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This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41–88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76–1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.

Anti-cancer treatments for lung cancer patients with interstitial lung disease (ILD) are challenging. The treatment options for ILD are often limited because of concerns that treatments can cause acute exacerbation (AE) of ILD. This study aimed to analyze the outcomes of carbon-ion radiotherapy (CIRT) for stage I non-small cell lung cancer (NSCLC) with ILD, using a multi-institutional registry. Patients with ILD who received CIRT for stage I NSCLC in CIRT institutions in Japan were enrolled. The indication for CIRT was determined by an institutional multidisciplinary tumor board, and CIRT was performed in accordance with institutional protocols. Thirty patients were eligible. The median follow-up duration was 30.3 months (range, 2.5–58 months), and the total dose ranged from 50 Gy (relative biological effectiveness [RBE]) to 69.6 Gy (RBE), and five different patterns of fractionation were used. The beam delivery method was passive beam in 19 patients and scanning beam in 11 patients. The 3-year overall survival (OS), cause-specific survival, disease-free survival (DFS) and local control (LC) rates were 48.2%, 62.2%, 41.2% and 88.1%, respectively. Grade > 2 radiation pneumonitis occurred in one patient (3.3%). In conclusion, CIRT is a safe treatment modality for stage I NSCLC with concomitant ILD. CIRT is a safe and feasible treatment option for early lung cancer in ILD patients.

Background and purpose We aimed to determine the risk factors for radiation-induced brain injury (RIBI 1 ) after carbon ion radiotherapy (CIRT) to predict their probabilities in long-term survivors. Materials and methods We evaluated 104 patients with head, neck, and skull base tumors who underwent CIRT in a regimen of 32 fractions and were followed up for at least 24 months. RIBI was assessed using the Common Terminology Criteria for Adverse Events. Results The median follow-up period was 45.5 months; 19 (18.3 %) patients developed grade ≥2 RIBI. The maximal absolute dose covering 5 mL of the brain (D5ml) was the only significant risk factor for grade ≥2 RIBI in the multivariate logistic regression analysis (p = 0.001). The tolerance doses of D5ml for the 5% and 50% probabilities of developing grade ≥2 RIBI were estimated to be 55.4 Gy (relative biological effectiveness [RBE]) and 68.4 Gy (RBE) by a logistic model, respectively. Conclusion D5ml was most significantly associated with grade ≥2 RIBI and may enable the prediction of its probability.

Curative treatment for hepatocellular carcinoma (HCC) is limited to hepatic resection (HR), radiofrequency ablation, and liver transplantation, while the value of particle therapy (PT) as an initial treatment remains unclear. This study aimed to compare the outcomes of HR and PT for single HCC.A total of 554 patients with single HCC without vascular invasion were enrolled from January 2000 to December 2015. Patients underwent either HR (n = 279) or PT (n = 275) as initial treatments. A one-to-one propensity score matching (PSM) analysis was performed to evaluate the overall survival (OS) and progression-free survival (PFS) after dividing patients according to liver function as assessed by the modified albumin-bilirubin (mALBI) grade.The median OS (130 vs. 85 month, p = 0.001) and PFS (47 vs. 30 month, p = 0.004) of HR were also significantly better than that of PT in the PSM cohort with mALBI grade 1/2a (n = 145 per group). Meanwhile, in a PSM cohort with mALBI grade 2b/3 (n = 53 per group), there were no significant differences in median OS and PFS between HR and PT.HR may be preferable as an initial treatment for patients with single HCC without vascular invasion, especially those with preserved liver function. PT can be an acceptable alternative to HR for patients without surgical indication and/or impaired liver function.

Background Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study. Methods Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement. Results Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy. Conclusions Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.

This study aimed to research the post-treatment quality of life (QOL) between radiotherapy (RT)- and operation (OP)-treated early cervical cancer survivors, using separate questionnaires for physicians and patients. We administered an observational questionnaire to patients aged 20–70 years old with Stages IB1–IIB cervical cancer who had undergone RT or OP and without recurrence as outpatients for ≥6 months after treatment. We divided 100 registered patients equally into two treatment groups (n = 50 each). The average age was 53 and 44 years in the RT and OP groups, respectively. The RT group included 34 and 66% Stage I and II patients, respectively, whereas the OP group included 66 and 34% Stage I and II patients, respectively. The OP group included 58% of patients with postoperative RT. Combination chemotherapy was performed in 84 and 48% of patients in the RT and OP groups, respectively. On the physicians’ questionnaire, we observed significant differences in bone marrow suppression (RT) and leg edema (OP). On the patients’ questionnaire, significantly more patients had dysuria and leg edema in the OP group than in the RT group, and severe (Score 4–5) leg edema was significantly higher in the post-operative RT group than in the OP only group. The frequency of sexual intercourse decreased after treatment in both groups. On the patients’ questionnaire, there were no significant differences between the two groups regarding sexual activity. These findings are useful to patients and physicians for shared decision-making in treatment choices. The guidance of everyday life and health information including sexual life after treatment is important.

This study aimed to determine the maximum tolerance dose (MTD) and to estimate the recommended dose (RD) of concomitant S-1 with carbon-ion radiotherapy (RT) for sinonasal squamous cell carcinoma (SCC). Nine patients with sinonasal SCC received carbon-ion RT with escalating doses of S-1 according to phase I methods. Doses of 40, 60 and 80 mg/m2/day were administered twice daily in dose levels 1, 2 and 3, respectively, from days 1 to 14 and 22 to 35. Carbon-ion RT was administered at a dose of 70.4 Gy (relative biological effectiveness) in 32 fractions, 5 days a week. Two patients developed grade 3 acute dermatitis. However, none developed dose-limiting toxicities. Therefore, the MTD of S-1 could not be determined; the RD was estimated to be 80 mg/m2/day with concurrent carbon-ion RT. Partial response and stable disease were noted in 5 and 4 patients, respectively. The 2-year overall survival and local control rates were 56 and 74%, respectively. Overall, 2 patients developed ≥grade 3 late toxicities; among them, 1 patient developed grade 3 cataract and the other developed grade 4 cataract, optic nerve disorder and hearing impairment. To the best of our knowledge, this phase I study is the first clinical trial to evaluate concomitant S-1 with carbon-ion RT for sinonasal SCC. The MTD of S-1 could not be determined, and the RD was estimated to be 80 mg/m2/day. This study demonstrated a manageable safety profile for this combination. The observed outcomes may facilitate further evaluation of this novel therapy.

Purpose To investigate the efficacy and safety of proton beam therapy (PBT) for the treatment of stage I non-small cell lung cancer (NSCLC). Methods and Materials Six hundred sixty-nine patients with 682 tumors histologically or clinically diagnosed stage I NSCLC according to the seventh edition of Union for International Cancer Control who received passive-scattering PBT from April 2004 and December 2013 in Japan were retrospectively reviewed to analyze survival, local control, and toxicities. Results Of 669 patients, 486 (72.6%) were men, with a median age of 76 years (range, 42-94 years). NSCLC was histologically confirmed in 440 patients (65.7%). Clinical T stages included T1a (n = 265; 38.9%), T1b (n = 216; 31.7%), and T2a (n = 201; 29.4%). The total irradiation doses of PBT ranged from 74.4 to 131.3 biological effective dose GyE (median, 109.6 biological effective dose GyE). The median follow-up period was 38.2 months (range, 0.6-154.5 months) for all patients. The 3-year overall survival and progression-free survival rates for all patients were 79.5% and 64.1%, respectively. For patients with stage IA tumors, the 3-year overall survival and progression-free survival rates were 82.8% and 70.6%, respectively, and the corresponding rates for patients with stage IB tumors were 70.8% and 47.3%, respectively. The 3-year local progression-free rates for all, stage IA, and stage IB patients were 89.8%, 93.5%, and 79.4%, respectively. The incidence of grade 2, 3, 4, and 5 pneumonitis was 9.8%, 1.0%, 0%, and 0.7%, respectively. The incidence of grade ≥3 dermatitis was 0.4%. No grade 4 or severe adverse events, other than pneumonitis, were observed. Conclusions PBT appears to yield acceptable survival rates, with a low rate of toxicities.

Background: The outcomes of chemotherapy for patients with perihilar cholangiocarcinoma (PHC) are unsatisfactory, and photon therapy for unresectable PHC reportedly results in improved outcomes. Proton beam therapy (PBT) can be a treatment option for these patients; however, the role of PBT in these patients is poorly defined as PHC is rare. Herein, we evaluated the efficacy and safety of PBT for unresectable PHC.Methods: This observational retrospective cohort study conducted at a single institution included patients with unresectable PHC who received definitive PBT. Patients who had nodal metastasis at presentation or those who underwent surgery or other radiation therapies before PBT were excluded. To compare different dose fractionations, biologically equivalent doses with α/β=10 [BED10] were calculated.Results: Overall, 26 patients were eligible. The commonly prescribed doses were 67.5 Gy (relative biological effectiveness [RBE]) in 25 fractions or 70.2 Gy (RBE) in 26 fractions. The median follow-up period was 19.4 months (range, 4.2-137.4 months). The Kaplan–Meier estimates of the 1-, 2-, and 5-year overall survival (OS) rates were 72.9%, 47.7%, and 17.4%, respectively, and the median survival time was 23.7 months. The multivariate analysis demonstrated that Child–Pugh classification B was a significant prognostic factor for unfavorable OS (hazard ratio [HR] 4.92; p=0.009) and that a mean gross tumor volume dose of ≥79.2 Gy (RBE) [BED10] was a significant prognostic factor for favorable OS (HR 0.19; p=0.025). Grade ≥3 late adverse events were observed in seven patients (26.9%).Conclusions: We demonstrated that definitive PBT for patients with unresectable PHC might improve the prognosis. Further large-scale prospective studies are warranted to validate our findings.

Background Factors associated with long-term survival in gemcitabine-concurrent proton radiotherapy (GPT) for non-metastatic, locally advanced pancreatic cancer (LAPC) remain unclear. This study aimed to determine the factors associated with long-term survival in GPT for non-metastatic LAPC. Methods The medical records of 123 patients with LAPC treated with GPT between February 2009 and December 2019 at Hyogo Ion Beam Medical Center were retrospectively reviewed to assess the factors associated with long-term survival outcomes. Results The median overall survival of the total cohort treated with GPT was 18.7 months. The 1- and 2-year overall, local progression-free, and progression-free survival rates were 70.4% and 35.7%, 78.2% and 59.0%, and 38.6% and 20.8%, respectively. Multivariate analysis revealed that LAPCs at the pancreatic body-tail and those without anterior peripancreatic invasion were independently associated with longer overall survival (P = 0.040 and P = 0.015, respectively). The median overall survival of patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion were 24.1 and 28.1 months, respectively. LAPCs at the pancreatic body-tail had a higher volume ratio irradiated over 60 Gy equivalents at gross tumor volume than those at the pancreatic head (P P = 0.039). Conclusions GPT is a promising treatment option for patients with LAPC at the pancreatic body-tail and those with LAPC without anterior peripancreatic invasion.

There are currently no reliable, established serum biomarkers to predict the prognosis of radiotherapy for advanced cervical cancer. We aimed to identify serum biomarkers for survival after radiotherapy for cervical cancer. In this multicenter prospective cohort study, the usefulness of pre- and posttreatment serum protein levels of potential biomarkers, including squamous cell carcinoma antigen (SCC-Ag), apolipoprotein C-II (ApoC-II), matrix metalloproteinase (MMP)1, and MMP2, were evaluated together with clinical factors in 145 cervical cancer patients in order to determine their suitability to predict survival. Progression-free survival (PFS) was the primary endpoint, and overall survival (OS), pelvic PFS (PPFS), and distant metastasis-free survival (DMFS) were the secondary endpoints. Blood samples were collected before and 1 month after radiotherapy to measure serum biomarker levels. ApoC-II was measured using a monoclonal antibody-based enzyme-linked immunosorbent assay, which was developed for this purpose. Kaplan-Meier method, log-rank test, and univariate and multivariate Cox proportional hazards models were used for statistical analyses. In multivariate analysis, larger tumor size was independently associated with shorter PFS, OS, PPFS, and DMFS, while longer overall treatment time was independently associated with shorter PPFS. Higher pretreatment SCC-Ag (P < 0.001) was associated with shorter DMFS. Higher posttreatment SCC-Ag (P = 0.017) was also associated with shorter DMFS. Pretreatment ApoC-II was associated with PPFS in univariate analysis (P = 0.048), but not in multivariate analysis. Patients with pretreatment ApoC-II levels ≤ 25.8 μg/ml had shorter PPFS than those with pretreatment ApoC-II levels > 25.8 μg/ml (P = 0.023, log-rank test). Pre- and posttreatment serum SCC-Ag and pretreatment serum ApoC-II levels may be important biomarkers to predict survival outcomes of patients with cervical cancer after radiotherapy. Pre- and posttreatment SCC-Ag and pretreatment ApoC-II might be useful in clinical settings for screening patients to improve treatment strategies in cervical cancer.

Purpose Although proton therapy is controversial, it has been used to treat localized prostate cancer over the past 2 decades. The purpose of this study is to examine the long-term efficacy and toxicity of proton therapy for localized prostate cancer. Methods and Materials This was a retrospective observational study of 2021 patients from 2003 to 2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and 6% of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated using the Kaplan-Meier method and were analyzed using multivariable Cox proportional hazards models. Results The median follow-up period was 84 months (interquartile range, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100% and 100%, 99% and 88%, 93% and 86%, 90% and 79%, 88% and 68%, and 76% and 63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high-risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. The results of multivariable analyses indicate that younger patients more often experienced biochemical relapse. Conclusions This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that accounts for the patient’s age.

Purpose This retrospective study aimed to determine the clinical outcomes following particle monotherapy (ie, proton therapy [PT] or carbon ion therapy [CIT]) in patients with sinonasal squamous cell carcinoma at a single institution. Methods and Materials Between August 2001 and March 2012, 59 patients were treated with definitive PT or CIT; none underwent chemotherapy or surgery. Of the patients, 22 (37%) had unresectable disease. PT was used in 38 patients (64%); CIT, 21 patients (36%). Almost half of the patients (n = 29, 47%) received 65.0 Gy (relative biological effectiveness) in 26 fractions. Results The median follow-up period was 30 months (range, 8-127 months) for all patients and 65 months (range, 9-127 months) for the survivors. The 3- and 5-year overall survival rates were 56.2% and 41.6%, respectively; progression-free survival rates, 42.9% and 34.7%, respectively; and local control rates, 54.0% and 50.4%, respectively. Late toxicities of grade ≥3 occurred in 13 patients (22%). Conclusions To our knowledge, this is the largest retrospective study of sinonasal squamous cell carcinoma treated with particle therapy alone. The efficacy of PT and CIT indicated that particle therapy can serve an important role in treating this disease.

Purpose To evaluate the efficacy and safety of definitive proton beam therapy (PBT) for primary sacral chordoma. Methods and Materials We conducted a retrospective analysis of the clinical outcomes of eligible patients with primary sacral chordoma who had undergone definitive PBT with 70.4 Gy (relative biological effectiveness) in 32 fractions at our institution from September 2009 to October 2015. Local progression-free survival, distant metastasis-free survival, disease-free survival, cause-specific survival, and overall survival were evaluated. To explore the factors that influenced local progression, the following parameters were analyzed: sex, the presence of a spacer (Gore-Tex sheets), gross tumor volume, and extent of cranial tumor extension. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. To assess the impact of PBT on pain relief, the change in pain grades was investigated between the initiation of PBT and the last follow-up visit. Results Thirty-three eligible patients were analyzed. The median follow-up period was 37 months. The 3-year estimated local progression-free survival, distant metastasis-free survival, disease-free survival, cause-specific survival, and overall survival rates were 89.6%, 88.2%, 81.9%, 95.7%, and 92.7%, respectively. No significant association was between the patients’ clinicopathologic characteristics and local progression-free survival. Four patients developed grade 3 adverse events, including acute dermatitis (n = 1), ileus (n = 1), and pain due to sacral insufficiency fractures (n = 2). The pain grades had improved, were unchanged, or had deteriorated in 15, 7, and 11 patients, respectively. Conclusions Definitive PBT with 70.4 Gy (relative biological effectiveness) in 32 fractions is an effective treatment with acceptable toxicity for primary sacral chordoma and has the potential to reduce pain.

Our aim was to assess the patterns of practice and treatment outcomes of definitive radiotherapy (RT) for vaginal cancer in Japan. RT methods and outcomes of patients with vaginal cancer treated with definitive RT or chemoradiotherapy at 10 institutes of the Japanese Radiation Oncology Study Group between January 2000 and March 2010 were retrospectively evaluated. A total of 90 patients were enrolled in the study. The clinical stages were I, II, III, and IVA in 34, 36, 16, and 4 patients, respectively. Seventy patients were treated with three-dimensional conformal RT (3DCRT) and brachytherapy (BT), 12 with BT alone, and 8 with 3DCRT alone. Chemotherapy was administered to 29 patients. The 5-year overall survival and local control rates were 77 and 83% with a median follow-up period of 94 months for surviving or lost patients. The 5-year overall survival rates according to stage were 94, 71, 56, and 75% for stages I, II, III, and IVA, respectively. The 5-year local control rates according to stage were 94, 77, 74, and 75% for stages I, II, III, and IVA, respectively. Twenty-nine percent (6 of 21 patients) of local recurrences occurred between 5 and 10 years after RT. The 10-year local control rate of all patients was 71%. Significant prognostic factors for overall survival by univariate and multi-variate analyses were performance status, tumor size, and pelvic lymph node metastasis. Grade 3 late radiation morbidity of the rectum, pelvic bone, urinary bladder, and skin developed in 9% (8 of 90 patients). Good outcomes similar to those of cervical cancer can be achieved with definitive RT delivered by 3DCRT and/or BT for vaginal cancer. Long follow-up is necessary for a continuing risk of local recurrence after 5 years.

Background The primary definitive treatment for abdominopelvic sarcomas (APSs) is resection, although incomplete resection has a negative prognostic impact. Although the effectiveness of particle therapy (PT) as a treatment for APS has already been demonstrated, its application for tumors adjacent to the gastrointestinal tract is frequently restricted, due to extremely low tolerance. Space-making PT, consisting of surgical spacer placement and subsequent PT, has been developed to overcome this limitation. Materials and methods Between June 2006 and June 2018, a total of 75 patients with 12 types of APS underwent space-making PT. Results The 3-year local control rate of all patients was 90.3%. Fourteen surgery-related complications were observed in 12 patients (16%), and complications of Grade 3b or higher were observed in 3 patients. Ninety-five PT-related complications were seen in 66 patients (88.0%), and 13 patients (17.3%) had complications of Grade 3 or higher. The median V95% (volume irradiated with 95% of the treatment planning dose) of the gross tumor volume and clinical target volume were 99.9% and 99.5%, respectively. The median D95% (dose intensity covering 95% of the target volume) of the gross tumor volume/planned dose and clinical target volume/planned dose were 99.4%, and 99.1%, respectively. Conclusion The feasibility and effectiveness of space-making PT have been demonstrated via dosimetric evaluation, and our results indicate that this new strategy may potentially provide an effective and innovative treatment option for advanced APS.

OBJECTIVE To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy. METHODS A retrospective chart review was performed. RESULTS Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25-115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of

The optimal treatment for isolated local recurrence (ILR) of pancreatic adenocarcinoma (PDAC) after surgical resection remains unclear. This study aimed to evaluate the safety and efficacy of proton radiotherapy (PRT) for ILR of PDAC after surgery. The medical records of patients with ILR of PDAC after surgery who underwent proton beam therapy between 2011 and 2015 at Hyogo Ion Beam Medical Center were retrospectively studied. The study analyzed 30 patients (14 women and 16 men) with a median age of 65 years (range 38–81 years) who had initially undergone pancreatoduodenectomy (n = 23) or distal pancreatectomy (n = 7) for their primary tumors. Upon ILR, PRT was administered with a median total cumulative dose of 67.5 gray equivalent (GyE) (range 50–67.5 GyE) using 19 to 25 fractions. For 25 patients, concurrent chemotherapy was administered using gemcitabine (n = 18) or S-1 (n = 7). Four patients (13.3%) experienced acute grade ≥ 3 gastrointestinal toxicities. After a median follow-up period of 17.6 months (range 2.1–50.4 months), 23 patients had experienced tumor progression and 10 had died. Nine patients (30%) experienced local tumor progression. The median overall, progression-free, and local progression-free survival rates were 26.1, 12.3, and 41.2 months, respectively. Pre-PRT serum levels of cancer antigen 19-9 higher than 100 U/mL and duke pancreatic monoclonal antigen type 2 higher than 150 U/mL were significantly associated with shorter progression-free survival rates. Proton radiotherapy for ILR of PDAC after surgery is well tolerated and produces good locoregional control and should be considered for eligible patients.

There are few reports about the clinical results of proton beam therapy for esophageal cancer in a large population. The purpose of this study was to evaluate the clinical results of proton beam therapy for esophageal cancer in a large population using a multicentered database. Between January 2009 and December 2013, patients newly diagnosed with esophageal cancer and who had received proton beam therapy were retrospectively recruited from a database of four proton beam therapy centers in Japan. Two hundred and two patients (including 90 inoperable patients) fulfilled the inclusion criteria, and 100 patients (49.5%) had stage III/IV cancer (Union for International Cancer Control 8th). The 3-year and 5-year overall survival rate was 66.7% and 56.3%, respectively. The five-year local control rate was 64.4%. There were two patients with grade three pericardial effusion (1%) and a patient with grade three pneumonia (0.5%). No grade 4 or higher cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events version 4.0). This study suggests that proton beam therapy for esophageal cancer was not inferior in efficacy and had lower rates of toxicities in comparison to photon radiotherapy. Therefore, proton beam therapy can serve as an alternate treatment for patients with esophageal cancer.

Purpose To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm 3 (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm 3 were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm 3 were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P Conclusions Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a longer follow-up period is needed to confirm these results.

Our purpose was to develop recommendations for contouring the computed tomography (CT)-based high-risk clinical target volume (CTVHR) for 3D image-guided brachytherapy (3D-IGBT) for cervical cancer. A 15-member Japanese Radiation Oncology Study Group (JROSG) committee with expertise in gynecological radiation oncology initiated guideline development for CT-based CTVHR (based on a comprehensive literature review as well as clinical experience) in July 2014. Extensive discussions occurred during four face-to-face meetings and frequent email communication until a consensus was reached. The CT-based CTVHR boundaries were defined by each anatomical plane (cranial–caudal, lateral, or anterior–posterior) with or without tumor progression beyond the uterine cervix at diagnosis. Since the availability of magnetic resonance imaging (MRI) with applicator insertion for 3D planning is currently limited, T2-weighted MRI obtained at diagnosis and just before brachytherapy without applicator insertion was used as a reference for accurately estimating the tumor size and topography. Furthermore, utilizing information from clinical examinations performed both at diagnosis and brachytherapy is strongly recommended. In conclusion, these recommendations will serve as a brachytherapy protocol to be used at institutions with limited availability of MRI for 3D treatment planning.

To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study.Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy(10) (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review.Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6-39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7-72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%-100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%-98%) and 95% (95% CI, 89%-100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥ 1) were 18% (95% CI, 8%-28%) for large intestine/rectum, 4% (95% CI, 0%-8%) for small intestine, and 0% for bladder. No Grade ≥ 3 cases were observed for genitourinary/gastrointestinal late complications.These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy(10) at point A) can provide excellent local control without severe toxicity in nonbulky (4-cm) early-stage cervical cancer.

当科では下咽頭癌に対し初治療として化学放射線同時併用療法（chemoradiotherapy；CRT）を行い，CRT 40Gyによる原発巣奏効度がCR（またはほとんどCR）であれば根治的CRTを施行し，PRまでであれば根治切除術に移行するという集学的治療を行ってきた。今回，2000年から2007年の間にこの方針にて治療を行った下咽頭癌症例の治療成績を，生存率と喉頭保存率について検討した。CRTはすべて低容量抗癌剤の併用（低容量CRT）であり，CRT 40Gyで原発巣がCRとなった症例はT1 or 2N0群12例中10例（83%），T1 or 2N1-3群15例中10例（67%），T3 or 4N0-3群22例中7例（32%）であった。各群の疾患特異的5年生存率と喉頭保存率は，それぞれT1 or 2N0群；81%と67%，T1 or 2N1-3群；47%と67%，T3 or 4N0-3群；49%と27%であった。T1 or 2N0-3症例では低容量CRTにより70%程度の喉頭保存率が期待できるが，30%程度の低感受性症例では局所制御のために原発巣切除術や高容量抗癌剤を併用するCRT（高容量CRT）が必要と思われた。また，T1 or 2N1-3症例の生存率向上のためには高容量CRTや頸部郭清術を適切に組み込む必要があると思われた。T3 or 4N0-3症例では根治切除術の必要性が大きいが，30%程度の高感受性症例では低容量CRTでも喉頭保存が期待でき，この群の喉頭保存率をさらに高めるためには高容量CRTや動注CRTなどの強力なCRTが必要と思われた。CRT 40Gyでの原発巣奏効度に基づき治療法を決める集学的治療は，CRTに対する感受性に応じて治療法を選択する治療体系であり，下咽頭癌の根治や喉頭保存を図る有用な方法の一つである。

We have conducted nationwide surveys of primary central nervous system lymphoma (PCNSL) treated since 1985. In the present study, we newly collected data between 2000 and 2004 and investigated changes in clinical features and outcome over time. A total of 739 patients with histologically proven PCNSL under going radiotherapy were analyzed. Seventeen institutions were surveyed, and data on 131 patients were collected. These data were compared with updated data that were previously obtained for 466 patients treated during 1985-1994 and 142 patients treated during 1995-1999. Recent trends toward decrease in male/female ratio, increase in aged patients, and increase in patients with multiple lesions were seen. Regarding treatment, decrease in attempts at surgical tumor removal and increases in use of systemic chemotherapy and methotrexate (MTX)-containing regimens were observed. The median survival time was 18, 29, and 24 months for patients seen during 1985-1994, 1995-1999, and 2000-2004, respectively, and the respective 5-year survival rates were 15%, 30%, and 30%. In groups seen during 1995-1999 and during 2000-2004, patients who received systemic or MTX-containing chemotherapy had better prognosis than those who did not. Multivariate analysis of all patients seen during 1985-2004 suggested the usefulness of MTX-containing chemotherapy as well as the importance of age, lactate dehydrogenase level, and tumor multiplicity as prognostic factors. Thus, this study revealed several notable changes in clinical features of PCNSL patients. The prognosis improved during the last 10 years. Advantage of radiation plus chemotherapy, especially MTX-containing chemotherapy, over radiation alone was suggested.

Objective. In most cases of uterine cervical carcinoma recurrence, the first site of distant metastasis or recurrence is reported to be the para-aortic region. Some reports have demonstrated that, in cases of isolated para-aortic lymph node recurrence treated by radiation therapy, patients survived for a long period, which suggests that isolated para-aortic lymph node recurrence in uterine cervical carcinoma is a regional disease rather than systemic disease. Determining the predictive characteristics of isolated para-aortic lymph node recurrence in patients at the time of the initial treatment for primary uterine cervical carcinoma is important, so we conducted the current multi-institutional study. Patients and methods. Patients ( n =3137) with uterine cervical carcinoma of stages Ia to IVa were treated in twelve Japanese hospitals between 1994 and 2003. The current study investigated the frequency and characteristics of patients with isolated para-aortic lymph node recurrence as well as the characteristics of clinical stage, histopathology, serum squamous cell carcinoma antigen level, the treatment method at the initial treatment, the duration between the initial treatment and the recurrence, and the serum squamous cell carcinoma antigen level at the recurrence. Results. Of the 3137 patients with uterine cervical carcinoma in stages Ia–IVa, 67 (2.1%) experienced recurrence in isolated para-aortic lymph nodes. Stratified by clinical stage, none of the 613 patients with stage Ia experienced recurrence in isolated para-aortic lymph nodes. However, recurrence was experienced by 14 (1.4%) of the 966 patients with stage Ib, 7 (3.5%) of the 199 patients with stage IIa, 14 (2.3%) of the 613 patients with stage IIb, 1 (2.1%) of the 48 patients with stage IIIa, 26 (4.6%) of the 538 patients with stage IIIb, and 5 (5%) of the 100 patients with stage IVa. The mean duration time between the initial treatment and isolated para-aortic recurrence was 20 months (range, 2–49 months). The correlations between duration time and the clinico-pathological factors (clinical stage, histopathology, serum squamous cell carcinoma antigen level, and treatment method) at the initial treatment were investigated. No statistically significant factors have been revealed in the current study. Conclusions. The frequency of isolated para-aortic lymph node recurrence was 2.1% and increased with increasing clinical stage at the initial treatment (stage IVa: 5%) in the current study.

This study evaluated the clinical features and treatment outcome of 15 patients with primary intraocular lymphoma. There were nine females, with a median age of 68 years. Thirteen patients presented with bilateral lesions and median time from the onset of symptoms to diagnosis was 12 months. All but one showed the B-cell phenotype. All patients received radiation therapy (RT) with a median of 41 Gy and 10 were administered chemotherapy as well. Three patients were treated with high-dose methotrexate and nine received prophylactic cranial irradiation (PCI) with a median of 30.6 Gy. Thirteen patients obtained a complete remission. The 2-year overall and disease free survival were 74% and 58%, respectively. Although only one patient experienced local recurrence, PCI did not prevent intracranial recurrence. One patient developed a grade 3 cognitive disturbance. It was concluded that ocular RT was effective to control primary lesions. However, some modifications are indispensable to improve outcomes.

Objective To retrospectively analyze the clinical outcomes of radiation therapy with or without chemotherapy for bladder cancer in Japan. Methods A questionnaire-based survey of patients with pathologically proven bladder cancer treated by definitive radiation therapy between 2002 and 2006 was conducted by the Japanese Radiation Oncology Study Group, and the clinical records of 159 patients were collected from 17 institutions. Concurrent intra-arterial chemoradiotherapy and concurrent systemic chemoradiotherapy were administered in 51 and 33 patients, respectively. Results The 5-year overall survival and bladder preservation rates were 48 and 39%, respectively. Eighty-nine (56%) patients developed recurrence (bladder, 48; regional lymph nodes, 4; distant sites, 41). The results of multivariate analysis revealed that adoption of chemotherapy was the only significant prognostic factor for overall survival (relative risk = 0.615 [95% confidence interval: 0.439-0.862], P = 0.005). The type of chemotherapy administered did not significantly affect the local control or overall survival rates. The actuarial 5-year overall survival rates and bladder preservation in the radiation therapy combined with intra-arterial chemotherapy group were 64 and 58%, respectively, and the corresponding rates in the radiation therapy combined with systemic chemotherapy group were 67 and 42%, respectively. Conclusions The results of this survey revealed the current status of practice of radiation therapy for bladder cancer in Japan. A multi-institutional prospective study is needed based on the results of this study to determine the optimal radiotherapeutic approach, including the need for concurrent chemotherapy and the appropriate chemotherapy regimen for invasive bladder cancer.

The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995–2004 and those on 466 patients treated during the period 1985–1994. In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005–2009 period compared to the 1985–2004 period (63 vs. 58–59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005–2009 period compared with the 1995–2004 period (World Health Organization PS 0–2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995–2004 period, significant changes in the 2005–2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985–1994, 1995–2004, and 2005–2009 periods, respectively, but relapse-free survival did not improve between the 1995–2004 and 2005–2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.

To seek for the possible factors influencing overall survival (OS) with radiotherapy (RT) for biliary tract cancer.Data were collected retrospectively from RT database of 31 institutions in Japan. All patients underwent at least external beam RT. The factors influencing OS were investigated.Data of 498 patients were analyzed. Median OS of the 212 patients who underwent surgery was significantly better than that of the 286 patients without surgery (31 vs. 15 months, p0.001). The OS for the R0 or R1 resection group was significantly longer than that for the R2 or non-surgery group, as well as for n0 compared to n1 (all p0.001). Chemoradiotherapy (CRT), both sequential and concurrent, resulted in a better OS than RT alone for the n1 group (31 vs. 13 months, p0.001), and marginally better for the R0/R1 group (p=0.065; p=0.054 for concurrent CRT). However, no such benefit was observed for the R2/non-surgical patients. Multivariate analysis identified performance status, clinical stage, and surgery as significant factors.Surgery, especially R0/R1 resection, seemed as the gold standard for treatment of biliary tract cancer including RT, even in the highly heterogeneous population obtained from the multicenter retrospective study. The possibility was shown that CRT yielded better survival benefit especially for n1 patients. We recommend that future prospective trials include an arm of adjuvant CRT at least for n1 and possibly R0/R1 patients.

To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG).Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients.The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels.The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

Adverse events and therapeutic effects were analyzed in patients with pharyngeal or advanced laryngeal squamous cell carcinomas(SCCs)receiving concurrent chemoradiotherapy (CCRT) with S-1 or weekly CDDP between 2004 and 2007. Low-dose CDDP (25 mg/m2) was administered once a week and S-1 (65 mg/m2) was administered for 3 weeks with one-week rest during conventional radiation with 2 Gy/fraction. Both of the two CCRT regimens showed little toxicity with grade 4 toxicities in less than 5%of the patients. However, CCRT with S-1 more frequently induced grade 3 and 4 oral mucositis than CCRT with CDDP. As a result, the completion rate of CCRT with S-1 was lower than that of CCRT with CDDP. The two regimens achieved a similar complete response rate of the primary sites, local control rate(LCR)and larynx preservation rate; the LCR for T1 and 2 disease was more than 70%. However, the LCR for T3 or 4 disease by the two regimens was less than 50%. CCRT with S-1 showed significantly higher LCR in patients with poorly or undifferentiated SCCs than those with well or moderately-differentiated SCCs. It is suggested that the two CCRT regimens are useful treatment modalities for patients with locally(primary site)non-advanced pharyngeal or laryngeal SCCs, and that CCRT with S-1 is highly sensitive to poorly or undifferentiated SCCs. In order to achieve local control and larynx preservation, more intensive CCRT might be necessary for patients with locally(primary site)advanced pharyngeal or laryngeal SCCs.

To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma.The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months).At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater.Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.

Background: We investigated the interobserver variation in the prostate target volume and the trend toward the use of diagnostic computed tomography (CT) or magnetic resonance (MR) images for treatment planning. Methods: Twenty-five radiation oncologists were asked to draw the external contour of the prostate on CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also answered a questionnaire regarding the use of diagnostic CT or MR images for the contouring. Results: Of the 25 physicians, 28% rarely or never referred to the diagnostic CT images. In contrast, the physicians tended to refer to the MR images more frequently. Approximately 50% of the physicians believed in the usefulness of contrast-enhanced images for the delineation of the prostate. As for the variation of the prostate contouring, the median craniocaudal prostate length was 36 mm (range, 21 –5 4 mm), and the median prostate volume was 43.5 cm 3 (range, 23.8–98.3 cm 3 ). The interobserver variability was not significant in the duration as a radiation oncologist, the board certification status as radiation oncologists, and the number of treatment plans developed for prostate cancer during the last 1 year. Conclusion: A wide variety of the definitions of the prostate was found among Japanese radiation oncologists.

Purpose: Most patients who had any recurrent sites of cancer have been considered to be in their last stage of life. However, recent advances of clinical research reveal some patients achieve long-term survival even in recurrence. Furthermore, for patients who had only one recurrent region, radiation therapy could play an important role. As for uterine cervical carcinoma, the most common recurrent site other than the pelvis is the para-aortic lymph nodes. Thus we conducted the current study. Patients and Methods: Between 1994 and 2003, more than 5,000 uterine cervical carcinoma patients were treated with curative intended treatments at 13 Japanese hospitals. Of these patients, 84 developed para-aortic lymph node recurrence as the only site of initial tumor progression. These patients were treated with external beam radiation therapy. Radiation therapy protocol was as follows: 1.7–2.0 Gy per fraction, 5 fractions per week, and the mean total dose was 50.8 Gy (25–60 Gy). Results: Three- and 5-year overall survival rates of all patients were 49.5% and 31.3%, respectively. Stratified by symptom sign, 3-year overall survival rate of symptom positive was 27.6% and those of the negative was 56.1% ( p = 0.018). Three-year overall survival rates of the total dose ≥51 Gy and that of ≤50 Gy were 58.0% and 42.8%, respectively ( p = 0.07). As for morbidity, no patients received Grade 3 or greater late toxicity. Conclusions: The current study suggested that radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma could have a significant impact on survival.

Medulloblastomas are highly lethal tumors when they recur. Very few patients survive with conventional treatment. This report documents the preliminary study results of a treatment for recurrent medulloblastomas consisting of stereotactic radiation therapy (SRT) with chemotherapy. Four patients had local recurrence without apparent metastases and 8 patients had metastases with or without local recurrence. Twelve patients with 18 lesions underwent SRT as a single session (n = 8) or in a hypofractionated manner (n = 10) using a gamma knife or modified linear accelerator. All patients then received systemic chemotherapy. Five patients were treated with one to two sequential courses of high-dose chemotherapy with peripheral blood stem cell transplantation. The reduction in tumor size after SRT was often remarkable. Fourteen of 18 lesions treated disappeared 1–6 months after SRT. Two of 4 patients who had local recurrences without apparent metastasis at the time of SRT are alive without evidence of disease 70 and 72 months after SRT, respectively. In contrast, all 8 patients with metastasis had new lesions either in the spinal canal or on the surface of the brain outside the target area of SRT. Median progression-free survival and overall survival from the time of SRT were 9 and 19 months, respectively. The Kaplan-Meier estimates of PFS and overall survival at 3 years were 17 and 25%, respectively. One patient had brainstem edema after SRT causing bulbar palsy and quadriparesis. One patient died of toxicity of chemotherapy. Our experience suggests that local recurrence can be controlled by SRT with chemotherapy but survival of patients with metastases can not be improved effectively by SRT in conjunction with aggressive chemotherapy.