An Analysis of 20 Cases of Radiation-Associated Sarcoma, Including 4 Cases Treated by Carbon Ion Radiotherapy.

INTRODUCTION: Radiation-associated sarcoma (RAS) is one of the most life-threatening complications associated with the treatment of malignant neoplasms. Because all RAS patients have a history of radiotherapy, there have been no effective treatment options when RAS is not completely resected. METHODS: We retrospectively reviewed 20 RAS patients, including 4 unresectable cases treated by carbon ion radiotherapy (CIRT). RESULTS: The primary diseases targeted by radiotherapy included malignant lymphoma (n = 4), cervical cancer (n = 3), pharyngeal cancer (n = 3), breast cancer (n = 2), lung cancer (n = 1), rectal cancer (n = 1), maxillary cancer (n = 1), synovial sarcoma (n = 1), and benign neoplasms (n = 4). The histological diagnoses of RAS included osteosarcoma (n = 8), leiomyosarcoma (n = 3), undifferentiated pleomorphic sarcoma (n = 3), rhabdomyosarcoma (n = 1), angiosarcoma (n = 1), malignant peripheral nerve sheath tumor (n = 1), spindle cell sarcoma NOS (n = 1), and sarcoma not further specified (n = 2). The median survival time from the diagnosis of RAS was 26 months. Eleven patients underwent surgery. Five of these patients achieved a continuous disease free (CDF) status or showed no evidence disease. Four patients underwent CIRT. One of these patients with leiomyosarcoma achieved a CDF status, and the other patient with osteosarcoma achieved a partial response. On the other hand, 2 patients experienced grade 3 toxicities that required surgical treatment. CONCLUSION: RAS originates from various types of diseases that are treated by radiotherapy and shows diverse pathological features. Complete resection achieves a good prognosis. CIRT can be an effective and feasible option for unresectable RAS.

Carbon ion radiotherapy for sacral chordoma: A retrospective nationwide multicentre study in Japan.

BACKGROUND AND PURPOSE: Usefulness of carbon ion radiotherapy (CIRT) for sacral chordoma has been reported from single institutions. We conducted a retrospective nationwide multicentre study to evaluate the clinical outcomes of CIRT for sacral chordoma in Japan. MATERIALS AND METHODS: A total of 219 patients who underwent CIRT for sacral chordoma at institutions across Japan between December 2003 and July 2014 were included in this study. RESULTS: Median patient age was 67 years (range, 26-87 years). Most patients had no history of surgical resection (96%). The most frequent planning target volume (PTV) range was 100-500 mL (65%). The most frequently used dose-fractionation was 67.2 Gy (relative biological effectiveness) in 16 fractions (65%). The median follow-up was 56 months (range, 7-132 months). The 5-year overall survival (OS), progression-free survival, and local control rates were 84%, 48%, and 72%, respectively. Frequent sites of out-of-field recurrence included bone (9%) and lung (9%) metastases. The Cox proportional hazards model revealed that both younger age (P = 0.004) and smaller PTV (P = 0.001) were associated with significantly better OS. Acute toxicities of ≥Grade 3 occurred in eight patients (4%). Late toxicities of ≥Grade 3 occurred in 13 patients (6%): skin disorders in six patients (3%), pain in three (1%), myositis in three (1%), etc. CONCLUSION: Our retrospective nationwide multicentre study showed that CIRT for sacral chordoma was effective and safe, and replicated the previously reported data from a representative CIRT institution in Japan demonstrating high local control and low toxicity rates.

Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas.

PURPOSE: To evaluate the clinical outcome of combination of carbon-ion radiotherapy with separation surgery (CIRT-SS) in patients with primary spinal/paraspinal sarcoma (PSPS) and epidural spinal cord compression (ESCC). METHODS: CIRT-SS was performed in 11 consecutive patients. Patients treated in the primary and salvage settings were categorized into Group A (n = 8) and Group B (n = 3), respectively. Clinical results and imaging findings were collected, with a particular focus on ESCC grade, treatment-associated adverse events (AEs), and the locoregional control (LRC) rate and overall survival (OS). RESULTS: The median follow-up period from the start of CIRT-SS was 25 months (7-57 months). ESCC was improved by SS in all cases. No patients exhibited radiation-induced myelopathy (RIM), but three developed Grade 3 vertebral compression fracture (VCF) during follow-up. Locoregional recurrences were observed in four patients [Group A: 1 (12.5%), Group B: 3 (100%)]. Over the entire follow-up period, three patients developed distant metastases and two patients died. The 2-year LRC rate and OS were 70% and 80%, respectively. CONCLUSION: CIRT-SS in the primary setting achieved acceptable LRC and OS without RIM in patients with PSPS and with ESCC. VCF was the most frequent AE associated with CIRT-SS.

Post-carbon-ion radiotherapy vertebral pathological fractures in upper cervical primary malignant spinal tumors treated by occipito-cervical fusion.

PURPOSE: To describe the characteristic features of post-carbon-ion radiotherapy (CIRT) vertebral pathological fractures (VPFs) in upper cervical primary malignant spinal tumors (PMSTs) treated by occipito-cervical (OC) fusion. METHODS: OC fusion was performed for three consecutive patients with post-CIRT VPFs. The clinical results and imaging findings, including bone single-photon emission computed tomography (SPECT)/CT were prospectively collected. RESULTS: No surgery-related wound complication and surgical site infection were noted. One patient experienced re-fracture and displacement of dens with the loosening of occipital screws and was treated by posterior revision surgery. At the final follow-up, all patients were alive without evidence of disease, and the solid OC fusion was confirmed. Bone SPECT/CT clearly revealed the effect of CIRT on bone turnover in the irradiated field. CONCLUSION: The OC fusion with autologous bone grafts was a reliable option for the treatment of post-CIRT VPCs in the patients with upper cervical PMSTs. In addition, evaluation of the bone turnover at the irradiated field by bone SPECT/CT would help surgeons select an effective plan of care, such as fusion level and postoperative care.

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

PURPOSE: The 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 MATERIALS: Patients 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. RESULTS: Sixty-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. CONCLUSIONS: The clinical results of C-ion RT for LAPC at our institution were comparable to those of a recent multi-institutional analysis.

Carbon-ion radiotherapy for patients with advanced stage non-small-cell lung cancer at multicenters.

Carbon-ion radiation therapy (CIRT) for advanced non-small-cell lung cancer (NSCLC) has not been well studied to date. This paper aimed to analyze a retrospective multicenter survey for detecting problems with the use of CIRT for Stage II and III NSCLC (7th UICC TNM Staging System). Inclusion was restricted to patients with Stage II and III NSCLC who received CIRT from November 2003 to December 2014. We gathered the data from three CIRT operating centers on July 2015. Patients with radiotherapy history, patients with cancers other than lung cancer, and those receiving palliative therapies were excluded. The patient characteristics, prescribed dose/fraction, survival rates, and adverse effects were analyzed. The total number of patients was 64 (male: 49, female: 15). Of these, 53 patients were medically inoperable. The median age was 76 years (range 46-91), and the median follow-up period was 18.5 months (range 3.2-121.5). The clinical staging consisted of 10 Stage IIA, 30 Stage IIB, 23 Stage IIIA and 1 Stage IIIB. The median prescribed dose was 72.0 Gy (RBE) (range 52.8-72.0) in 16 fractions (range 4-16). The 2-year overall survival, progression-free survival, and local control rates were 62.2% [confidence interval (CI): 47.5-76.9], 42.3% (CI: 28.8-55.8) and 81.8% (CI: 69.9-94.0), respectively. There were no higher than Grade 2 adverse effects observed. CIRT for inoperable Stage II and III NSCLC could be implemented without severe adverse effects, but the clinical staging (including lymph node status) was inhomogeneous. In addition, the prescribed dose and fractionation were not standardized. Further data accumulation and a multiple centers prospective trial for evaluating clinical stage-based results are required.

Dosimetric analysis of upper gastrointestinal ulcer after carbon-ion radiotherapy for pancreatic cancer.

PURPOSE: The aim of this study was to clarify the incidence, clinical risk factors, and dose-volume relationship of upper gastrointestinal (GI) ulcer after carbon-ion radiotherapy (C-ion RT) for pancreatic cancer. MATERIALS AND METHODS: Fifty-eight pancreatic cancer patients were treated with C-ion RT from April 2014 to December 2015. The total dose was 55.2Gy (RBE) in 12 fractions. D2cm3 of GI tracts were restricted under 46Gy (RBE); RBE-weighted absorbed dose. The association between dosimetric parameters (V10-50, Dmax, D1cm3, D2cm3) and GI ulcer was examined using Spearman's correlation. The incidence of GI ulcer was compared between the two groups divided by the cutoff value. RESULTS: Twelve patients (21%) experienced gastric ulcer including only one (2%) grade 3 ulcer. There was no grade 4/5 toxicity or duodenal ulcer. V10-30 was significantly associated with gastric ulcer. The 1-year estimated risk of gastric ulcer for the determined cutoff values were 51% vs. 10% (V10, ⩾102cm(3) or less), 42% vs. 9% (V20, ⩾24cm(3) or less), 34% vs. 4% (V30, ⩾6cm(3) or less). CONCLUSIONS: The incidence of GI ulcer after C-ion RT was very low with the dose constraint of D2cm3 <46Gy (RBE). To further minimize the risk of GI ulcer, V10-30 should also be reduced.

Particle radiotherapy for prostate cancer.

Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

Impact of carbon ion radiotherapy for unresectable osteosarcoma of the trunk.

BACKGROUND: The authors summarized the outcomes of patients with unresectable osteosarcoma of the trunk who received carbon ion radiotherapy (CIRT). METHODS: The authors performed a retrospective analysis of 78 patients who had medically inoperable osteosarcoma of the trunk and received treatment with CIRT between 1996 and 2009. Tumor sites included the pelvis in 61 patients, the spine and paraspinal region in 15 patients, and other sites in 2 patients. The median applied CIRT dose was 70.4 Gray equivalent (GyE) in a total of 16 fixed fractions over 4 weeks. RESULTS: The minimum duration of follow-up for survivors was 14 months. Forty-eight patients remained alive. The 5-year overall survival rate was 33%, and the local control rate was 62%. Thirty-eight patients who had a clinical target volume <500 cm(3) had a 5-year overall survival rate of 46% and a 5-year local control rate of 88%. Except for 3 patients who experienced severe skin/soft tissue complications requiring skin grafts, no other severe toxicities were observed. Of 9 patients who were continuously disease free for >5 years, 8 were able to walk with or without the help of a cane, and 6 were free from pain killers. CONCLUSIONS: CIRT appeared to be a safe and effective modality for the management of unresectable osteosarcoma of the trunk, providing good local control and offering a survival advantage and good long-term functional results without unacceptable morbidity.

[High-dose-rate brachytherapy with external beam radiotherapy for localized or locally advanced prostate cancer].

PURPOSE: To evaluate the therapeutic outcomes and late toxicities in patients treated by high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT) for localized or locally advanced prostate cancer. MATERIALS AND METHODS: From May 2004 to September 2008, 86 men were treated by HDR-BT with EBRT for localized or locally advanced prostate cancer at the National Hospital Organization Kyushu Medical center. The median EBRT and HDR-BT doses were 40 Gy and 30 Gy, respectively. RESULT: With a median follow-up of 24 months, the 3-year overall, disease specific, and biochemical relapse-free survival rates in all patients were 97.3%, 100%, and 83.6% respectively. The 3-year biochemical relapse-free survival rate of the patients categorized to low or intermediate risk group (91.8%) was significantly better than that of the patients categorized to the high risk group (74.3%) (p = 0.042). There was no significant difference of biochemical relapse-free survival regarding to the other clinical factors (age, T-stage, Gleason score, initial prostate-specific antigen level, neoadjuvant hormone therapy, and total dose of EBRT and HDR-BT). Late Grade2 and Grade3 gastrointestinal toxicities were observed in 8 patients (9.3%) and 2 patients (2.3%), respectively. Late Grade2 genitourinary toxicities were observed in 12 patients (13.9%). There was no patient suffered from late Grade3 or greater genitourinary toxicities. CONCLUSION: HDR-BT with EBRT can be safe and effective for localized or locally advanced prostate cancer.