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.

Observer uncertainties of soft tissue-based patient positioning in IGRT.

PURPOSE: There remain uncertainties due to inter- and intraobserver variability in soft-tissue-based patient positioning even with the use of image-guided radiation therapy (IGRT). This study aimed to reveal observer uncertainties of soft-tissue-based patient positioning on cone-beam computed tomography (CBCT) images for prostate cancer IGRT. METHODS: Twenty-six patients (7-8 fractions/patient, total number of 204 fractions) who underwent IGRT for prostate cancer were selected. Six radiation therapists retrospectively measured prostate cancer location errors (PCLEs) of soft-tissue-based patient positioning between planning CT (pCT) and pretreatment CBCT (pre-CBCT) images after automatic bone-based registration. Observer uncertainties were evaluated based on residual errors, which denoted the differences between soft-tissue and reference positioning errors. Reference positioning errors were obtained as PCLEs of contour-based patient positioning between pCT and pre-CBCT images. Intraobserver variations were obtained from the difference between the first and second soft-tissue-based patient positioning repeated by the same observer for each fraction. Systematic and random errors of inter- and intraobserver variations were calculated in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions. Finally, clinical target volume (CTV)-to-planning target volume (PTV) margins were obtained from systematic and random errors of inter- and intraobserver variations in AP, SI, and LR directions. RESULTS: Interobserver variations in AP, SI, and LR directions were 0.9, 0.9, and 0.5 mm, respectively, for the systematic error, and 1.8, 2.2, and 1.1 mm, respectively, for random error. Intraobserver variations were <0.2 mm in all directions. CTV-to-PTV margins in AP, SI, and LR directions were 3.5, 3.8, and 2.1 mm, respectively. CONCLUSION: Intraobserver variability was sufficiently small and would be negligible. However, uncertainties due to interobserver variability for soft-tissue-based patient positioning using CBCT images should be considered in CTV-to-PTV margins.

Carbon-ion radiotherapy for lymph node oligo-recurrence: a multi-institutional study by the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS).

BACKGROUND: The efficacy of carbon-ion radiotherapy (C-ion RT) for lymph node (LN) oligo-recurrence has only been evaluated in limited single-center studies. We aimed to investigate the benefit of C-ion RT for LN oligo-recurrence in a large multi-center study. METHODS: Patients who received C-ion RT between December 1996 and December 2015 at 4 participating facilities and who met the following eligibility criteria were included: (i) histological or clinical diagnosis of LN recurrence; (ii) controlled primary lesion; (iii) no recurrence other than LN; (iv) LN recurrence involved in a single lymphatic site; and (v) age ≥ 20 years. RESULTS: A total of 323 patients were enrolled. Median follow-up period was 34 months for surviving patients. The most common dose fractionation of C-ion RT was 48.0 Gy (relative biological effectiveness) in 12 fractions. Forty-seven patients had a history of RT at the recurrent site. The 2-year local control (LC) and overall survival (OS) rates after C-ion RT were 85% and 63%, respectively. Only 1 patient developed grade-3 toxicity. Factors such as LN diameter, histology, and history of previous RT did not correlate with LC. Smaller diameters (< 30 mm) and numbers (≤ 3) of LN metastases as well as longer disease-free intervals post-primary therapy (≥ 16 months) were associated with significantly better OS. CONCLUSIONS: C-ion RT for LN oligo-recurrence appeared to be effective and safe. C-ion RT may provide a survival benefit to patients with LN oligo-recurrence, particularly to those with few LN metastases, smaller LN diameters, and longer disease-free intervals.

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 retrospective multicenter study of carbon-ion radiotherapy for major salivary gland carcinomas: Subanalysis of J-CROS 1402 HN.

A retrospective multicenter study was carried out to assess the clinical outcomes of carbon-ion radiotherapy for head and neck malignancies (Japan Carbon-Ion Radiation Oncology Study Group [J-CROS] study: 1402 HN). We evaluated the safety and efficacy of carbon-ion radiotherapy in patients with major salivary gland carcinoma. Sixty-nine patients treated with carbon-ion radiotherapy at four Japanese institutions were analyzed. Thirty-three patients (48%) had adenoid cystic carcinomas, 10 (14%) had mucoepidermoid carcinomas, and 26 (38%) had other disease types. Three patients (4%) had T1 disease, 8 (12%) had T2, 25 (36%) had T3, and 33 (48%) had T4. The median radiation dose was 64 Gy (relative biological effectiveness) in 16 fractions. The median gross tumor volume was 27 mL. The median follow-up period was 32.7 months. The 3-year local control rate and overall survival rate were 81% and 94%, respectively. Regarding acute toxicities, seven patients had grade 3 mucositis and seven had grade 3 dermatitis. Regarding late toxicities, one patient had grade 3 dysphagia and one had a grade 3 brain abscess. No grade 4 or worse late reactions were observed. In conclusion, definitive carbon-ion radiotherapy was effective with acceptable toxicity for major salivary gland carcinomas.

Short-course carbon-ion radiotherapy for hepatocellular carcinoma: A multi-institutional retrospective study.

BACKGROUND & AIMS: Carbon-ion radiation therapy has shown encouraging results in hepatocellular carcinoma patients in single-centre studies. We evaluated the effectiveness and safety of short-course carbon-ion radiation therapy for hepatocellular carcinoma in a multicentre study conducted by the Japan Carbon Ion Radiation Oncology Study Group. METHODS: Consecutive hepatocellular carcinoma patients who were treated with carbon-ion radiation therapy in four or fewer fractions at four Japanese institutions between April 2005 and November 2014 were analysed retrospectively. The primary outcome was overall survival; secondary outcomes were local control rate, treatment-related toxicity and radiation-induced liver disease. RESULTS: A total of 174 patients were included in this study. Prescribed carbon-ion radiation therapy doses were (relative biological effectiveness): 48.0 Gy in two fractions (n = 46), and 52.8 Gy (n = 108) and 60.0 Gy (n = 20) in four fractions. The median follow-up period was 20.3 (range, 2.9-103.5) months. The overall survival and local control rates at 1, 2 and 3 years were 95.4%, 82.5% and 73.3%; and 94.6%, 87.7% and 81.0% respectively. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status 1-2, Child-Pugh class B, maximum tumour diameter ≥3 cm, multiple tumours and serum alpha foetoprotein level >50 ng/mL were significant prognostic factors of overall survival. No treatment-related death occurred during the follow-up period. Grades 3 or 4 treatment-related toxicities were observed in 10 patients (5.7%); radiation-induced liver disease was observed in three patients (1.7%). CONCLUSIONS: Short-course carbon-ion radiation therapy is a safe, effective and potentially curative therapy for hepatocellular carcinoma.

Final report of survival and late toxicities in the Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702).

PURPOSE: A dose escalation study to determine the recommended dose with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (JCOG0702) was conducted. The purpose of this paper is to report the survival and the late toxicities of JCOG0702. MATERIALS AND METHODS: The continual reassessment method was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose. The starting dose was 40 Gy in four fractions at D95 of PTV. RESULTS: Twenty-eight patients were enrolled. Ten patients were treated with 40 Gy at D95 of PTV, four patients with 45 Gy, eight patients with 50 Gy, one patient with 55 Gy and five patients with 60 Gy. Ten patients were alive at the last follow-up. Overall survival (OS) for all patients was 67.9% (95% CI 47.3-81.8%) at 3 years and 40.8% (95% CI 22.4-58.5%) at 5 years. No Grade 3 or higher toxicity was observed after 181 days from the beginning of the SBRT. Compared to the toxicities up to 180 days, chest wall related toxicities were more frequent after 181 days. CONCLUSIONS: The 5-year OS of 40.8% indicates the possibility that SBRT for peripheral T2N0M0 non-small cell lung cancer is superior to conventional radiotherapy. The effect of the SBRT dose escalation on OS is unclear and further studies are warranted.

Multi-institutional retrospective study of mucoepidermoid carcinoma treated with carbon-ion radiotherapy.

This study aimed to evaluate the clinical outcomes of patients with mucoepidermoid carcinomas in the head and neck treated with carbon-ion radiotherapy. Data from 26 patients who underwent carbon-ion radiotherapy in four facilities were analyzed in this multi-institutional retrospective study: the Japan Carbon-ion Radiation Oncology Study Group. The median follow-up time was 34 months. One patient experienced local recurrence, and the 3-year local control rate was 95%. One patient developed lymph node recurrence and five developed distant metastases. The 3-year progression-free survival rate was 73%. Five patients died, two of mucoepidermoid carcinoma and three of intercurrent disease. The 3-year overall survival rate was 89%. Acute mucositis and dermatitis of grade 3 or higher were experienced by 19% and 8% of patients, respectively; these improved with conservative therapy. Late mucositis and osteonecrosis of jaw were observed in 12% and 23% of patients, respectively. The 3-year cumulative rate of any late adverse event of grade 3 or higher was 14%. None of the patients died of the acute or late adverse events. Carbon-ion radiotherapy was efficacious and safe for treating mucoepidermoid carcinoma in this multi-institutional retrospective study (registration no. UMIN000024473). We are currently undertaking a prospective multicenter study.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

BACKGROUND: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). METHODS: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. RESULTS: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. CONCLUSIONS: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Oligo-recurrence predicts favorable prognosis of brain-only oligometastases in patients with non-small cell lung cancer treated with stereotactic radiosurgery or stereotactic radiotherapy: a multi-institutional study of 61 subjects.

BACKGROUND: To investigate the prognostic value of oligo-recurrence in patients with brain-only oligometastases of non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). METHODS: Patients treated with SRS or SRT for brain-only NSCLC oligometastases in 6 high-volume institutions in Japan between 1996 and 2008 were reviewed. Eligible patients met 1), 2), and 4) or 1), 3), and 4) of the following: 1) NSCLC with 1 to 4 brain metastases on magnetic resonance imaging (MRI) treated with SRS or SRT; 2) control of the primary lesions (thorax) at the time of SRS or SRT for brain metastases (patients meeting this criterion formed the oligo-recurrence group); 3) with SRS or SRT for brain metastases, concomitant treatment for active primary lesions (thorax) with curative surgery or curative stereotactic body radiotherapy (SBRT), or curative chemoradiotherapy (sync-oligometastases group); and 4) Karnofsky performance status (KPS) ≥70. RESULTS: The median overall survival (OS) of all 61 patients was 26 months (95 % CI: 17.5-34.5 months). The 2-year and 5-year overall survival rates were 60.7 and 15.7 %, respectively. Stratified by oligostatus, the sync-oligometastases group achieved a median OS of 18 months (95 % CI: 14.8-21.1 months) and a 5-year OS of 0 %, while the oligo-recurrence group achieved a median OS of 41 months (95 % CI: 27.8-54.2 months) and a 5-year OS of 18.6 %. On multivariate analysis, oligo-recurrence was the only significant independent factor related to a favorable prognosis (hazard ratio: 0.253 (95 % CI: 0.082-0.043) (p = 0.025). CONCLUSIONS: The presence of oligo-recurrence can predict a favorable prognosis of brain-only oligometastases in patients with NSCLC treated with SRS or SRT.

Clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy for lung tumors.

BACKGOUND: We retrospectively investigated the clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Between April 2003 and July 2012, 473 patients with lung tumors were treated with SBRT. We identified 12 patients (2.5 %) with pneumothorax caused by SBRT, and evaluated the clinical features of pneumothorax. RESULTS: All of the tumors were primary lung cancers. The severity of radiation pneumonitis was grade 1 in 10 patients and grade 2 in two patients. Nine patients had emphysema. The planning target volume and pleura overlapped in 11 patients, and the tumors were attached to the pleura in 7 patients. Rib fractures were observed in three patients before or at the same time as the diagnosis of pneumothorax. The median time to onset of pneumothorax after SBRT was 18.5 months (4-84 months). The severity of pneumothorax was grade 1 in 11 patients and grade 3 in one patient. CONCLUSION: Although pneumothorax was a relatively rare late adverse effect after SBRT, some patients demonstrated pneumothorax after SBRT for peripheral lung tumors. Although most pneumothorax was generally tolerable and self-limiting, careful follow-up is needed.

Stereotactic body radiation therapy for primary lung cancers clinically diagnosed without pathological confirmation: a single-institution experience.

BACKGROUND: Pathological diagnosis of small lung lesions is sometimes difficult in medically inoperable patients. The purpose of this study was to evaluate the adverse events and the outcomes of stereotactic body radiation therapy (SBRT) for lung lesions which were clinically diagnosed as primary lung cancer without pathological confirmation. METHODS: Between April 2003 and April 2011, 88 patients with small lung lesions which were clinically diagnosed as primary lung cancer were treated with SBRT. The median tumor size was 19 mm (range 8-40 mm). The radiation dose was 48 Gy in four fractions in all patients. The median follow-up was 23 months (range 6-91 months). RESULTS: Recurrence was observed in 13 patients. The local control rate, progression-free survival rate, and overall survival rate at 3 years were 90, 67, and 80 %, respectively. Two patients (2.3 %) had Grade 2 radiation pneumonitis, and six patients (6.8 %) had Grade 2 rib fractures. There were no adverse events of Grade 3 or greater. CONCLUSIONS: SBRT appears to be a safe and effective treatment option for small lung lesions that are clinically diagnosed as primary lung cancer without pathological confirmation.

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.

Recent advances in radiation oncology: intensity-modulated radiotherapy, a clinical perspective.

Radiotherapy plays an important role in the treatment of various malignancies, and intensity-modulated radiotherapy (IMRT) is an attractive option because it can deliver precise conformal radiation doses to the target while minimizing the dose to adjacent normal tissues. IMRT provides a highly conformal dose distribution by modulating the intensity of the radiation beam. A number of malignancies have been targeted by IMRT; this work reviews published data on the major disease sites treated with IMRT. The dosimetric advantage of IMRT has resulted in the significant reduction of adverse effects in some tumors. However, there are few clinical trials comparing IMRT and three-dimensional conformal radiotherapy (3D-CRT), and no definite increase in survival or the loco-regional control rate by IMRT has been demonstrated in many malignancies. IMRT also requires greater time and resources to complete compared to 3D-CRT. In addition, the cost-effectiveness of IMRT versus 3D-CRT has not yet been established.

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG).

INTRODUCTION: The standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. METHODS: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. RESULTS: The median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1-89.2), 91.2% (95% CI: 86.0-96.8), 65.9% (95% CI: 58.2-74.6), and 95.8% (95% CI: 92.3-99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. CONCLUSIONS: This study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

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.

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 patiets 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.

Phase 1 trial of preoperative, short-course carbon-ion radiotherapy for patients with resectable pancreatic cancer.

BACKGROUND: The authors evaluated the tolerance and efficacy of carbon-ion radiotherapy (CIRT) as a short-course, preoperative treatment and determined the recommended dose needed to reduce the risk of postoperative local recurrence without excess injury to normal tissue. METHODS: Patients radiographically defined with potentially resectable pancreatic cancer were eligible. A preoperative, short-course, dose-escalation study was performed with fixed 8 fractions in 2 weeks. The dose of irradiation was increased by 5% increments from 30 grays equivalents (GyE) to 36.8 GyE. Surgery was to be performed 2 to 4 weeks after the completion of CIRT. RESULTS: The study enrolled 26 patients. At the time of restaging after CIRT, disease progression with distant metastasis or refusal ruled out 5 patients from surgery. Twenty-one of 26 patients (81%) patients underwent surgery. The pattern of initial disease progression was distant metastasis in 17 patients (65%) and regional recurrence in 2 patients (8%). No patients experienced local recurrence. The 5-year survival rates for all 26 patients and for those who underwent surgery were 42% and 52%, respectively. CONCLUSIONS: Preoperative, short-course CIRT followed by surgery is feasible and tolerable without unacceptable morbidity.

Impact of carbon ion radiotherapy for primary spinal sarcoma.

BACKGROUND: Spinal sarcomas have been one of the most challenging diseases for orthopedic surgeons. The objective of this study was to retrospectively analyze carbon ion radiotherapy (CIRT) treatment results for spinal sarcoma. METHODS: Forty-seven patients with 48 medically unresectable spinal sarcomas, excluding sacral tumors, received treatment with CIRT between 1996 and 2011. All patients were enrolled in phase 1/2 and phase 2 clinical trials of CIRT for bone and soft tissue sarcoma. The applied dose ranged from 52.8 gray equivalents (GyE) to 70.4 GyE (median, 64.0 GyE) in 16 fixed fractions over 4 weeks. RESULTS: The median patient age was 54 years, and the cohort included 24 men and 23 women. Thirty-five patients were without prior treatment, and 12 patients had locally recurrent tumors after previous resection. The median follow-up was 25 months, and the median survival was 44 months (range, 5.2-148 months). The 5-year local control, overall survival, and progression free rates were 79%, 52%, and 48%, respectively. None of the 15 patients who had tumors measuring <100 cm(3) had a local recurrence. No fatal toxicities occurred during follow-up. One patient each had a grade 3 late skin reaction and a grade 4 late skin reaction. Vertebral body compression was observed in 7 patients. One patient had a grade 3 late spinal cord reaction. Twenty-two of the surviving 28 patients who had primary tumors remained ambulatory without supportive devices. CONCLUSIONS: CIRT appears to be both effective and safe for the treatment of patients with unresectable spinal sarcoma.

Treatment outcome of high-dose-rate interstitial radiation therapy for patients with stage I and II mobile tongue cancer.

OBJECTIVES: The aim of the study was to investigate the outcomes of high-dose-rate interstitial radiation therapy for patients with Stage I and II mobile tongue cancer retrospectively. METHODS: Sixty-seven patients with Stage I and II mobile tongue cancer were treated with high-dose-rate interstitial radiation therapy, with or without external beam radiation therapy, between 1997 and 2007. The median dose of interstitial radiation therapy was 50 Gy in 10 fractions over 6 days. Thirty-five patients received external beam radiation therapy before interstitial radiation therapy. The median dose of external beam radiation therapy was 20 Gy delivered with single-lateral or bilateral fields, including the primary tumor site and upper jugular lymph nodes. Thirty-seven patients received concurrent chemotherapy, including carboplatin, cisplatin, fluorouracil or tegafur, gimeracil and oteracil (TS-1) systemically or with intra-arterial injection. Thirty-three patients received intratumoral injection of bleomycin before catheter insertion. The median follow-up time was 58.6 months (range 15.1-102.4 months). RESULTS: The 5-year overall, cause-specific, progression-free survival rate and local control rate were 88.7, 92.1, 76.0 and 94.0%, respectively. Fourteen patients developed cervical lymph node recurrence, 11 of which were distributed within the external beam radiation therapy field. We found local failures in four cases within 2 years after the treatment and in three cases after >7 years, even though the latter were difficult to distinguish from second primary cancers. CONCLUSIONS: The treatment results of our institutions were equivalent to previous reports. Most cervical lymph node metastases occurred within the external beam radiation therapy field, which implied that the external beam radiation therapy dose of 20-30 Gy was insufficient to prevent late cervical lymph node metastases.