Search

Purpose: Stereotactic body radiation therapy (SBRT) for patients with operable stage I non-small cell lung cancer (NSCLC) is less invasive than surgery. However, differences in lifetime costs and patient outcomes remain unclear. In this study, a cost-utility analysis of SBRT compared with surgery for Japanese patients with operable stage I NSCLC was conducted., Methods and Materials: A partitioned survival model was constructed using each treatment arm's overall survival (OS) and progression-free survival (PFS) data. The data for the SBRT arm were extracted from the Japanese multicenter cohort study, which enrolled 678 medically operable patients with stage I NSCLC, and patient registry data were used for the surgery arm. The 5-year OS rate was 78.2% for SBRT and 74.8% for surgery from both studies. The 5-year PFS rate was 57.0% for SBRT and 63.4% for surgery. The quality of life values of PFS and progressive disease were obtained from domestic and overseas literature (PFS: 0.74, progressive disease: 0.65). The time horizon was set to 10 years. The expected costs and quality-adjusted life years for each treatment group were calculated. All costs are expressed in Japanese yen converted to US dollars (USD)., Results: SBRT was the dominant strategy, reducing treatment costs by 4,443.8 USD and increasing quality-adjusted life years by 0.131 compared with surgery. According to probabilistic sensitivity analysis, the probability of SBRT being dominant and cost-effective was 50.6% and 72.4%, respectively. Under the budget impact analysis, the total savings for the patients with stage I NSCLC in Japan was 6,252,870.0 USD (n = 1,407)., Conclusions: SBRT is a more cost-effective option than surgery in patients with medically operable stage I NSCLC in Japan. Large-scale epidemiologic studies that reflect the latest clinical realities, such as OS/PFS, will be needed to validate this study's robustness., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for locally advanced sinonasal malignant tumors in a multicenter retrospective study (J-CROS 1402 HN)., Methods and Materials: Clinical data were collected for patients who had sinonasal malignant tumors of stage N0-1M0 and received C-ion RT at 4 institutions in Japan between November 2003 and December 2014. Of the 458 patients, 393 had naïve tumors and 65 had recurrent tumors. The tumors were located in the nasal cavity (n = 263), maxillary sinus (n = 109), ethmoid sinus (n = 71), and other locations (n = 15). The histologic types were mucosal melanoma (n = 221, 48%), adenoid cystic carcinoma (n = 122, 27%), squamous cell carcinoma (n = 31, 7%), olfactory neuroblastoma (n = 30, 7%), adenocarcinoma (n = 21, 5%), and other types (n = 33, 7%). Of the 458 patients, 300 (66%) had T4 tumors. All patients received definitive C-ion RT., Results: The median follow-up period was 25.2 months for all patients (range, 1.4-132.3 months). The 2-year overall survival and local control rates were 79.6% and 84.1%, respectively. As analyzed according to histology, the 2-year overall survival rate was 68.0% for mucosal melanoma, 96.8% for adenoid cystic carcinoma, 70.0% for squamous cell carcinoma, 96.7% for olfactory neuroblastoma, and 89.7% for adenocarcinoma. Regarding late toxicities, 17% of patients developed grade 3 and 4 toxicities, of which visual impairment was the most common., Conclusion: The results of our multicenter study have demonstrated that C-ion RT can provide excellent clinical outcomes with acceptable late toxicities in patients who have locally advanced sinonasal malignant tumors., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: 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)., Methods and Materials: 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 52.8 Gy (relative biological effectiveness weighted absorbed dose; RBE) or 55.2 Gy (RBE) in 12 fractions. Overall survival (OS), distant metastasis-free survival (DMFS), local recurrence (LR), and toxicity were evaluated., Results: 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 1 year, and 46% (95% CI, 31%-61%) at 2 years with a median OS of 21.5 months (95% CI, 11.8-31.2 months). 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., Conclusions: 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To retrospectively analyze the treatment outcomes of carbon-ion radiation therapy for adenoid cystic carcinoma (ACC) of the head and neck at 4 active carbon-ion facilities in Japan., Methods and Materials: A total of 289 patients who underwent carbon-ion radiation therapy for histology-proven ACC of the head and neck at 4 institutions in Japan between November 2003 and December 2014 were included in this study., Results: Median patient age was 58 years (range, 12-83 years). Tumor sites included the nasal cavity and paranasal sinuses (42%), nasopharynx and oropharynx (19%), oral cavity (12%), major salivary glands (12%), and others (15%). Tumor classifications were T4 in 200 (69%) patients, T3 in 45 (16%), T2 in 22 (8%), T1 in 15 (5%), and unclassified in 7 (2%). The median total dose was 64 Gy (relative biological effectiveness [RBE]; range, 55.2-70.4 Gy [RBE]) in 16 fractions (range, 12-32 fractions). Median follow-up time was 30 months (range, 2-118 months). The 2-year overall survival, progression-free survival, and local control rates were 94%, 68%, and 88%, respectively. Estimated 5-year overall survival, progression-free survival, and local control rates were 74%, 44%, and 68%, respectively. In all, 43 patients (15%) experienced grade ≥3 late toxicity, of which osteonecrosis of the jaw bone was the most common. Two patients treated for nasopharyngeal ACC died from a bleeding ulcer at the tumor site (grade 5 toxicity)., Conclusions: Carbon-ion radiation therapy seems to be a promising treatment for ACC of the head and neck., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Head and neck (HN) adenocarcinoma is rare, and to date, there have been no reports of prospective studies. We retrospectively evaluated the efficacy and safety of carbon-ion radiation therapy (C-ion RT) for HN adenocarcinoma in institutions in Japan., Methods and Materials: HN adenocarcinoma patients with N0M0 or N1M0 disease who were treated with C-ion RT at institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. We enrolled 47 patients (30 male and 17 female patients; median age, 60 years) with HN adenocarcinoma., Results: Primary sites included the nasal and paranasal sinus in 21 patients, orbit in 11, salivary grand in 7, oral cavity and pharynx in 6, and acoustic organ in 2. Thirty-two patients had T4 tumors, 6 had T3, and 6 had T2. Forty-five patients received a diagnosis of N0 disease, whereas 2 had N1 disease. The median total dose of C-ion RT and the number of fractions were 64.0 Gy (relative biological effectiveness) and 16 fractions, respectively. The median follow-up period was 51 months (range, 6-118 months). The 2- and 5-year overall survival rates were 87.9% and 60.4%, respectively, and the 2- and 5-year local control rates were 83.3% and 79.3%, respectively. Multivariate analysis showed that operability (patients with operable tumors) (P=.045) and fractionation (16 fractions) (P=.010) were significant independent prognostic factors for better overall survival. No grade 5 late morbidities were observed. Grade 4 late morbidities were observed in 4 patients, and all of these grade 4 morbidities were visual impairments. All 4 patients with grade 4 visual impairment had T4 tumors in the nasopharynx or paranasal sinuses, which implied inoperable tumors with orbital or brain invasion., Conclusions: C-ion RT resulted in excellent local control. C-ion RT could become a curative treatment option for HN adenocarcinoma with acceptable toxicities., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study., Methods and Materials: Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled., Results: Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities., Conclusion: Carbon-ion RT is a promising treatment option for MMHN., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival., Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m(2) under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined., Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m(2). The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m(2)) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively., Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC)., Methods and Materials: Eligibility criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients., Results: Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed., Conclusions: Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT)., Methods and Materials: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves., Results: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, ≥42.4 Gy or less), 51.6% vs. 2.0% (V40, ≥0.29 cm(3) or less), 45.8% vs. 2.2% (V30, ≥1.35 cm(3) or less), 42.0% vs. 8.5% (V20, ≥3.62 cm(3) or less), or 25.9% vs. 10.5% (V10, ≥5.03 cm(3) or less)., Conclusions: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer., Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean ± SE., Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% ± 2.98% vs. 59.8% ± 2.56% vs. 60.6% ± 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 ± 2.93 vs. 57.0 ± 3.23 mL/m(2)), LV stroke volume index (38.6 ± 1.56 vs. 29.9 ± 1.60 mL/m(2)), and LV ejection fraction (56.9% ± 1.79% vs. 52.8% ± 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 ± 3.05 vs. 72.4 ± 4.04 vs. 85.4 ± 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 ± 0.54 vs. 4.78 ± 0.43 vs. 4.79 ± 0.50 mm), 9 (6.88 ± 0.45 vs. 5.04 ± 0.38 vs. 5.27 ± 0.47 mm), and 10 (9.22 ± 0.48 vs. 8.08 ± 0.34 vs. 8.19 ± 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference (p < 0.05) after CCRT between the groups., Conclusions: Concurrent chemoradiotherapy for esophageal cancer impairs LVF from an early treatment stage. This impairment is prominent in patients with high LV dose., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer., Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio., Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001)., Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to elucidate the efficacy and optimal method of radiotherapy in the management of solitary extramedullary plasmacytoma occurring in the head and neck regions (EMPHN)., Methods and Materials: Sixty-seven patients (43 male and 24 female) diagnosed with EMPHN between 1983 and 2008 at 23 Japanese institutions were reviewed. The median patient age was 64 years (range, 12-83). The median dose administered was 50 Gy (range, 30-64 Gy). Survival data were calculated by the Kaplan-Meier method., Results: The median follow-up duration was 63 months. Major tumor sites were nasal or paranasal cavities in 36 (54%) patients, oropharynx or nasopharynx in 16 (23%) patients, orbita in 6 (9%) patients, and larynx in 3 (5%) patients. The 5- and 10-year local control rates were 95% and 87%, whereas the 5- and 10-year disease-free survival rates were 56% and 54%, respectively. There were 5 (7.5%), 12 (18%), and 8 (12%) patients who experienced local failure, distant metastasis, and progression to multiple myeloma, respectively. In total, 18 patients died, including 10 (15%) patients who died due to complications from EMPHN. The 5- and 10-year overall survival (OS) rates were 73% and 56%, respectively. Radiotherapy combined with surgery was identified as the lone significant prognostic factor for OS (p = 0.04), whereas age, gender, radiation dose, tumor size, and chemotherapy were not predictive. No patient experienced any severe acute morbidity., Conclusions: Radiotherapy was quite effective and safe for patients with EMPHN. Radiotherapy combined with surgery produced a better outcome according to survival rates. These findings require confirmation by further studies with larger numbers of patients with EMPHN., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: This study was performed to evaluate whether the apparent diffusion coefficient (ADC) of a primary lesion correlates with local failure in primary head-and-neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy or radiotherapy., Methods and Materials: We retrospectively studied 38 patients with primary HNSCC (12 oropharynx, 20 hypopharynx, 4 larynx, 2 oral cavity) treated with chemoradiotherapy or radiotherapy with radiation dose to gross tumor volume equal to or over 60 Gy and who underwent pretreatment magnetic resonance imaging, including diffusion-weighted imaging. Ten patients developed local failure during follow-up periods of 2.0 to 9.3 months, and the remaining 28 showed local control during follow-up periods of 10.5 to 31.7 months. The variables that could affect local failure (age, tumor volume, ADC, T stage, N stage, dose, treatment method, tumor location, and overall treatment time) were analyzed using logistic regression analyses for all 38 patients and for 17 patients with Stage T3 or T4 disease., Results: In univariate logistic analysis for all 38 cases, tumor volume, ADC, T stage, and treatment method showed significant (p < 0.05) associations with local failure. In multivariate analysis, ADC and T stage revealed significance (p < 0.01). In univariate logistic analysis for the 17 patients with Stage T3 or T4 disease, ADC and dose showed significant (p < 0.01) associations with local failure. In multivariate analysis, ADC alone showed significance (p < 0.05)., Conclusions: The results suggest that pretreatment ADC, along with T stage, is a potential indicator of local failure in HNSCC treated with chemoradiotherapy or radiotherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy., Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7-77.3 months)., Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high (>or=0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy., Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy.

Purpose: To analyze retrospectively the risk factors of spinal recurrence in patients with intracranial germinoma and clinical outcomes of patients who developed spinal recurrence., Methods and Materials: Between 1980 and 2007, 165 patients with no evidence of spinal metastases at diagnosis were treated with cranial radiotherapy without spinal irradiation. The median follow-up in all 165 patients was 61.2 months (range, 1.2-260.1 months)., Results: After the initial treatment, 15 patients (9.1%) developed spinal recurrences. Multivariate analysis revealed that large intracranial disease (>/=4 cm) and multifocal intracranial disease were independent risk factors for spinal recurrence. Radiation field, total radiation dose, and the use of chemotherapy did not affect the occurrence of spinal recurrences. Of the 15 patients who experienced spinal recurrence, the 3-year actuarial overall survival and disease-free survival (DFS) rates from the beginning of salvage treatments were 65% and 57%, respectively. In the analysis, presence of intracranial recurrence and salvage treatment modality (radiotherapy with chemotherapy vs. radiotherapy alone) had a statistically significant impact on DFS. The 3-year DFS rate in patients with no intracranial recurrence and treated with both spinal radiotherapy and chemotherapy was 100%, whereas only 17% in patients with intracranial recurrence or treated with radiotherapy alone (p = 0.001)., Conclusion: Large intracranial disease and multifocal intracranial disease were risk factors for spinal recurrence in patients with intracranial germinoma with no evidence of spinal metastases at diagnosis. For patients who developed spinal recurrence alone, salvage treatment combined with spinal radiotherapy and chemotherapy was effective in controlling the recurrent disease.

Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC)., Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues., Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution., Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients.

Purpose: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device., Methods and Materials: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs., Results: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 +/- 1.3 mm to 1.5 +/- 0.5 mm, 2.5 +/- 1.9 mm to 1.1 +/- 0.4 mm, and 6.6 +/- 2.4 mm to 2.6 +/- 1.4 mm in SEBH, SIBH, and DIBH, respectively., Conclusions: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.

Purpose: To analyze the outcomes of patients with early hypopharyngeal cancer treated with radical radiotherapy (RT)., Methods and Materials: Ten institutions combined the data from 115 patients with Stage I-II hypopharyngeal squamous cell carcinoma treated with definitive RT between 1990 and 2001. The median patient age was 67 years; 99 patients were men and 16 were women. Of the 115 patients, 39 had Stage I and 76 had Stage II disease. Conventional fractionation was used in 98 patients and twice-daily RT in 17 patients; chemotherapy was combined with RT in 57 patients. The median follow-up period was 47 months., Results: The overall and disease-specific 5-year survival rate for 95 patients without synchronous malignancies was 66.0% and 77.4%, respectively. The 5-year disease-specific survival rate by T stage was 95.8% for patients with T1 disease and 70.1% for patients with T2 disease (p=0.02). Of the 115 patients, local control with laryngeal voice preservation was achieved in 34 of 39 patients with T1 lesions, including 7 patients successfully salvaged, and in 56 of 76 patients with T2 lesions. Sixty-five patients (56.5%) had synchronous or metachronous cancers. Of the 115 patients, 19 died of hypopharyngeal cancer, 10 died of second primary cancers, and 14 died of other causes during the study and follow-up periods., Conclusions: Patients with early hypopharyngeal cancer tended to have a good prognosis after RT. However, second malignancies had an adverse effect on the overall outcomes of patients with early hypopharyngeal cancer.

Purpose: Early squamous cell carcinoma of the hypopharynx is a rare clinical entity. Our objective was to analyze the outcome of patients with early hypopharyngeal cancer treated with curative radiotherapy or the combination of preoperative radiotherapy with surgery., Methods and Materials: Forty-three patients with Stage I-II hypopharyngeal cancer were initially treated with 30-40 Gy of irradiation with or without chemotherapy. Thirty-two patients (74.4%) who demonstrated a complete response continued to receive further radiotherapy, with a median total dose of 61.2 Gy. Eleven other patients (25.6%) received surgery., Results: Local control with laryngeal voice preservation was achieved in 8 (88.9%) of 9 patients with Stage I disease, and in 23 (67.6%) of 34 patients with Stage II disease. The overall and disease-specific 5-year survival rates for all patients were 70.4% and 89.5%, respectively. The disease-specific survival rates according to the T-category were 100% for patients with T1 disease and 87.2% for patients with T2 disease (p = 0.32). Twenty patients (46.5%) had synchronous or metachronous cancers. Four patients died of hypopharyngeal cancer, and 5 died of second-primary esophageal cancer., Conclusions: A majority of patients with early hypopharyngeal cancer was curable. However, second malignancies influenced the overall outcome of patients with early hypopharyngeal cancer.

Purpose: To evaluate the effectiveness of curative radiotherapy (RT) plus recombinant interleukin-2 (rIL-2) immunotherapy regarding the treatment results for angiosarcoma of the scalp. Curative resection of angiosarcoma of the scalp is usually difficult because of the diffuse, clinically undetectable local spread. RT is a rational therapeutic approach, because a wide region of the dermis can be treated, while sparing the underlying normal tissues. Recently, the effectiveness of immunotherapy with rIL-2 has also been reported in the treatment of angiosarcoma of the scalp., Methods and Materials: The data of 20 patients with angiosarcoma of the scalp treated with curative RT plus rIL-2 immunotherapy between January 1988 and June 2002 were retrospectively analyzed. The total radiation dose was 70.3 +/- 6.9 Gy. The fractions were 2-3 Gy daily, given 5 d/wk. rIL-2 immunotherapy was performed by transcatheter arterial administration in 10 patients, systemic administration in 11 during the course of RT, and intratumoral injection in 10 during and/or after RT; 12 patients received a combination of two. Five patients underwent limited surgery, and concomitant pacilitaxel chemotherapy was also used in 2 patients., Results: The median survival time for overall, local recurrence-free, and distant metastasis-free survival was 36.2, 11.1, and 17.8 months, respectively. Local recurrence developed in 7 patients (35%), 4 of whom also had evidence of distant metastases. An additional 7 patients (35%) developed distant metastases alone. Recurrence within the radiation field was recognized in 2 patients with systemic rIL-2 administration alone (p < 0.05). Arterial or intratumoral administration combined with systemic administration of rIL-2 resulted in better distant metaststasis-free survival rates (p < 0.05)., Conclusion: Curative RT plus rIL-2 immunotherapy provided an efficient, effective means of treating angiosarcoma of the scalp. Arterial or intratumoral administration combined with systemic administration of rIL-2 may prolong survival. Additional studies with detailed treatment protocols are recommended.

Purpose: The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion., Methods and Materials: A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function., Results: The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy., Conclusion: Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use.

Purpose: To evaluate the clinical results of proton radiotherapy for patients with non-small-cell lung cancer (NSCLC)., Materials and Methods: Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0-6.0 Gy), and 76.0 Gy (range 49.0-93.0 Gy), respectively., Results: The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity., Conclusions: Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials.

Purpose: To determine the role of proton therapy in patients with carcinoma of the uterine cervix., Methods and Materials: Between 1983 and 1991, 25 patients with squamous cell carcinoma of the uterine cervix (stages IIB-IVA) were treated with a curative intent by external photon irradiation to the pelvis, followed by proton irradiation to the primary tumor, delivering a median total tumor dose of 86 Gy (range 71 Gy/26 Fr-101 Gy/46 Fr), and were followed for a median period of 139 months (range 11-184 months)., Results: Ten-year overall survival rates for stages IIB and IIIB/IVA patients were 89% and 40%, respectively. Five-year local control rates for stages IIB and IIIB/IVA patients were 100% and 61%, respectively. Four percent of patients experienced severe (Grade 4 or more) late complications in the intestine or urinary bladder at 5 years., Conclusion: External photon and proton therapy is effective for those who are not eligible for intracavitary irradiation, and who otherwise have a poor prognosis. The results show that tumor control, survival, and morbidity are similar to those after conventional therapy.