Carbon-ion radiotherapy alone vs. standard dose photon radiation with carbon-ion radiotherapy boost for high-grade gliomas: a retrospective study.

BACKGROUND: This study aimed to compare the survival outcome and side effects in patients with primary high-grade glioma (HGG) who received carbon ion radiotherapy (CIRT) alone or as a boost strategy after photon radiation (photon + CIRTboost). PATIENTS AND METHODS: Thirty-four (34) patients with histologically confirmed HGG and received CIRT alone or Photon + CIRTboost, with concurrent temozolomide between 2020.03-2023.08 in Wuwei Cancer Hospital & Institute, China were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and acute and late toxicities were analyzed and compared. RESULTS: Eight WHO grade 3 and 26 grade 4 patients were included in the analysis. The median PFS in the CIRT alone and Photon + CIRTboost groups were 15 and 19 months respectively for all HGG cases, and 15 and 17.5 months respectively for grade 4 cases. The median OS in the CIRT alone and Photon + CIRTboost groups were 28 and 31 months respectively for all HGG cases, and 21 and 19 months respectively for grade 4 cases. No significant difference in these survival outcomes was observed between the CIRT alone and Photon + CIRTboost groups. Only grade 1 acute toxicities were observed in CIRT alone and Photon + CIRTboost groups. CIRT alone group had a significantly lower ratio of acute toxicities compared to Photon + CIRTboost (3/18 vs. 9/16, p = 0.03). No significant difference in late toxicities was observed. CONCLUSION: Both CIRT alone and Photon + CIRTboost with concurrent temozolomide are safe, without significant differences in PFS and OS in HGG patients. It is meaningful to explore whether dose escalation of CIRTboost might improve survival outcomes of HGG patients in future randomized trials.

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.

Hypofractionated proton and carbon ion beam radiotherapy for sacrococcygeal chordoma (ISAC): An open label, randomized, stratified, phase II trial.

INTRODUCTION: Sacrococcygeal chordomas have high recurrence rates and are challenging to treat. METHODS: In this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3-5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). RESULTS: The study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5-6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). CONCLUSION: The initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma.

Long-term outcomes after particle radiation therapy in patients with nasopharyngeal adenoid cystic carcinoma.

BACKGROUND: Nasopharyngeal adenoid cystic carcinoma (NACC) is a relatively rare salivary gland tumor that is generally associated with poor outcomes. High-dose radiotherapy is a key treatment for patients with NACC. This study reported the long-term efficacy and safety of particle beam radiation therapy (PBRT) for NACC. METHODS AND MATERIALS: Twenty-six patients with nonmetastatic NACC who received definitive PBRT alone were included in this retrospective study. The majority of patients (92.3%) had locally advanced disease. Twenty-five (96.15%) patients received intensity-modulated proton radiotherapy (IMPT) followed by a carbon ion radiotherapy (CIRT) boost, and one patient received CIRT alone. Overall survival (OS), local control (LC), regional control (RC), and distant metastasis control (DMC) rates were calculated via the Kaplan-Meier method. RESULTS: The median follow-up time was 46.95 months for the entire cohort. Seven patients experienced local recurrence, and one patient experience neck lymph node recurrence. The 3- and 4-year OS, LC, RC, and DMC rates were 100% and 91.7%, 92.3% and 84.6%, 95.8% and 87.8%, and 90.2% and 71.3%, respectively. A total of 91.3% of the patients achieved complete remission of gross tumors at 1 year after PBRT. Severe acute toxicity was observed in only two patients. A grade 4 decrease in visual acuity was observed in one patient with orbital apex invasion. No late grade 3 or 5 toxicity was observed. CONCLUSION: Definitive PBRT provided a satisfactory 4-year OS for patients with locally advanced NACC. The toxicity was acceptable and mild. Further follow-up is necessary to confirm the efficacy and safety of definitive PBRT for patients with NACC.

Effects of Photon versus Carbon-Ion Irradiation in the Rat Cervical Spinal Cord - a Serial T2 and Diffusion-weighted Magnetic Resonance Imaging Study.

Carbon-ion irradiation is increasingly used at the skull base and spine near the radiation-sensitive spinal cord. To better characterize the in vivo radiation response of the cervical spinal cord, radiogenic changes in the high-dose area were measured in rats using magnetic resonance imaging (MRI) diffusion measurements in comparison to conventional photon irradiations. In this longitudinal MRI study, we examined the gray matter (GM) of the cervical spinal cord in 16 female Sprague-Dawley rats after high-dose photon (n = 8) or carbon-ion (12C) irradiation (n = 8) and in 6 sham-exposed rats until myelopathy occurred. The differences in the diffusion pattern of the GM of the cervical spinal cord were examined until the endpoint of the study, occurrence of paresis grade II of both forelimbs was reached. In both radiation techniques, the same order of the occurrence of MR-morphological pathologies was observed - from edema formation to a blood spinal cord barrier (BSCB) disruption to paresis grade II of both forelimbs. However, carbon-ion irradiation showed a significant increase of the mean apparent diffusion coefficient (ADC; P = 0.031) with development of a BSCB disruption in the GM. Animals with paresis grade II as a late radiation response had a highly significant increase in mean ADC (P = 0.0001) after carbon-ion irradiation. At this time, a tendency was observed for higher mean ADC values in the GM after 12C irradiation as compared to photon irradiation (P = 0.059). These findings demonstrated that carbon-ion irradiation leads to greater structural damage to the GM of the rat cervical spinal cord than photon irradiation due to its higher linear energy transfer (LET) value.

Assessing the Impact of Charged Particle Radiation Therapy for Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.

Effectiveness and Safety of Carbon Ion Radiotherapy in Solid Tumors: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the effectiveness of carbon ion radiotherapy (CIRT) compared to that of conventional radiotherapy in patients with various types of solid tumors. MATERIALS AND METHODS: We systematically searched eight electronic databases from inception until August 2022 in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The comparative effectiveness of the different treatment options was assessed by a random-effects meta-analysis. RESULTS: This review included 34 comparative studies and three treatment groups. Overall, the meta-analysis indicated comparable local control rates between the CIRT and control groups [pooled risk ratio (RR)=1.02, 95% confidence interval (CI) 0.90-1.15]. The local control rate in the CIRT group was higher than that in the photon therapy group, but slightly lower than that in the proton radiation therpy (PRT) group. Additionally, the CIRT group had significantly higher overall survival (OS) (RR=1.19, 95% CI=1.01-1.42) and progression-free survival (PFS) (RR=1.50, 95% CI=1.01-2.21) rates compared to the control group. In the subgroup analysis, survival rates were similar between the CIRT and PRT groups. CONCLUSION: CIRT was associated with improved toxicity, local tumor control, OS, and PFS compared to conventional treatments. Therefore, CIRT was found to be a safe and effective option for achieving local control in patients with solid tumors.

Survival outcomes and toxicity profiles among patients with nonmetastatic nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy: A propensity score-matched analysis.

OBJECTIVES: To compare survival outcomes and toxic effects among patients with newly diagnosed nonmetastatic nasopharyngeal carcinoma (NPC) when treated with intensity-modulated radiotherapy (IMRT) versus IMRT + carbon-ion radiotherapy (CIRT). METHODS: We performed a retrospective propensity score matching analysis (1:1) of patients treated with IMRT and IMRT + CIRT. Descriptive statistics were used to examine the baseline characteristics of the patients. Survival was estimated using the Kaplan-Meier method. Univariate and multivariable logistic regression analysis were used to identify the independent predictors of survival. We examined the association between risk factors and adverse events (AEs) using chi-square tests. Cox model and logistic regression were used to analyze AEs. RESULTS: Hundred and nine patients who received IMRT + CIRT were included and the median follow-up time was 20.6 months (range: 4.6-82 months). There were no statistically significant differences in locoregional failure-free survival, distant metastasis-free survival, disease-free survival, or overall survival between the two groups, but potentially better in IMRT + CIRT group (p > 0.05, respectively). Nodal boost was the only significant factor associated with LRFS and DFS on multivariable analysis. Thirty-seven patients (34.0%) developed grade 3 acute OMs and no grade 4 acute OMs were observed in IMRT + CIRT group. All patients in IMRT + CIRT group developed grade 1 dermatitis; while in the match group, 76 patients developed grade 1 dermatitis, 27 patients developed grade 2 dermatitis, 5 patients developed grade 3 dermatitis, 1 patient developed grade 4 dermatitis. IMRT + CIRT treatment was associated with a significant trend of lower grades of OM and dermatitis (p < 0.05, respectively). Any severe (i.e., grade 3) chronic AEs, such as xerostomia, skin fibrosis, temporal lobe necrosis, osteoradionecrosis, or radiation-induced optic neuropathy, was not observed. CONCLUSIONS: In this study, IMRT + CIRT was associated with significantly reduced acute toxicity burden compared with full course of IMRT, with excellent survival outcomes. Patients with persistent disease after treatment and treated with nodal boost had a worse outcome. More accurate assessments of IMRT + CIRT to primary nonmetastatic NPC patients will be imperative.

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.

Kaplan lecture 2023: lymphopenia in particle therapy.

PURPOSE: Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberrations in blood cells irradiated ex-vivo. The explanation was based on the volume effect, i.e. the sparing of larger volumes of normal tissue in Bragg peak therapy. Here we will review the current knowledge about the difference in lymphopenia between particle and photon therapy and the consequences. CONCLUSIONS: There is nowadays an overwhelming evidence that particle therapy reduces significantly the radiotherapy-induced lymphopenia in several tumor sites. Because lymphopenia turns down the immune response to checkpoint inhibitors, it can be predicted that particle therapy may be the ideal partner for combined radiation and immunotherapy treatment and should be selected for patients where severe lymphopenia is expected after X-rays.

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.

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.

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.

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.

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.

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.

Combined Photon and Carbon Ion Radiation Therapy for Sinonasal Malignancies: Results of the HIT-SNT Prospective Phase 2 Trial.

PURPOSE: Radiation treatment of sinonasal malignancies is a challenging task due to proximity to critical structures of the head and neck and skull base. Local tumor control is highly dose-dependent, but dose application is limited due to accompanying toxicity and dose constraints. To evaluate the toxicity and efficacy of combined radiation treatment with intensity-modulated radiation therapy (IMRT) and carbon ion boost, we conducted a prospective phase 2 IMRT-Heidelberg Ion-Beam Therapy Sinonasal Tumors (HIT-SNT) trial. METHODS AND MATERIALS: Between 2011 and 2019, we treated 35 patients with histologically proven, incompletely resected or inoperable adeno- (51%) or squamous cell carcinoma (49%) of the paranasal sinuses with combined IMRT (50 Gy) and carbon ion boost (24 Gy relative biologic effectiveness) to a total dose of 74 Gy. RESULTS: Acute mucositis Common Terminology Criteria for Adverse Events (CTCAE) grade 3 occurred in 12% of patients (n = 4) and was accompanied by odynophagia CTCAE grade 3. Except for 1 case of grade 3 weight loss, no other acute high-grade toxicity (grade 3-4) was observed. In a small patient cohort of 15 patients eligible for long-term follow-up we have seen no high-grade (grade ≥3) long-term side effects 2 years after radiation therapy. None of these patients suffered from therapy-associated vision or hearing loss. Secondary endpoints were 2-year overall survival, 2-year local progression-free survival, 2-year progression-free survival, and 2-year metastases-free survival with 79.4%, 61.8%, 61.8%, and 64.8%, respectively. CONCLUSIONS: To our knowledge, this is the first prospective data on toxicity and outcome of bimodal radiation therapy for the rare entity of sinonasal malignancies. Our study shows a low rate of CTCAE-reported acute toxicity with reasonable tumor control and survival rates after bimodal radiation therapy, which therefore remains a therapy approach to be further evaluated.

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.