Safety Of Carbon-ion Radiotherapy Research Articles

Carbon-Ion Radiotherapy for Postoperative Locoregional Recurrence of Pancreatic Cancer

To evaluate the efficacy and safety of carbon-ion radiotherapy (CIRT) for patients with locoregional recurrence after surgery for pancreatic cancer. A total of 32 patients, who underwent CIRT for locoregional recurrence after surgery for pancreatic cancer between January 2015 and July 2022, were retrospectively analyzed. The total dose of CIRT was 55.2 Gy (RBE) in 12 fractions. Concurrent chemotherapy included gemcitabine for 17 patients and S-1 for 3 patients. The overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated. The median follow-up time from the initiation of CIRT was 21.4 months. The 1- and 2-year OS were 84.2 and 55.3%, respectively. The median survival were 24.2 months. The 1- and 2-year PFS were 40.7 and 14.8%, respectively, with a median PFS of 9.9 months. The 1- and 2-year LC were 100 and 50.2 %, respectively. 4 patients experienced grade 3 acute toxicities: hematologic toxicity in 2 patients, anorexia in 1 patient and gastric ulcer/bleeding in 1 patient. The patients with grade 3 gastric ulcer/bleeding underwent blood transfusion and recovered quickly. There was no grade 4 or 5 acute toxicity. In terms of late toxicity, no grade 3 or greater toxicity was observed. CIRT for postoperative locoregional recurrence of pancreatic cancer resulted in relatively long survival with acceptable toxicity. CIRT may be one of the choices of treatment for patients with this disease.

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.

Oncology

The February 2023 Oncology Roundup360 looks at: Is the number of national database research studies in musculoskeletal sarcoma increasing, and are these studies reliable?; Re-excision after unplanned excision of soft-tissue sarcoma is associated with high morbidity; Adjuvant radiation in atypical lipomatous tumours; The oncological outcomes of isolated limb perfusion and neoadjuvant radiotherapy in soft-tissue sarcoma patients - a nationwide multicentre study; Can low-grade chondrosarcoma be treated with intralesional curettage and cryotherapy?; Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis; Doxorubicin-polymeric meshes prevent local recurrence after sarcoma resection while avoiding cardiotoxicity; How important are skip lesions in Ewing’s sarcoma?; Improving outcomes for amputees: the health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees.

Long-term outcomes of octogenarian pancreatic cancer patients treated with carbon ion radiotherapy

BackgroundPancreatic cancer is a disease of the elderly; patients >65 years are 60% of the cases. Due to multiple comorbidities, treating these patients is challenging. We report the efficacy and safety of carbon ion radiotherapy (C-ion RT) in octogenarians. MethodsWe retrospectively analyzed the cases of 46 pancreatic cancer patients aged ≥80 years (median 83, range 80–97) treated with definitive C-ion RT in 2007–2018 at our institute. ResultsTwenty-five patients (54%) had resectable or borderline-resectable disease; none underwent surgery (because of medical reasons, e.g., age, multiple comorbidities). C-ion RT was delivered with a median dose of 55.2 Gy (RBE) in 12 fractions. The survivors' median follow-up period was 43 (range 19–76) months. The entire cohort's median overall survival (OS) was 15 (95%CI: 14–22) months with a 3-year OS of 20% (95%CI: 11%–35%). On both univariate and multivariate analyses, baseline CA19-9 remained the significant independent OS prognostic factor (p = 0.032). The 3-year local control rate for all patients was 34% (95%CI: 19%–53%). Local failure (n = 25, 54%) was as common as distant relapse (n = 26, 57%); 33% of the patients experienced both local and systemic failure. About 15% underwent re-C-ion RT for infield recurrence; they achieved a median 22-month OS. No patients exhibited grade ≥3 severe acute or late toxicities (including those who received re-C-ion RT). ConclusionsC-ion RT in octogenarians with pancreatic cancer showed promising outcomes with acceptable acute and late toxicities and can be considered a reasonable alternative to radical surgery.

Carbon-ion Radiotherapy for Inoperable Head and Neck Bone and Soft-tissue Sarcoma: Prospective Observational Study.

Bone and soft-tissue sarcomas of the head and neck have very poor prognoses. This prospective study aimed to investigate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for bone and soft-tissue sarcoma of the head and neck. The present study was a prospective clinical study that included 10 consecutive patients diagnosed with bone and soft-tissue sarcoma of the head and neck who were treated with C-ion RT between 2012 and 2018 at our institution. C-Ion RT consisted of 70.4 Gy (relative biological effectiveness) in 16 fractions. The 3-year local control, overall survival, and progression-free survival rates for patients overall were 72.9%, 77.8%, and 36%, respectively. The present study demonstrated the efficacy of C-ion RT for bone and soft-tissue sarcoma of the head and neck; adverse events were within the expected range.

Evaluation of Safety for Scanning Carbon-Ion Radiotherapy in Hemodialysis Patients With Prostate Cancer.

Background/AimThe efficacy and safety of carbon-ion radiotherapy (CIRT) for prostate cancer have already been demonstrated. The number of hemodialysis (HD) patients is increasing. Although the toxicity of CIRT in HD patients may be more severe, it has been insufficiently investigated. Therefore, we retrospectively analyzed the safety of CIRT for HD patients with prostate cancer in the present study.Materials and methodsFive HD patients with prostate cancer who underwent CIRT at the Kanagawa Cancer Center during November 2015-2020 were included in this study. CIRT was delivered by the raster scanning method (sCIRT). Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. The dose-volume histogram (DVH) parameters of the target volume and normal organs were evaluated between initial planning computed tomography (CT) and in-room CT images.ResultsIn the acute phase, Grade 1 genitourinary toxicity was recorded in one patient. In the late phase, Grade 1 genitourinary toxicity was recorded in two patients. No gastrointestinal toxicities were noted during the follow-up period. In-room CT analysis revealed no significant differences among all DVH parameters of the target volume and normal organs when compared with the treatment plan dose.ConclusionsThe safety of sCIRT for prostate cancer in HD patients was investigated in the present study. In-room CT analysis suggested the robustness of the treatment plan. According to the present results, sCIRT for prostate cancer can be safely performed in HD patients.

The role of carbon ion radiotherapy for unresectable locally recurrent rectal cancer: a single institutional experience

BackgroundTreatment for locally recurrent rectal cancer after surgery is still a challenge. With the physical and biological advantages, carbon-ion radiotherapy (CIRT) could be a choice for these patients. The purpose of this study was to investigate the efficacy and safety of CIRT for unresectable locally recurrent rectal cancer in Chinese patients.MethodsDate from 25 patients with unresectable locally recurrent rectal cancer treated by CIRT from July 2015 to April 2019 were analyzed retrospectively. The endpoints of this study were overall survival (OS), local control (LC) and acute and late toxicity.ResultsWith the median follow-up of 19.6 (range 5.1–52.5) months, data of all 25 patients were collected. Median prescribed dose for tumor was 72Gy (relative biologic efficacy (RBE)) (range 48–75.6Gy (RBE)). The LC rates at 1 and 2 years were 90.4 and 71.8%. Overall LC at 1- and 2-year were 76.2 and 30.5% for 9 patients whose prescribed tumor doses of CIRT< 66 Gy (RBE), 100 and 100% for 16 patients whose prescribed doses of CIRT≥66 Gy (RBE). Patients received ≥66 Gy (RBE) had obviously better LC rates than those received < 66 Gy (RBE) (P = 0.001). The OS rates at 1 and 2 years were 82.9 and 65.1%, respectively. No acute toxicity over grade 2 was observed, grade 3 late toxicity were observed in 3 patients: gastrointestinal toxicity (n = 1), neuropathy (n = 1), pelvic infection (n = 1). No Grade 4 or higher toxicity was observed.ConclusionOur study shows that CIRT is effective for unresectable locally recurrent rectal cancer patients with acceptable toxicity.

Long-term outcomes of skull base chordoma treated with high-dose carbon-ion radiotherapy.

BackgroundWe evaluated the long‐term efficacy and safety of carbon‐ion radiotherapy (C‐ion RT) for skull base chordoma, a rare neoplasm.MethodsThirty‐four patients with skull base chordoma who were treated with C‐ion RT were prospectively enrolled and analyzed retrospectively. C‐ion RT was delivered with 60.8 Gy (relative biological effectiveness [RBE]) in 16 fractions at four fractions per week.ResultsThe median follow‐up period was 108 months. The 5‐ and 9‐year local control rates were 76.9% and 69.2%, respectively. The 5‐ and 9‐year overall survival rates were 93.5% and 77.4%, respectively. Regarding grade 3 or more severe late reactions, one patient developed a grade 3 mucosal ulcer, two developed grade 4 ipsilateral optic nerve injuries, and one developed a grade 5 mucosal ulcer at 9 years and 3 months after C‐ion RT.ConclusionC‐ion RT with 60.8 Gy (RBE)/16 fractions is a promising treatment option for inoperable skull base chordoma.

Safety and Efficacy of Carbon-ion Radiotherapy Alone for Stage III Non-small Cell Lung Cancer.

We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC). Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.0 Gy (relative biological effectiveness). The median follow-up was 27.6 months (range=1.6-207.7 months). Two-year local control, progression-free survival (PFS), and overall survival (OS) rates were 73.9%, 38.6%, and 54.9%, respectively. Overall, 1 (2%), 4 (6%), and 1 (2%) patient developed Grade 4 (mediastinal haemorrhage), Grade 3 (radiation pneumonitis), and Grade 3 (bronchial fistula) toxicities, respectively. On univariate analysis, clinical T and N stage and CIRT timing were significant predictors of PFS and OS; clinical target volume was a significant predictor of PFS. CIRT alone is effective with acceptable toxicity for Stage III NSCLC.

Carbon-ion Radiotherapy for Isolated Lymph Node Metastasis After Surgery or Radiotherapy for Lung Cancer.

Purpose: Mediastinal and hilar lymph node metastasis is one of the recurrence patterns after definitive treatment of lung cancer. Salvage radiotherapy (RT) can be a treatment option for lymph node metastasis. However, the usefulness of additional RT remains unclear after surgery or RT for the primary lung tumor. We retrospectively evaluated the efficacy and safety of hypofractionated carbon-ion RT for isolated lymph node metastasis.Methods and Materials: Between April 2013 and August 2016, 15 consecutive patients with isolated lymph node metastasis underwent carbon-ion RT. The pretreatment evaluations confirmed the isolated lymph node metastasis and the absence of local recurrence or distant metastasis, which was oligometastatic disease. The median age was 72 (range, 51–83) years, with 11 male patients. The first treatments for primary lung tumors were carbon-ion RT for 8 patients and surgery for 7 patients. There were 9 adenocarcinomas, 4 squamous cell carcinomas, 1 adenosquamous cell carcinoma, and 1 mucoepidermoid carcinoma. Most patients (93%) were irradiated with 52.8 Gy relative biological effectiveness in 12 fractions for 3 weeks. There were no patients treated with concurrent or adjuvant therapy such as chemotherapy, molecular-targeted therapy, or immunotherapy. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0).Results: The median follow-up for surviving patients was 28 months. One patient experienced local lymph node recurrence, and the 2-year local control rate was 92% for all patients. Distant metastasis was observed in 7 patients, and 2-year progression-free survival rate was 47%. During follow-up, there were 4 deaths from lung cancer, and the 2-year overall survival rate was 75%. There were 2 patients with acute grade 2 esophagitis and 2 with late grade 2 cough, which were improved by conservative therapy. There were no other grade 2 or higher adverse events.Conclusions: Hypofractionated carbon-ion RT showed excellent local control and overall survival without severe toxicities in lung cancer patients with isolated lymph node metastasis after surgery or carbon-ion RT for primary lung tumors. A multi-institutional prospective study is required to establish the efficacy and safety of carbon-ion RT.

Health Technology Assessment of Carbon-ion Beam Radiotherapy: A Systematic Review of Clinical Effectiveness and Safety for 54 Oncological Indications in 12 Tumour Regions.

Due to the unique physical dose distribution of carbon-ion radiotherapy (CIRT), CIRT can be regarded as a novel tumour irradiation technique - potentially advantageous for various tumour types. Yet it is unclear in how far, superiority or inferiority can be claimed when comparing CIRT to standard irradiation. This study aimed to assess the scientific evidence regarding the effectiveness and safety of CIRT. A systematic literature review was performed using the European Network for Health Technology Assessment (EUnetHTA) Core Model® for rapid relative effectiveness assessment. The literature search for clinical outcome studies on CIRT was performed using four databases [Cochrane (Central), Centre for Research and Dissemination (CRD), Embase and OVID MEDLINE]. The Cochrane Risk of Bias Tool (for randomised controlled trials) and the Institute of Health Economics (IHE-18) Checklist (for observational studies) were used to assess the risk of bias of the included studies. The evidence synthesis was restricted to 54 oncological indications in 12 broad tumour regions and studies with a low or moderate risk of bias, published between 2005 and 2017. Twenty-seven studies were eligible for the qualitative synthesis of the evidence regarding the effectiveness and safety of CIRT: One randomised controlled trial that primarily focused on the feasibility of CIRT, three case-control studies, three before- and after- studies with a focus on quality of life, and 20 further studies of case series. Overall, insufficient scientific evidence was found for superiority or inferiority of CIRT when compared to standard irradiation for 13/54 oncologicaI indications in 7/12 tumour regions (skull base tumours, brain cancer, cancer in the ear-nose-throat region, bone and soft-tissue tumours, lung cancer, prostate cancer, gastrointestinal tumours). No scientific evidence was found for the remaining 41/54 oncological indications. CIRT is undoubtedly, theoretically, a promising cancer treatment. To date, however, it lacks randomised controlled trials assessing the long-term effectiveness and harms associated with the use of CIRT. CIRT must be considered as an experimental treatment due to the lack of high-quality clinical research.

Clinical outcomes of carbon‐ion radiotherapy for locally advanced non‐small‐cell lung cancer

The efficacy and safety of carbon‐ion radiotherapy (CIRT) for locally advanced non‐small‐cell lung cancer (LA‐NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA‐NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan‐Meier method. The median age was 75.0 years. Overall, 21 (14.9%), 57 (40.4%), 43 (30.5%) and 20 (14.2%) patients had T1, T2, T3 and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%) and 5 (3.5%) patients had N0, N1, N2 and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%) and 20 (14.2%) patients had stages IIA, IIB, IIIA and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%) and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow‐up periods were 29.3 (1.6‐207.7) and 40.0 (10.7‐207.7) months for all patients and survivors, respectively. Two‐year LC, PFS and OS rates were 80.3%, 40.2% and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%) and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis) and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA‐NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy.

Carbon-ion radiotherapy for locally recurrent rectal cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1404 Rectum

PurposeWe investigated the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally recurrent rectal cancer (LRRC). Patients and methodsData from patients with LRRC treated with C-ion RT from November 2003 to December 2014 at three institutions were retrospectively analyzed. The endpoints of this clinical trial were overall survival (OS), local control (LC), and acute/late toxicity. ResultsA total of 224 patients' data were collected. The prescribed dose was 70.4 Gy (relative biological effectiveness [RBE]-weighted absorbed dose) or 73.6 Gy (RBE) in 16 fractions. The median follow-up period from the initiation of C-ion RT was 62 months (range 6–169 months). The OS rates were 73% (95% confidence interval [CI], 67%–79%) at 3 years and 51% (95%CI 44%–58%) at 5 years. The LC rates were 93% (95%CI 88%–96%) at 3 years, and 88% (95%CI 82%–93%) at 5 years. Grade 3 acute toxicity was observed in three patients: gastrointestinal toxicity (n = 1) and pelvic infection (n = 2). Grade 3 late toxicity was observed in 12 patients: skin reaction (n = 2), gastrointestinal toxicity (n = 2), neuropathy (n = 1), and pelvic infection (n = 7). There was no grade 4 or 5 acute or late toxicity. ConclusionsThis first multi-institutional analysis of C-ion RT for LRRC indicated relatively favorable outcomes with limited toxicities.

A single institutional experience of combined carbon-ion radiotherapy and chemotherapy for unresectable locally advanced pancreatic cancer

PurposeThe aim of this study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for unresectable locally advanced pancreatic cancer (LAPC). Methods and materialsPatients with LAPC treated with definitive C-ion RT between April 2014 and July 2017 were analyzed retrospectively. The prescribed dose was 55.2 Gy (relative biological effectiveness [RBE] weighted absorbed dose) in 12 fractions. Overall survival (OS), local control (LC), progression free survival (PFS), and toxicity were evaluated. ResultsSixty-four patients were enrolled. All patients completed planned course of C-ion RT. The median follow-up time for survivors from the initiation of C-ion RT was 24.4 months (range, 5.1–46.1 months). Median survival time was 25.1 months. Two-year OS, LC, and PFS were 53% (95% confidence interval [CI], 39%–66%), 82% (95% CI, 66%–91%), and 23% (95% CI, 14%–36%), respectively. Four patients experienced acute grade 3 toxicities including 3 gastrointestinal (GI) toxicities. There was no grade 3 or more late toxicity. ConclusionsThe clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis.

Multi-institutional Study of Carbon-ion Radiotherapy for Locally Advanced Pancreatic Cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Study 1403 Pancreas

The aim of this multi-institutional study was to evaluate the efficacy and safety of carbon-ion radiotherapy (C-ion RT) for locally advanced pancreatic cancer (LAPC). Patients with LAPC treated with C-ion RT from April 2012 to December 2014 at 3 institutions were retrospectively analyzed. Patients with pathologically-confirmed invasive ductal adenocarcinoma of the pancreas were eligible. The prescribed dose was 52.8Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated. In total, 72 patients were included in this study. Tumors in the head of the pancreas were seen in 30 patients (42%), while those in the body or tail of the pancreas were seen in 42 patients (58%). Fifty-six patients (78%) received concurrent chemotherapy. The OS rates were 73% (95% confidence interval [CI], 62%-84%) at 1year, and 46% (95% CI, 31%-61%) at 2years with a median OS of 21.5months (95% CI, 11.8-31.2months). The 1- and 2-year DMFS rates were 41% (95% CI, 29%-52%) and 28% (95% CI, 16%-40%), respectively. The 1- and 2-year cumulative incidences of LR were 16% (95% CI, 9%-26%) and 24% (95% CI, 14%-36%), respectively. Nineteen patients (26%) experienced acute grade 3 or 4 hematological toxicities. Two patients (3%) had grade 3 anorexia. Late gastrointestinal (GI) grade 3 toxicity was observed in 1 patient (1%). No patients developed late grade 4 or 5 toxicity. The first multi-institutional analysis of C-ion RT for LAPC indicated relatively favorable outcomes with limited toxicities, especially for tumors not in close proximity to GI tract.

A Retrospective Multicenter Study of Carbon Ion Radiotherapy for Locally Advanced Olfactory Neuroblastomas.

The purpose was to evaluate efficacy and safety of carbon ion radiotherapy (C-ion RT) in patients with locally advanced olfactory neuroblastomas (ONBs). This study was a sub-analysis of the Japan Carbon-Ion Radiation Oncology Study Group Study (1402 HN, UMIN000024473). Clinical data of T4 ONBs treated with C-ion RT at four Institutions between November 2003 and December 2014 were retrospectively reviewed. Twenty-one patients underwent C-ion RT. Seven patients had T4a and 14 had T4b tumours without cervical node metastases. The median follow-up period was 39 (range=5-111) months. The 3-year overall survival and local control rates were 88.4% and 83.0%, respectively. Grade 4 late toxicity was observed in three patients, including ipsilateral optic nerve disorder (n=2) and ipsilateral retinopathy (n=1). C-Ion RT is effective and can be a curative modality for T4 ONBs. Prospective multicenter studies are warranted to confirm these findings.

Carbon-ion radiotherapy for locoregional recurrence after primary surgery for pancreatic cancer

The efficacy and safety of carbon ion radiotherapy (C-ion RT) for locoregional recurrence after surgery for pancreatic cancer were retrospectively evaluated. The results for 30 patients showed that C-ion RT was performed safely with relatively long overall survival, good local control, and minimal toxicity.

A phase II clinical trial of carbon-ion radiotherapy and concurrent S-1 chemotherapy for locally advanced pancreatic cancer.

TPS504 Background: Despite recent advances in chemotherapy and radiotherapy, prognosis of unresectable locally advanced pancreatic cancer (LAPC) patients remains poor. To improve the outcome, a phase I/II clinical trial of carbon-ion radiotherapy (CIRT) with concurrent gemcitabine for LAPC was started in National Institute of Radiological Sciences in Japan.When compared to photon beams, carbon ion beams offer improved dose distribution, enabling us to concentrate a sufficient dose within a target volume while minimizing the dose in the surrounding radiosensitive normal tissue. In addition, carbon ions being heavier than protons provide a higher biological effectiveness, which increases with depth reaching the maximum at the end of the beam’s range. Although CIRT is expected to offer powerful local effect, whereas the potential risk of distant metastasis represent a critical problem for LAPC. To control distant metastases and subsequently prolong patient survival, a more effective systemic treatment might be essential. Recently, S-1 has shown favorable antitumor activity in several clinical trials for pancreatic cancer. Oral S-1 also has a great clinical advantage because the risks of complications associated with intravenous administration are avoided.We considered oral S-1 to be an attractive alternative to gemcitabine in the CIRT for LAPC. Thus, we planned a phase II clinical trial to evaluate the efficacy and safety of CIRT with concurrent S-1, which is the first trial in the world. Methods: Eligibility included pathological confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent S-1 is administered orally twice a day at a dose of 80mg/m2/day for 28 days every 6 weeks. Carbon-ion radiotherapy is prescribed with 55.2GyE at 12 fractions in 3 weeks. The primary endpoint is two year overall survival. Clinical trial information: UMIN000013803.

Carbon Ion Radiotherapy for Unresectable Retroperitoneal Sarcomas

Surgery is the mainstay of treatment for retroperitoneal soft tissue sarcomas (STS), and macroscopic total resection is possible in 50–70% of patients. The 5-year local control and overall survival rates obtained by surgery with/without adjuvant radiotherapy are reported to be approximately 50% and 50%, irrespectively. Due to the high linear energy transfer (LET) and the Bragg peak, carbon ion radiotherapy have been expected to be more effective and safe in the treatment for sarcomas than low LET radiation like photons. We evaluated the effectiveness and safety of carbon ion radiotherapy in patients with unresectable retroperitoneal STS. From 1996 to 2004, 17 (male/female:10/7) patients with retroperitoneal STS, not suited for resection, received carbon ion radiotherapy. Ages ranged from 16 to 64 (median 53 years). Eight patients had primary disease and nine recurrent disease. Histologic diagnoses were as follows: MFH (Malignant fibrous histiocytoma) in 5, liposarcoma in 3, MPNST (Malignant peripheral nerve sheath tumor) in 3, and other in 6 patients. Carbon ion radiotherapy was delivered in 16 fractions over 4 weeks. Four patients were entered onto a phase I/II dose escalation study of carbon ion radiotherapy and the remaining 13 patients a phase II study with fixed doses. Total doses: 52.8 GyE (3.3 GyE/Fr) in 1, 64.0 GyE (4.0 GyE/Fr) in 2, 70.4 GyE (4.4 GyE/Fr) in 12, and.73.6 GyE (4.6 GyE/Fr) in 2 patients. Clinical target volumes ranged between 57 and 1034 cm3 (median 416 cm3). Median survival time was 30 (range: 6–74) months for all patients and all living patients were followed more than 1 year. At 3 and 5 years, actuarial overall survival rates were 73% and 63%. Four patients experienced local recurrence, with time from carbon ion radiotherapy to local recurrence ranging between 3 to 35 months. At 3 years, actuarial local control rate was 63%. No severe acute and late reactions (grade 3–5 according to the RTOG criteria) were observed. Local control and overall survival at 3 yeas in patients with retroperitoneal STS treated by carbon ion radiotherapy are similar to those in reported data on patients treated by surgical resection with/without adjuvant radiotherapy. Despite the higher doses delivered to the tumors and the locally more advanced nature of the patients in this series, no severe toxicities were seen. Carbon ion radiotherapy is suggested to be an effective and safe treatment for retroperitoneal STS, but further experience and longer follow up are needed.

Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas.

To evaluate the tolerance for and effectiveness of carbon ion radiotherapy in patients with unresectable bone and soft tissue sarcomas. We conducted a phase I/II dose escalation study of carbon ion radiotherapy. Fifty-seven patients with 64 sites of bone and soft tissue sarcomas not suited for resection received carbon ion radiotherapy. Tumors involved the spine or paraspinous soft tissues in 19 patients, pelvis in 32 patients, and extremities in six patients. The total dose ranged from 52.8 to 73.6 gray equivalent (GyE) and was administered in 16 fixed fractions over 4 weeks (3.3 to 4.6 GyE/fraction). The median tumor size was 559 cm(3) (range, 20 to 2,290 cm(3)). The minimum follow-up was 18 months. Seven of 17 patients treated with the highest total dose of 73.6 GyE experienced Radiation Therapy Oncology Group grade 3 acute skin reactions. Dose escalation was then halted at this level. No other severe acute reactions (grade > 3) were observed in this series. The overall local control rates were 88% and 73% at 1 year and 3 years of follow-up, respectively. The median survival time was 31 months (range, 2 to 60 months), and the 1- and 3-year overall survival rates were 82% and 46%, respectively. Carbon ion radiotherapy seems to be a safe and effective modality in the management of bone and soft tissue sarcomas not eligible for surgical resection, providing good local control and offering a survival advantage without unacceptable morbidity.