Carbon-Ion Radiotherapy Combined with Concurrent Chemotherapy for Locally Advanced Pancreatic Cancer: A Retrospective Case Series Analysis.

Systemic chemotherapy has significantly improved in recent years. In this study. the clinical impact of carbon-ion radiotherapy (CIRT) with concurrent chemotherapy for locally advanced unresectable pancreatic cancer (URPC) was evaluated. METHODS: Patients with URPC who were treated with CIRT between January 2016 and December 2020 were prospectively registered and analyzed. The major criteria for registration were (1) diagnosed as URPC on imaging; (2) pathologically diagnosed adenocarcinoma; (3) no distant metastasis; (4) Eastern Cooperative Oncology Group performance status of 0-2; (5) tumors without gastrointestinal tract invasion; and (6) available for concurrent chemotherapy. Patients who received neoadjuvant chemotherapy (NAC) for more than one year prior to CIRT were excluded. RESULTS: Forty-four patients met the inclusion criteria, and thirty-seven received NAC before CIRT. The median follow-up period of living patients was 26.0 (6.0-68.6) months after CIRT. The estimated two-year overall survival, local control, and progression-free survival rates after CIRT were 56.6%, 76.1%, and 29.0%, respectively. The median survival time of all patients was 29.6 months after CIRT and 34.5 months after the initial NAC. CONCLUSION: CIRT showed survival benefits for URPC even in the multiagent chemotherapy era.

Safety and Efficacy of Re-irradiation With Carbon-ion Radiotherapy for Pelvic Recurrence of Rectal Cancer After Preoperative Chemoradiotherapy: A Retrospective Analysis.

BACKGROUND/AIM: Previous evaluation of the safety and clinical efficacy of re-irradiation for pelvic recurrence of rectal cancer after preoperative chemoradiotherapy (PCRT) and rectal surgery is insufficient. We evaluated the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for pelvic recurrence of rectal cancer after PCRT. PATIENTS AND METHODS: We reviewed the medical records of patients treated with C-ion RT between August 2011 and December 2021 and analyzed the data of seven consecutive patients. The probabilities of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Toxicities were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: The median follow-up duration after C-ion RT initiation was 30.9 months. Five patients received 73.6 Gy [relative biological effectiveness (RBE)] in 16 fractions, and two patients received 57.6 Gy (RBE) in 12 fractions. All patients completed C-ion RT as scheduled. Two-year estimated OS, LC, and PFS rates after C-ion RT initiation were 100%, 83.3%, and 28.6%, respectively. No patients developed grade ≥3 acute toxicity. Regarding late toxicities, one patient who received Gore-Tex sheets as a spacer before C-ion RT developed grade 3 colon perforation, and then developed a grade 3 urinary tract disorder. One patient developed grade 2 peripheral neuropathy. CONCLUSION: C-Ion RT showed favorable local efficacy with minimal toxicity. C-Ion RT might be an effective treatment option for pelvic recurrence of rectal cancer after PCRT even when re-irradiation of the pelvis is required.

Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy.

BACKGROUND: The efficacy of first-line chemoradiotherapy for overall survival (OS) might be confounded by the subsequent treatments in patients with locally advanced non-small cell lung cancer (NSCLC). In this study, we assessed the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after chemoradiotherapy for locally advanced NSCLC using patient-level data. PATIENTS AND METHODS: Between January 2011 and December 2018, 45 patients with locally advanced NSCLC who had received first-line chemoradiotherapy and in whom recurrence occurred were analysed. The associations of PFS and PPS with OS were analysed at the individual level. RESULTS: Linear regression and Spearman rank correlation analyses revealed that PPS was strongly correlated with OS (r = 0.72, p < 0.05, R2 = 0.54), whereas PFS was moderately correlated with OS (r = 0.58, p < 0.05, R2 = 0.34). The Glasgow prognostic score and liver metastases at recurrence were significantly associated with PPS (p < 0.001). CONCLUSIONS: The current analysis of individual-level data of patients treated with first-line chemoradiotherapy implied that PPS had a higher impact on OS than PFS in patients with locally advanced NSCLC. Additionally, current perceptions indicate that treatment beyond progression after first-line chemoradiotherapy might strongly affect OS.

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture.

The promising results of the PACIFIC study led to the approval of consolidation durvalumab for coverage by the National Health Insurance (NHI) in 2018 for patients with locally-advanced unresectable non-small cell lung carcinoma (NSCLC) treated with definitive concurrent chemoradiotherapy (CCRT). However, the effect of NHI coverage on the patterns of care for this population remains unclear. Here, we conducted a questionnaire-based survey to determine the patterns of care for patients with stage II-III NSCLC treated with definitive radiotherapy in 2017 (pre-durvalumab era) or in 2019 (post-durvalumab era). Data were obtained from 11 radiotherapy facilities in Gunma prefecture, which has a population of 1.94 million. We identified 80 and 83 patients with stage II-III NSCLC who received definitive radiotherapy in Gunma in 2017 and 2019, respectively. At a given facility, CCRT was the treatment of choice in a significantly greater proportion of patients in 2019 than in 2017 (66% ± 20% vs 51% ± 29%, P = 0.041). Intensity-modulated radiotherapy (IMRT) was more frequent in 2019 than in 2017 (24% vs 1.2%). Carboplatin plus paclitaxel was used for CCRT at higher rate in 2019 than in 2017 (73% vs 44%). Consolidation durvalumab was performed in 73% (40/55) of CCRT-treated patients in 2019, and the treatment was performed for the planned 12 months in 45% (18/40) of patients. These data indicate that NHI coverage of durvalumab might be a possible reason for choosing CCRT in patients with stage II-III NSCLC in the real-world setting.

Post-Progression Survival Is Strongly Associated with Overall Survival in Patients Exhibiting Postoperative Relapse of Non-Small-Cell Lung Cancer Harboring Sensitizing EGFR Mutations.

Background and Objective: Patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations show a good response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). The subsequent treatments influence the evaluability of the efficacy of front-line therapy on overall survival (OS). Consequently, we evaluated the associations of relapse-free survival (RFS) and post-progression survival (PPS) with OS in patients who exhibited postoperative relapse of EGFR-mutated NSCLC. Materials and Methods: We analyzed the data of 35 patients with EGFR-mutated NSCLC who underwent complete resection between January 2007 and June 2019. The correlations of RFS and PPS with OS were evaluated at the individual patient level. Results: Linear regression and Spearman's rank correlation analyses demonstrated that the PPS highly correlated with OS (r = 0.91, p < 0.05, R2 = 0.85), whereas the RFS weakly associated with OS (r = 0.36, p < 0.05, R2 = 0.25). Age and performance status at relapse were significantly associated with PPS. Conclusion: Overall, PPS was more strongly and significantly associated with OS than RFS. These results suggest that the OS of our cohort may be affected by treatments, besides postoperative relapse. However, larger-scale prospective studies are needed to confirm these results.

Stereotactic body radiotherapy for adenoid cystic carcinoma metastatic to the lung: a case report.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare malignant tumor involving mostly the head and neck region, and frequently the salivary glands. The development of lung metastasis after treatment of the primary tumor is a common occurrence in ACC. Although lung metastases show a slow rate of growth, approximately 10% of patients die from distant metastases. The radioresistance of ACC limits the efficacy of conventional radiotherapy for lung metastases, and the optimal dose remains to be determined. Stereotactic body radiotherapy (SBRT) using CyberKnife can deliver a high dose to the lung tumor, while sparing the surrounding normal lung tissues, leading to favorable local control in non-squamous cell lung cancer and metastatic lung tumors. We report a case of lung metastases from ACC treated successfully with SBRT using CyberKnife. CASE PRESENTATION: A 76-year-old Japanese man with ACC who was treated with carbon ion radiotherapy for a primary oropharynx tumor presented with three metastatic lesions in the lung. The tumor masses were located in the right upper, right lower, and left lower lobes of the lungs. Surgical resection was not indicated because of the presence of multiple tumors. The patient underwent SBRT at 60 Gy in 10 sequential fractions for each tumor. The biologically effective dose based on an alpha/beta ratio of 2 Gy was 240 Gy per tumor. The percentage of the total lung volume irradiated with >20 Gy was 4.9%, 3.2%, and 2.6% for each tumor. The patient developed acute radiation pneumonitis during the initial therapy, which resolved at 6 months after the CyberKnife treatment. At 21 months after the first CyberKnife treatment, three tumors showed no signs of recurrence. No late toxicity was observed. CONCLUSIONS: SBRT using CyberKnife is an effective and feasible approach to the management of multiple lung metastases of ACC.

Induction of Micronuclei in Cervical Cancer Treated with Radiotherapy.

Micronuclei (MN) trigger antitumor immune responses via the cyclic GMP-AMP synthase-signaling effector stimulator of interferon genes (cGAS-STING) pathway. Radiotherapy induces MN in peripheral blood lymphocytes. However, data for solid tumors are lacking. Here, we analyzed MN post-radiotherapy in solid tumor samples. Tumor biopsy specimens were obtained from seven prospectively recruited patients with cervical cancer, before treatment and after receiving radiotherapy at a dose of 10 Gy (in five fractions). The samples were stained with 4',6-diamidino-2-phenylindole dihydrochloride, and 200 nuclei per sample were randomly identified and assessed for the presence of MN or apoptosis, based on nuclear morphology. The median number of MN-harboring nuclei was significantly greater in samples from patients treated with radiotherapy than in pre-treatment samples (151 (range, 16-327) versus 28 (range, 0-61); p = 0.015). No significant differences in the number of apoptotic nuclei were observed between pre-treatment and 10 Gy samples (5 (range, 0-30) versus 12 (range, 2-30); p = 0.30). This is the first report to demonstrate MN induction by radiotherapy in solid tumors. The results provide clinical evidence of the activation of antitumor immune responses by radiotherapy.

Relative Biological Effectiveness of Carbon Ions for Head-and-Neck Squamous Cell Carcinomas According to Human Papillomavirus Status.

Carbon-ion radiotherapy (CIRT) has strong antitumor effects and excellent dose conformity. In head-and-neck squamous cell carcinoma (HNSCC), human papillomavirus (HPV) status is a prognostic factor for photon radiotherapy outcomes. However, the effect of HPV status on the sensitivity of HNSCCs to carbon ions remains unclear. Here, we showed that the relative biological effectiveness (RBE) of carbon ions over X-rays was higher in HPV-negative cells than in HSGc-C5 cells, which are used for CIRT dose establishment, whereas the RBE in HPV-positive cells was modest. These data indicate that CIRT is more advantageous in HPV-negative than in HPV-positive HNSCCs.

Efficacy and Feasibility of Salvage Re-Irradiation with CyberKnife for In-Field Neck Lymph Node Recurrence: A Retrospective Study.

Neck lymph node (LN) recurrence in the irradiated field represents an important aspect of treatment failure after primary radiotherapy owing to the lack of a standard treatment. The aim of this study is to investigate the efficacy and safety of CyberKnife treatment for neck LN recurrence after radiotherapy. Between 2008 and 2016, 55 neck LN recurrences after radiotherapy in 16 patients were treated with CyberKnife. The median follow-up period was 17 months (range, 2-53 months). The median previous radiotherapy dose was 68 Gy (range, 50-70 Gy). The median marginal dose as equivalent dose delivered in 2-Gy fractions (α/ß = 10) was 50 Gy (range, 40-58 Gy). The one-year local control (LC) and overall survival rates were 81% and 71%, respectively. The one-year LC was higher with a target volume ≤1.0 cm3 than that with a target volume >1.0 cm3 (p = 0.006). Fatal bleeding was observed in one patient who had large (91 cm3) and widespread tumor with invasion to the carotid artery before CyberKnife treatment. CyberKnife treatment for neck LN recurrence is safe and feasible in most cases. Indication for the treatment should be carefully considered for large and widespread tumors.

Impact of CT-based brachytherapy in elderly patients with cervical cancer.

PURPOSE: Three-dimensional image-guided brachytherapy (3D-IGBT) has become the standard therapy for patients with cervical cancer. However, in this population, the impact of 3D-IGBT in elderly individuals remains unknown. This study assessed the efficacy of 3D-IGBT for elderly patients with cervical cancer. METHODS AND MATERIALS: We performed a retrospective chart review of 105 consecutive patients with cervical squamous cell carcinoma aged ≥70 years who received radiotherapy alone between January 2001 and September 2014. All patients were treated with external beam radiotherapy and high-dose-rate intracavitary brachytherapy. We assessed the treatment outcomes in all patients. We then compared outcomes between two groups: patients treated by changing the Point A dose at brachytherapy (Group A, n = 71) and those treated with 3D-IGBT at least twice (Group B, n = 34). RESULTS: The median followup period was 59 (range, 6-203) months; the median age was 77 years. The 5-year local control and cause-specific survival rates were 89% and 78%, respectively. The 5-year cumulative rates of late toxicities of the rectum and bladder of Grade ≥3 were 2.0% and 4.2%, respectively. No statistically significant differences were observed in the local control and cause-specific survival rates, or in the incidence of rectal toxicities between groups. The 3-year cumulative rates of urinary toxicity of Grade ≥1 were 20.4% and 6.9% in Group A and Group B, respectively (p = 0.035). CONCLUSION: In elderly patients with cervical cancer, 3D-IGBT could be performed safely and effectively and contributed to decreasing urinary toxicity incidence rates.

Dosimetric parameters predictive of nasolacrimal duct obstruction after carbon-ion radiotherapy for head and neck carcinoma.

BACKGROUND AND PURPOSE: Little information is available on the risk factors for nasolacrimal duct obstruction after radiotherapy for head and neck tumors. We investigated the incidence and predictive dosimetric parameters for nasolacrimal duct obstruction following carbon-ion radiotherapy for head and neck tumors. MATERIALS AND METHODS: Twenty-eight patients with head and neck non-squamous cell carcinoma were analyzed in this single-institution prospective study. More than half of the tumors were located in the nasal cavity and maxillary sinus. Carbon-ion radiotherapy consisting of 57.6 or 64.0 Gy(relative biological effectiveness; RBE) in 16 fractions was administered. Nasolacrimal duct obstruction was recorded according to Common Terminology Criteria for Adverse Events version 4.0. Cutoff values were determined using receiver operating characteristic (ROC) curve analysis. VX indicates the volume irradiated with X Gy(RBE). RESULTS: The median follow-up period was 60.3 months. Incidences of Grade 1 and 2 nasolacrimal duct obstructions were 46% (13/28) and 7% (2/28), respectively; no Grade 3 or greater toxicities were recorded. Throughout the dose range, the volumes of the irradiated nasolacrimal ducts were significantly higher in the obstruction-positive patients than in the obstruction-negative patients (p < 0.001 for V10, V20, V30, V40, V50, and V60). Cutoff values determined by the ROC curve analysis classified the obstruction-positive patients with an accuracy of >96% over the entire range of V10-V60. CONCLUSION: The incidence and predictive dosimetric parameters for nasolacrimal duct obstruction after carbon-ion radiotherapy were demonstrated in a prospective cohort. These data should help optimize carbon-ion radiotherapy treatments for patients with head and neck tumors.

Radiosensitivity Differences between EGFR Mutant and Wild-Type Lung Cancer Cells are Larger at Lower Doses.

In the era of precision medicine, radiotherapy strategies should be determined based on genetic profiles that predict tumor radiosensitivity. Accordingly, pre-clinical research aimed at discovering clinically applicable genetic profiles is needed. However, how a given genetic profile affects cancer cell radiosensitivity is unclear. To address this issue, we performed a pilot in vitro study by utilizing EGFR mutational status as a model for genetic profile. Clonogenic assays of EGFR mutant (n = 6) and wild-type (n = 9) non-small cell lung carcinoma (NSCLC) cell lines were performed independently by two oncologists. Clonogenic survival parameters SF2, SF4, SF6, SF8, mean inactivation dose (MID), D10, D50, α, and ß were obtained using the linear quadratic model. The differences in the clonogenic survival parameters between the EGFR mutant and wild-type cell lines were assessed using the Mann-Whitney U test. As a result, for both datasets, the p values for SF2, SF4, D50, α, and α/ß were below 0.05, and those for SF2 were lowest. These data indicate that a genetic profile of NSCLC cell lines might be predictive for their radiation response; i.e., EGFR mutant cell lines might be more sensitive to low dose- and low fraction sized-irradiation.

Carbon-ion radiotherapy for inoperable endometrial carcinoma.

This is a pooled analysis to evaluate the toxicity and efficacy of carbon-ion radiotherapy (C-ion RT) for inoperable endometrial carcinoma. Eligible patients had previously untreated Stage I-III endometrial carcinoma without para-aortic lymph node metastasis. Total dose to the tumor was 62.4-74.4 Gy [relative biological effectiveness (RBE)] in 20 fractions, and the dose to the gastrointestinal tract was limited to <60 Gy (RBE). Intracavitary brachytherapy was not combined in the present study. Fourteen patients with endometrial carcinoma were analyzed. Ten of the 14 patients were judged medically inoperable, and the others refused surgery. The numbers of patients with Stage I, II and III disease were 1, 9 and 4, respectively. Tumor size was 3.8-13.8 cm in maximum diameter. Median follow-up periods for all patients and surviving patients were 50 months (range, 12-218 months) and 78 months (range, 23-218 months), respectively. Two of three patients receiving 62.4-64.8 Gy (RBE) had local recurrence whereas none of 11 patients receiving 68.0 Gy (RBE) or more had local recurrence. Three patients developed distant metastases and one of them also had local recurrence. The 5-year local control, progression-free survival, overall survival, and cause-specific survival rates were 86%, 64%, 68% and 73%, respectively. No patient developed Grade 3 or higher acute or late toxicity. The present study showed that C-ion RT alone could be a safe and curative treatment modality for inoperable endometrial carcinoma.

Human papillomavirus genotype affects metastatic rate following radiotherapy in patients with uterine cervical cancer.

Human papillomavirus (HPV) infection is well known as a major etiological risk factor associated with carcinogenesis in uterine cervical cancer. However, few reports have investigated the association between HPV genotype and outcome in patients with uterine cervical cancer following radiotherapy (RT). The aim of the present study was to investigate the association between the HPV genotype and clinical outcome following RT in Japanese patients with uterine cervical cancer. Between November 2001 and August 2006, 157 Japanese women with uterine cervical cancer were treated with RT or concurrent chemoradiotherapy with curative intent. Pretreatment, formalin-fixed, paraffin-embedded biopsies were obtained from 83 patients. HPV genotypes were determined using the polymerase chain reaction method. Patients were categorized, according to HPV L1 protein sequence homology, into the HPV α-9 (HPV 16, 31, 33, 52, and 58), HPV α-7 (HPV 18, 39, 45, 59, and 68) or 'other' (HPV 51 and 56) groups. Associations between HPV genotype and clinical outcome following RT were evaluated. A total of 54 (65.1%) tumors were HPV α-9-positive, 13 (15.7%) were HPV α-7-positive, 2 (2.4%) were categorized under 'other' and 14 (16.9%) were HPV-negative. There were no significant differences in age, FIGO stage, regional lymph node metastases rate at diagnosis, or concurrent chemotherapy administration between the HPV α-9 and α-7 groups. The median follow-up period was 52 months (range, 2-156 months). The 5-year disease-free survival rates were 54.5 and 30.8% in the HPV α-9 and α-7 groups, respectively (P=0.034), and the 5-year distant metastasis rates were 38.0 and 69.2%, respectively (P=0.015). There were no significant differences in the 5-year local control or overall survival (OS) rates between the two groups. HPV genotype affected the 5-year distant metastatic rate, however not the 5-year local control or OS rate in patients with uterine cervical cancer following RT.

Clinical outcomes of carbon ion radiotherapy with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma in a phase 1/2 clinical trial (Protocol 1001).

We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010 and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to determine the maximum tolerated dose of C-ion RT. In the phase 2 component, the efficacy and safety of C-ion RT with concurrent chemotherapy were evaluated using the dose determined in the phase 1 component. The median follow-up duration was 30 months. Two patients did not receive chemotherapy because of anemia or leukocytopenia immediately prior to commencing treatment; 31 patients were analyzed. None of the patients developed dose-limiting toxicities. The recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2 component, two patients developed Grade 3-4 toxicities in the gastrointestinal tract, due to repeated laser coagulation or peritonitis caused by appendicitis. In the patients treated with the RD, the 2-year local control, progression-free survival, and overall survival rates were 71%, 56%, and 88%, respectively. C-ion RT with concurrent weekly cisplatin was well tolerated in patients with locally advanced uterine cervical adenocarcinoma. Our findings support further investigations into the efficacy of this strategy.

Long-term Outcomes of Carbon-ion Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix.

BACKGROUND/AIM: To evaluate the long-term outcomes of carbon-ion radiotherapy (C-ion RT) for locally advanced cervical squamous cell carcinoma (LAC-SqCC) in 2 prospective phase I/II studies. PATIENTS AND METHODS: In the first study, 14 patients were treated with 68.8-72.8 Gy (RBE)/24 fractions. In a subsequent study, 22 patients were treated with 64.0-72.0 Gy (RBE)/20 fractions while limiting the dose to the gastro-intestinal (GI) <60 Gy (RBE). RESULTS: The 10-year local control rates were 92% and 61% for the patients administered a total dose of 72.0-72.8 Gy (RBE) and 64.0-68.8 Gy (RBE), respectively. Two patients in the first study developed grade 3/4 rectal or bladder complications; however, no grade 3 or higher complications occurred in the second study. CONCLUSION: C-ion RT with a higher dose was associated with excellent LC in LAC-SqCC. Long-term safety was confirmed based on the establishment of dose constraints for the GI tract.

One-step Protocol for Evaluation of the Mode of Radiation-induced Clonogenic Cell Death by Fluorescence Microscopy.

Research on ionizing radiation (IR)-induced clonogenic cell death is important for understanding the effect of IR on malignant tumors and normal tissues. Here, we describe a quick and cost-effective one-step assay for simultaneously assessing the major modes of clonogenic cell death induced by IR, i.e., apoptosis, mitotic catastrophe, and cellular senescence. In this method, cells grown on a cover slip are irradiated with X-rays and stained with 4',6-diamidino-2-phenylindole dihydrochloride (DAPI). Using fluorescence microscopy, apoptosis, mitotic catastrophe, and cellular senescence are identified based on the characteristic morphologies of the DAPI-stained nuclei. Apoptosis is determined by the presence of apoptotic bodies (i.e., condensed and fragmented nuclei). Mitotic catastrophe is determined by the presence of nuclei that exhibit two or more distinct lobes and micronuclei. Cellular senescence is determined by the presence of senescence-associated heterochromatic foci (i.e., nuclear DNA containing 30-50 bright, dense foci). This approach allows the experimenter to easily screen for clonogenic cell death modes using various cell lines, treatment settings, and/or time points, with the goal of elucidating the mechanisms of cell death in the target cells and conditions of interest.

Clinical Impact of Re-irradiation with Carbon-ion Radiotherapy for Lymph Node Recurrence of Gynecological Cancers.

BACKGROUND/AIM: To evaluate the safety and efficacy of re-irradiation with carbon-ion radiotherapy (C-ion RT) for lymph node recurrence of gynecological cancers after definitive radiotherapy. PATIENTS AND METHODS: Data regarding patients with unresectable and isolated recurrent lymph node from gynecological cancer after definitive radiotherapy were analyzed. Total dose of C-ion RT was 48-57.6 Gy (RBE) in 12 or 16 fractions. RESULTS: Sixteen patients received re-irradiation by C-ion RT were analyzed. Median follow-up was 37 months. Median tumor size was 27 mm. None developed Grade 1 or higher acute toxicities and Grade 3 or higher late toxicities. The 3-year overall survival, local control and disease-free survival rates after C-ion RT were 74%, 94% and 55%, respectively. CONCLUSION: Re-irradiation with C-ion RT for lymph node recurrence of gynecological cancers after definitive radiotherapy can be safe and effective. This result suggested that C-ion RT could be a curative treatment option for conventionally difficult-to-cure patients.

Dose-volume histogram analysis of brainstem necrosis in head and neck tumors treated using carbon-ion radiotherapy.

BACKGROUND AND PURPOSE: We aimed to evaluate the relationship between brainstem necrosis and dose-volume histograms in patients with head and neck tumors after carbon-ion radiotherapy. MATERIAL AND METHODS: We evaluated 85 patients with head and neck tumors who underwent carbon-ion radiotherapy and were followed-up for ≥12months. Brainstem necrosis was evaluated using the Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: The median follow-up was 24months, and four patients developed grade 1 brainstem necrosis, with 2-year and 3-year cumulative rates of 2.8% and 6.5%, respectively. Receiver operating characteristic curve analysis revealed the following significant cut-off values: a maximum brainstem dose of 48Gy (relative biological effectiveness [RBE]), D1cm3 of 27Gy (RBE), V40Gy (RBE) of 0.1cm3, V30Gy (RBE) of 0.7cm3, and V20Gy (RBE) of 1.4cm3. Multivariate analysis revealed that V30Gy (RBE) was most significantly associated with brainstem necrosis. The 2-year cumulative rates were 33% and 0% for V30Gy (RBE) of ≥0.7cm3 and <0.7cm3, respectively (p<0.001). CONCLUSIONS: The present study indicated that the dose constraints might help minimize brainstem necrosis after carbon-ion radiotherapy.

Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.

To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.