotherapy? A promising combined fertility-preservation approach.

INTRODUCTION: Preserving the endocrine and reproductive function in young female cancer patients undergoing pelvic radiation is a significant challenge. While the photon beam radiation's adverse effects on the uterus and ovaries are well established, the impact of pelvic carbon ion radiotherapy on women's reproductive function is largely unexplored. Strategies such as oocyte cryopreservation and ovarian transposition are commonly recommended for safeguarding future fertility. METHODS: This study presents a pioneering case of successful pregnancy after carbon ion radiotherapy for locally advanced sacral chondrosarcoma. RESULTS: A multidisciplinary approach facilitated the displacement of ovaries and uterus before carbon ion radiotherapy, resulting in the preservation of endocrine and reproductive function. CONCLUSION: The patient achieved optimal oncological response and delivered a healthy infant following the completion of cancer treatment.

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.

Curative carbon ion radiotherapy in a head and neck mucosal melanoma series: Facing the future within multidisciplinarity.

PURPOSE: To evaluate efficacy and toxicity of carbon ion radiotherapy (CIRT) in locally advanced head and neck mucosal melanoma (HNMM) patients treated at our Institute. MATERIALS AND METHODS: Between June 2013 and June 2020, 40 HNMM patients were treated with CIRT. Prescription dose was 65.6-68.8 Gy relative biological effectiveness [RBE] in 16 fractions. Twelve (30%) patients received only biopsy, 28 (70%) surgical resection before CIRT. Immunotherapy was administered before and/or after CIRT in 45% of patients, mainly for distant progression (89%). RESULTS: Median follow-up was 18 months. 2-year Local Relapse Free Survival (LRFS), Overall Survival (OS), Progression Free Survival (PFS) and Distant Metastasis Free Survival (DMFS) were 84.5%, 58.6%, 33.2% and 37.3%, respectively. At univariate analysis, LRFS was significantly better for non-recurrent status, < 2 surgeries before CIRT and treatment started < 9 months from the initial diagnosis, with no significant differences for operated versus unresected patients. After relapse, immunotherapy provided longer median OS (17 months vs 3.6, p-value<0.001). Late toxicity ≥ G3 (graded with CTCAE 5.0 scale) was reported in 10% of patients. CONCLUSION: CIRT in advanced HNMM patients is safe and locally effective. Prospective trials are warranted to assess the role of targeted/immune- systemic therapy to improve OS.

Carbon-Ion Radiation Therapy for Unresectable Locally Recurrent Colorectal Cancer: A Promising Curative Treatment for Both Radiation Therapy: Naïve Cases and Reirradiation Cases.

PURPOSE: It is difficult to effectively cure patients with unresectable locally recurrent colorectal cancers (LRCRCs) using conventional chemotherapy or chemoradiation therapy. Furthermore, treatment options vary depending on the patient's history of radiation therapy. Carbon-ion radiation therapy (CIRT) is a potentially curative treatment for these patients. Here, we compare the treatment outcomes of radiation therapy-naïve cases (nRT) and re-irradiation cases (reRT). METHODS AND MATERIALS: Patients with LRCRC treated with CIRT at QST Hospital between 2003 and 2019 were eligible. CIRT was administered daily 4 d/wk for 16 fractions. The total irradiated dose was set at 73.6 Gy (relative biologic effectiveness-weighted dose [RBE]) for nRT and 70.4 Gy (RBE) for reRT patients. RESULTS: We included 390 nRT cases and 83 reRT cases. The median follow-up period from the initiation of CIRT was 48 (5-208) months. The 3-year overall survival (OS) rates for nRT and reRT were 73% (95% CI, 68%-77%) and 76% (65%-84%), respectively. The 5-year OS rates were 50% (45%-55%) and 50% (38%-61%), respectively. These rates did not differ significantly (P = .55). The 3-year local control (LC) rates for nRT (73.6 Gy) and reRT (70.4 Gy) cases were 80% (75%-84%) and 80% (68%-88%), respectively. The 5-year LC rates were 72% (67%-78%) and 69% (55%-81%), respectively, without a significant difference (P = .56). CONCLUSIONS: Our results suggest that CIRT for LRCRC is a very effective and promising treatment for both nRT and reRT cases.

Dosimetric rationale and preliminary experience in proton plus carbon-ion radiotherapy for esophageal carcinoma: a retrospective analysis.

BACKGROUND: Concurrent chemoradiotherapy has been standard of care for unresectable esophageal carcinoma. There were no reports on proton radiotherapy (PRT) plus carbon-ion radiotherapy (CIRT) with pencil beam scanning (PBS) for esophageal carcinoma. This study evaluated the tolerability and efficiency of proton and sequential carbon-ion boost radiotherapy for esophageal carcinoma. METHODS: From April 2017 to July 2020, 20 patients with primary esophageal carcinoma at stages II-IV were treated with PRT plus sequential CIRT with PBS. A median relative biological effectiveness-weighted PRT dose of 50 Gy in 25 fractions, and a sequential CIRT dose of 21 Gy in 7 fractions were delivered. Respiratory motion management was used if the tumor moved > 5 mm during the breathing cycle. A dosimetric comparison of photon intensity-modulated radiotherapy (IMRT), PRT, and CIRT was performed. The median times and rates of survivals were estimated using the Kaplan-Meier method. Comparison of the dose-volume parameters of the organs at risk employed the Wilcoxon matched-pairs test. RESULTS: Twenty patients (15 men and 5 women, median age 70 years) were included in the analysis. With a median follow-up period of 25.0 months, the 2-year overall survival and progression-free survival rates were 69.2% and 57.4%, respectively. The patients tolerated radiotherapy and chemotherapy well. Grades 1, 2, 3, and 4 acute hematological toxicities were detected in 25%, 30%, 10%, and 30% of patients, respectively. Grades 3-5 acute non-hematological toxicities were not observed. Late toxicity events included grades 1, 2, and 3 in 50%, 20%, and 10% (pulmonary and esophageal toxicity in each) of patients. Grades 4-5 late toxicities were not noted. PRT or CIRT produced lower doses to organs at risk than did photon IMRT, especially the maximum dose delivered to the spinal cord and the mean doses delivered to the lungs and heart. CONCLUSIONS: PRT plus CIRT with PBS appears to be a safe and effective treatment for esophageal carcinoma. PRT and CIRT delivered lower doses to organs at risk than did photon IMRT. Further investigation is warranted.

Efficacy and safety of carbon ion radiotherapy for chordomas: a systematic review and meta-analysis.

OBJECTIVE: Carbon ion radiotherapy (C-ion RT) for chordomas has been gradually performed in several research centres. This study aimed to systematically review the results of clinical reports from these institutions and to evaluate the safety and efficacy of C-ion RT. METHODS: In accordance with the PRISMA guidelines and set search strategies, we searched four databases for articles from their inception to February 11, 2023. These articles were screened, and data were extracted independently by two researchers. STATA 14.0 was used for statistical analysis of survival results. RESULTS: A total of 942 related articles were retrieved, 11 of which were included. Regarding lesion location, 57% (n = 552) originated in the sacral region, 41% (n = 398) in the skull base, and 2% (n = 19) in the spine (upper cervical). The local control (LC) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 96%, 93%, 83%, 76%, 71%, and 54%, respectively. The overall survival (OS) rates at 1, 2, 3, 5, 9, and 10 years in these studies were 99%, 100%, 93%, 85%, 76%, and 69%, respectively. Acute and late toxicities were acceptable, acute toxicities were mainly grade 1 to grade 2 and late toxicities were mainly grade 1 to grade 3. CONCLUSION: C-ion RT has attractive clinical application prospects and is an important local treatment strategy for chordomas. Encouraging results were observed in terms of LC and OS. Meanwhile, the acute and late toxicities were acceptable. PROSPERO registration number: CRD42023398792.

Carbon Ion Radiotherapy in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal cancer with limited treatment options and poor prognosis. Carbon ion radiotherapy (CIRT) has emerged as a promising treatment modality for HCC due to its unique physical and biological properties. CIRT uses carbon ions to target and destroy cancer cells with a high precision and efficacy. The Bragg Peak phenomenon allows precise dose delivery to the tumor while minimizing damage to healthy tissues. In addition, the high relative biological effectiveness of carbon ions can be shown against radioresistant and hypoxic tumor areas. CIRT also offers a shorter treatment schedule than conventional radiotherapy, which increases patient convenience and compliance. The clinical outcomes of CIRT for HCC have shown excellent local control rates with minimal side effects. Considering its physical and biological properties, CIRT may be a viable option for complex clinical scenarios such as patients with poor liver function, large tumors, re-irradiation cases, and tumors close to critical organs. Further research and larger studies are needed to establish definitive indications for CIRT and to compare its efficacy with that of other treatment modalities. Nevertheless, CIRT offers a potential breakthrough in HCC management, providing hope for improved therapeutic outcomes and reduced treatment-related toxicities.

Carbon-ion radiotherapy for oligometastatic liver disease: A national multicentric study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

Reports on the therapeutic efficacy and safety of carbon-ion radiotherapy (C-ion RT) for oligometastatic liver disease are limited, with insufficient evidence. This study aimed to evaluate the clinical outcomes of C-ion RT for oligometastatic liver disease at all Japanese facilities using the nationwide cohort data. We reviewed the medical records to obtain the nationwide cohort registry data on C-ion RT between May 2016 and June 2020. Patients (1) with oligometastatic liver disease as confirmed by histological or diagnostic imaging, (2) with ≤3 synchronous liver metastases at the time of treatment, (3) without active extrahepatic disease, and (4) who received C-ion RT for all metastatic regions with curative intent were included in this study. C-ion RT was performed with 58.0-76.0 Gy (relative biological effectiveness [RBE]) in 1-20 fractions. In total, 102 patients (121 tumors) were enrolled in this study. The median follow-up duration for all patients was 19.0 months. The median tumor size was 27 mm. The 1-year/2-year overall survival, local control, and progression-free survival rates were 85.1%/72.8%, 90.5%/78.0%, and 48.3%/27.1%, respectively. No patient developed grade 3 or higher acute or late toxicity. C-ion RT is a safe and effective treatment for oligometastatic liver disease and may be beneficial as a local treatment option in multidisciplinary treatment.

An international approach to estimating the indications and number of eligible patients for carbon ion radiation therapy (CIRT) in Australia.

BACKGROUND AND PURPOSE: To establish the treatment indications and potential patient numbers for carbon ion radiation therapy (CIRT) at the proposed national carbon ion (and proton) therapy facility in the Westmead precinct, New South Wales (NSW), Australia. METHODS: An expert panel was convened, including representatives of four operational and two proposed international carbon ion facilities, as well as NSW-based CIRT stakeholders. They met virtually to consider CIRT available evidence and experience. Information regarding Japanese CIRT was provided pre- and post- the virtual meeting. Published information for South Korea was included in discussions. RESULTS: There was jurisdictional variation in the tumours treated by CIRT due to differing incidences of some tumours, referral patterns, differences in decisions regarding which tumours to prioritise, CIRT resources available and funding arrangements. The greatest level of consensus was reached that CIRT in Australia can be justified currently for patients with adenoid cystic carcinomas and mucosal melanomas of the head and neck, hepatocellular cancer and liver metastases, base of skull meningiomas, chordomas and chondrosarcomas. Almost 1400 Australian patients annually meet the consensus-derived indications now. CONCLUSION: A conservative estimate is that 1% of cancer patients in Australia (or 2% of patients recommended for radiation therapy) may preferentially benefit from CIRT for initial therapy of radiation resistant tumours, or to boost persistently active disease after other therapies, or for re-irradiation of recurrent disease. On this basis, one national carbon ion facility with up to four treatment rooms is justified for Australian patients.

Clinical Outcomes of Intensity-modulated Carbon-ion Radiotherapy for Bone and Soft Tissue Tumors.

BACKGROUND/AIM: Carbon-ion radiotherapy (CIRT) for bone and soft tissue tumors (BSTs) has been reported to have favorable clinical outcomes. Intensity-modulated CIRT (IMCT) techniques have been developed to further reduce dose delivery to adjacent organs compared to conventional CIRT. We retrospectively analyzed the clinical results of IMCT for BSTs and investigated treatment efficacy and toxicity. PATIENTS AND METHODS: This study included 9 consecutive BSTs patients who underwent IMCT at the Kanagawa Cancer Center from January 2016 to April 2021. IMCT was administered at a dose of 60.8-70.4 Gy (relative biological effect) in 16 fractions. The time to event was calculated from the initiation of IMCT. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: The median age was 49 (range=16-71) years. The median observation period was 57.6 (range=7.0-77.8) months. There were 7 and 2 cases for IMCT because of proximity to the spinal cord and intestinal tract, respectively. There was one death during the observation period, which occurred 7.0 months after the initiation of treatment. Clinical recurrence occurred in 3 patients at 1.3, 17.8, and 22.4 months after the initiation of treatment, respectively. Acute toxicity of Grade 2 or higher was seen in 2 patients with Grade 2 pharyngeal mucositis. Late toxicities of Grade 2 or higher included 1 case each of Grade 2 neuralgia and peripheral neuropathy, as well as 1 case of Grade 3 fracture. CONCLUSION: IMCT for BSTs showed good local therapeutic efficacy and tolerable toxicity in patients with bone and soft tissue tumors.

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.

Immune checkpoint inhibitors and Carbon iON radiotherapy In solid Cancers with stable disease (ICONIC).

ICONIC is a multicenter, open-label, nonrandomized phase II clinical trial aiming to assess the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. The primary end point is objective response rate, and the secondary end points are safety, survival and disease control rate. Translational research is an exploratory aim. The planned sample size is 27 patients. The study combination will be considered worth investigating if at least four objective responses are observed. If the null hypothesis is rejected, ICONIC will be the first proof of concept of the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in oncology.

ICONIC is a multicenter, open-label, nonrandomized, phase II clinical trial aiming to evaluate the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. Considering that no clinical trials have been conducted thus far to assess the safety of the association between immune checkpoint inhibitors and carbon ion radiotherapy, the current clinical study will provide controlled data about the safety of this unprecedented therapeutic combination. Clinical Trial Registration: NCT05229614 (ClinicalTrials.gov).

Repeated Carbon-Ion Radiation Therapy for Intrahepatic Recurrent Hepatocellular Carcinoma.

PURPOSE: This retrospective study aimed to evaluate the safety and efficacy of repeated carbon-ion radiation therapy (CIRT) in patients with intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: We reviewed patients who underwent repeated CIRT for intrahepatic recurrent HCC between 2010 and 2020. RESULTS: Forty-one patients received multiple CIRT courses for HCC. During the second course, 17 (41.5%) and 24 (58.5%) of 41 patients underwent CIRT for local recurrence (LR) and intrahepatic recurrence after the first irradiation, respectively. The median age at the first course was 76 years, and the median tumor size in all the courses was 25 mm. Throughout all CIRT courses, the prescribed dose was 52.8 to 60.0 Gy (relative biological effectiveness), which was delivered in 4 to 12 fractions. The median follow-up period after the first and second CIRT was 40 and 21 months. Median overall survival (OS) after the first and second CIRT were 80 and 27 months, respectively. The 2- and 5-year OS after the first CIRT were 87.8% and 50.1%, and the 2-year OS rate after the second CIRT was 56.0%. The 1- and 2-year local control (LC) after the second CIRT was 93.4% and 83.0%, respectively. The median progression-free survival (PFS) after the second CIRT was 11 months. There were no significant differences in the LC and PFS between patients with LR and out-of-field recurrence (P = .83; 0.28, respectively). The albumin-bilirubin scores at 3 and 6 months after the second CIRT were not significantly different from those before irradiation. According to the Common Terminology Criteria for Adverse Events version 4.0, grade 4 or greater toxicities were not observed. CONCLUSIONS: Repeated CIRT for intrahepatic recurrent HCC was safe and effective, including reirradiation for LR. OS, LC, and PFS were satisfactory, and liver function was preserved. Repeated CIRT could be considered a treatment option for intrahepatic recurrent HCC.

Dose-volume constraints for head-and-neck cancer in carbon ion radiotherapy: A literature review.

BACKGROUND: Carbon ion radiotherapy (CIRT) has been applied in cancer treatment for over 25 years. However, guidelines for dose-volume constraints have not been established yet. The aim of this review is to summarize the dose-volume constraints in CIRT for head-and-neck (HN) cancer that were determined through previous clinical studies based on the Japanese models for relative biological effectiveness (RBE). METHODS: A literature review was conducted to identify all constraints determined for HN cancer CIRT that are based on the Japanese RBE models. RESULTS: Dose-volume constraints are reported for 17 organs at risk (OARs), including the brainstem, ocular structures, masticatory muscles, and skin. Various treatment planning strategies are also presented for reducing the dose delivered to OARs. CONCLUSIONS: The reported constraints will provide assistance during treatment planning to ensure that radiation to OARs is minimized, and thus adverse effects are reduced. Although the constraints are given based on the Japanese RBE models, applying the necessary conversion factors will potentially enable their application by institutions worldwide that use the local effect model for RBE.