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Purpose: This study aimed to analyze treatment outcomes and prognostic markers, including immune and inflammatory factors, of postoperative radiation therapy (RT) administered to patients with cholangiocarcinoma (CCA).Methods: We retrospectively selected 59 patients with CCA who underwent surgery and postoperative RT with curative intent from 2004 to 2019. Patients received external irradiation (50 Gy in 25 fractions) using three-dimensional RT. Overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS), and locoregional control (LRC) rates of initial RT were assessed using the Kaplan–Meier method. Univariate and multivariate Cox proportional-hazards regression models were used to identify prognostic factors. We analyzed prognostic factors of inflammation, such as pre-RT platelet count, hemoglobin, lymphocyte count ratio (LCR) of the leukocyte count, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR).Results: Tumor stages were distributed as follows: I (n = 8), II (n = 25), III (n = 15), and IVA (n = 11). The median follow-up was 24 months. Two-year OS, CSS, PFS, and LRC rates were 59.5%, 62.0%, 40.1%, and 66.7%, respectively. Univariate analysis revealed that lower LCR was significantly associated with shorter PFS (P = 0.0446, hazard ratio (HR): 1.90, 95%, confidence interval (CI): 1.02–3.58). There was no significant difference between the median baseline values of PLR and NLR; and age ≥75, positive regional lymph node metastases (N+), and chemotherapy after RT were significantly associated with poor OS. Multivariate analysis revealed a significant association of N+ with OS, PFS and CSS and that lower LCR was significantly associated with PFS (HR: 0.481, CI: 0.252–0.905, p=0.0234). Among late toxicity events, two patients (3.38%) were suspected with therapy-related liver toxicity.Conclusions: LCR before RT was a prognostic factor for postoperative radiation therapy of patients with CCA.

Background/Aim: To evaluate the preventive effects of regional lymph node irradiation on lymph node recurrence in esophageal cancer (EC). Patients and Methods: The study included 289 patients who received definitive radiotherapy for EC. The regional lymph node area of group 1 was determined as the area with the highest probability of lymph node metastasis and group 2 was determined as the area with the next highest probability of lymph node metastasis depending on the primary site of EC. Results: The patients in whom group 2 was completely included in the irradiated field had a significantly lower rate of recurrence of regional lymph node metastasis than those in whom group 2 was not or insufficiently included (p=0.0337). There was no significant difference in overall survival (p=0.4627) or disease-specific survival (p=0.6174) between the two groups. Conclusion: Regional lymph node irradiation did not have survival-prolonging effects but significantly reduced regional lymph node recurrence.

Purpose Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. Methods Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. Results Six Japanese patients (three men and three women; mean age 61.5 years; range 50–70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%–69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0–21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2–21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. Conclusion PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

Highlights • Proton beam therapy is likely to be safe for liver hemangiomas because, in our experience. • Proton beam therapy achieves good local control for liver hemangiomas without causing severe hepatic damage. • Proton beam therapy expected to minimize the risk of late adverse events., Background Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. Case presentation A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. Conclusion This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.

Background/Aim: We examined the difference between whole-brain radiation therapy (WBRT) for intracranial metastases (IM) from lung cancer as an initial and as a late treatment affecting overall survival (OS). Patients and Methods: Thirty-three patients who presented with IM at initial examination who received WBRT as the initial treatment (initial WBRT group) and 47 patients without IM or with asymptomatic IM at initial examination who received WBRT after systemic therapy, between January 2014 and December 2020, were retrospectively analyzed. Patients’ OS after WBRT were compared. Results: Median OS was significantly longer in patients treated with systemic anticancer therapy after WBRT than in patients who were not (176 vs. 47 days, respectively; p

Background Radiotherapy is often used for treating patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas who fail to respond to Helicobacter pylori eradication. However, non-gastric intestinal MALT lymphoma is rare, and no standard therapeutic strategies have been established. This study was designed to assess the long-term prognosis of non-gastric intestinal MALT lymphoma treated with radiotherapy and to compare the outcomes with that of post-radiotherapy gastric MALT lymphoma. Methods The study included 34 patients with stage I EA gastrointestinal MALT lymphoma according to the Ann Arbor classification who underwent definitive radiotherapy. The primary site was the rectum in 3, the duodenum in 1, and the stomach in 30 patients. The radiotherapy dose was 1.5?2.0 Gy (median, 1.5 Gy) and the total dose was 30?40 Gy (median, 30 Gy). The clinical target volume (CTV) was defined as the volume of the entire organ with the lymphoma. Adjacent lymph node areas were not routinely included in the CTV. Results Complete response (CR) was achieved in all patients. There were no local recurrences, and two cases of recurrence were observed at other sites. The 5-year overall survival rates for non-gastric and gastric MALT lymphomas were 100% and 94.7%, respectively, and the 5-year disease-free survival rates were 100% and 95.7%, respectively. None of the patients died of the current illness. Conclusion Radiotherapy for non-gastric intestinal MALT lymphoma is expected to result in good local control and long-term survival, similar to that for gastric MALT lymphoma.

Background/aim This study aimed to evaluate the effect of intensity-modulated radiation therapy (IMRT) on the clinical outcomes of patients with lymph node (LN) oligo-recurrence and a controlled primary tumor. Patients and methods We retrospectively reviewed the medical records of 21 patients diagnosed with LN oligo-recurrence who received IMRT with curative intent. Patients with tumor of various primary sites and histopathological types were included in this study. Results The 3-year overall survival (OS) and in-field progression-free survival (PFS) rates were 75% and 52%, respectively. Statistical analysis showed that lower dose to the gross tumor volume (GTV) and larger GTV were significantly associated with poorer OS; adenocarcinoma and lower dose to GTV were significantly associated with poorer in-field PFS. No patients experienced severe adverse events. Conclusion IMRT may provide a safe and effective treatment for patients with LN oligo-recurrence. Tumor dose-escalation sparing normal tissue using IMRT technology may improve the OS and in-field PFS.

Background/aim This study aimed to evaluate the clinical outcome of intensity-modulated radiation therapy (IMRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) in uterine cervical cancer (UCC). IMRT consisted of whole-pelvic radiation therapy (WPRT) and sequential WPRT with central-shielding (WPRT-CS). Patients and methods Thirty UCC patients treated with IMRT using TomoTherapy, were retrospectively analyzed. Results The median dose of WPRT and WPRT-CS was 36 and 14.4 Gy and the median total dose of these was 50 Gy in 25 fractions (Fr). Median HDR-ICBT dose/Fr to Point A was 25 Gy/5 Fr. Median 2 Gy per fraction-equivalent dose (EQD2) of combined WPRT and HDR-ICBT to Point A (α/β=10) was 71.0 Gy. The 3-year local control, disease-free survival, and overall survival rates were 89.9%, 83.3%, and 86.3%. Conclusion IMRT of WPRT and WPRT-CS given in combination with HDR-ICBT was a feasible therapy resulting in good disease control and tolerance in patients with UCC.

Aim Whole‐breast radiation therapy after breast‐conserving surgery can control local recurrence with a long‐term survival rate equivalent to that of radical mastectomy for patients with early breast cancer. However, the significance of radiation therapy for patients with positive/close margins after mastectomy remains controversial. Following radical mastectomy, no residual breast parenchyma remains, and thus radiation therapy of the entire chest wall may represent overtreatment in the patients, especially those without lymph node metastasis (N0). We therefore implemented partial chest wall radiation therapy for patients with N0 breast cancer and positive and/or close margins after mastectomy. Methods A total of 22 patients with N0 status but positive/close margins underwent partial chest wall radiation therapy to irradiate the predetermined clinical target volume, which had margins of at least 2 cm medial, lateral, superior, and inferior to the primary tumor bed. With reference to chest wall thickness, 4‐10‐MV photons or 5‐8‐MeV electrons with/without a bolus were delivered. The total dose was 50‐66 Gy. We compared the results with those from 18 nonradiation therapy patients using Pearson's χ 2 test. Results All patients in the partial chest wall radiation therapy group achieved good local control despite having a significantly higher proportion of positive margins (77.3%) compared with the nonradiation therapy group (27.8%) (P = 0.002). Both groups showed 100% recurrence‐ and disease‐free survival. Conclusion Partial chest wall radiation therapy may offer recurrence‐ and disease‐free survival without local recurrence in N0 mastectomy patients with positive/close surgical margins.

Preoperative whole pelvic radiation therapy (RT) is used commonly for rectal cancer and is the standard field postoperatively in gynecological cancer. However, the ideal field (local vs. whole pelvis) has not been determined for local recurrence of these cancers.We retrospectively reviewed the data for 52 patients who developed local tumor recurrence of rectal or gynecological cancer treated from 2013 to 2021. The initial treatment for all patients was total excision of the primary tumors without radiation therapy. Radiation therapy targets were surgical stumps, perianastomosis sites, and pelvic lymph nodes, classified according to the pelvic nodal volume atlas for radiation therapy. Patients were divided into the local recurrent tumor only radiation therapy group and the whole pelvis radiation therapy group. Whole pelvis radiation therapy included the common iliac lymph nodes or prophylactic lymph nodes below the L5/S1 junction. We recorded second recurrence after RT and the affected site(s) in each group. We also compared disease-specific survival using uni- and multivariate analyses.We found no significant differences between the groups regarding second recurrence or regarding the site(s) of recurrence. We also found no significant differences in disease-specific survival between the two RT groups. However, patients who did not receive chemotherapy after the initial surgery and before RT had significantly longer survival (P=0.015).In patients with locally recurrent rectal or gynecological cancer, we found no significant difference in second recurrence or survival between the local tumor only RT field and the whole pelvic RT field.

The most common secondary cancer is contralateral breast (CLB) cancer after whole breast irradiation (WBI). The aim of this study was to quantify the reduction of CLB dose in tangential intensity modulated radiotherapy (t-IMRT) for WBI using flattening-filter-free (FFF) beams.We generated automated planning of 20 young breast cancer patients with limited user interaction. Dose-volume histograms of the planning target volume (PTV), ipsilateral lung, heart, and CLB were calculated. The dose of PTV, the most medial CLB point, and the CLB point below the nipple was measured using an ionization chamber inserted in a slab phantom. We compared the two t-IMRT plans generated by FFF beams and flattening-filter (FF) beams.All plans were clinically acceptable. There was no difference in the conformal index, the homogeneity for FFF was significantly worse. For the ipsilateral lung, the maximum dose (DT-IMRT planning using FFF reduced the measured out-of-field dose of the most medial CLB point and the CLB point below the nipple.

BACKGROUND/AIM To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) correspond to poor survival in esophageal squamous cell cancer (ESCC) patients treated with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS A total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed. RESULTS In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index

Intensity-modulated radiation therapy (IMRT) delivers an excellent dose distribution compared with conventional three-dimensional conformal radiation therapy (3D-CRT) for postoperative radiation including the lymph nodes in breast cancer patients. The TomoTherapy system, developed exclusively for IMRT, has two treatment modes: TomoDirect (TD) with a fixed gantry angle for beam delivery, and TomoHelical (TH) with rotational beam delivery. We compared the characteristics of TD with TH and 3D-CRT plans in the breast cancer patients. Ten consecutive women with left breast cancer received postoperative radiation therapy using TD including the chest wall/residual breast tissue and level II–III axial and supraclavicular lymph node area. Fifty percent of the planning target volume (PTV) was covered with at least 50 Gy in 25 fractions. TD, TH and 3D-CRT plans were created for each patient, with the same dosimetric constraints. TD and TH showed better dose distribution to the PTV than 3D-CRT. TD and 3D-CRT markedly suppressed low-dose spread to the lung compared with TH. Total lung V5 and V10 were significantly lower, while V20 was significantly higher in the TD and 3D-CRT plans. The mean total lung, heart and contralateral breast doses were significantly lower using TD compared with the other plans. Compared with 3D-CRT and TH, TD can provide better target dose distribution with optimal normal-organ sparing for postoperative radiation therapy including the chest wall/residual breast tissue and lymph node area in breast cancer patients. TD is thus a useful treatment modality in these patients.

Background/Aim: To investigate the role and outcomes of radiation therapy (RT) for stage IVB uterine cervical cancer (UCC) patients with lung (oligo) metastases due to the lack of recent reports on the subject. Patients and Methods: The cohort for this retrospective study comprised 23 consecutive patients with UCC (squamous cell carcinoma, n=13) and lung metastases who had received pelvic RT. Ten had lung metastases only, including 7 with oligometastases (≤4 lung metastases); the remaining 13 also had other distant metastases. Results: Nine (39.1%) of the 22 patients (95.7%) completed RT without interruption. The 1-year primary progression-free rate was 95.2%. The 1-year overall survival rate was 47.2 % (estimated median survival: 9 months). Significant prognostic factors for survival included: i) ≤4 lung metastases (p=0.035), ii) unilateral lung metastases (p=0.039), iii) primary tumor diameter

Background The relationship between radiation dose to the ipsilateral lung and subsequent radiation-induced lung disease (RILD) in breast cancer patients with pectus excavatum (PE) undergoing radiation therapy (RT) to residual breast tissue after breast-conserving surgery has not yet been established. The incidence of RILD in such patients with PE, meaning that a large volume of the lung is within the radiation field, has not been determined. Therefore, the aim of this study was to determine the relationship between these factors. Methods The study cohort comprised 133 women who underwent three-dimensional conformal RT to residual breast tissue after breast-conserving surgery for breast cancer. Diagnoses of PE were based on Haller's, frontosagittal, and Monden's depression indices. Radiation doses to the ipsilateral lung were established from dose-volume histograms. Results Fifty of the 133 participants (37.6%) were diagnosed with RILD; all were asymptomatic. Multivariate analysis revealed a significant correlation between the incidence of RILD and the administration of > 30 Gy (V30). Surprisingly, although patients with PE received higher ipsilateral lung doses, they were less likely to develop RILD than those without PE. Conclusions Our data indicate that the incidence of RILD is correlated with the administration of > 30 Gy (V30) and that PE is not a risk factor for RILD after RT to residual breast tissue after breast-conserving surgery for breast cancer. Surprisingly, individuals with PE may have a lower incidence of RILD than those without this condition.

Background The relationship between radiation dose to the ipsilateral lung and subsequent radiation‐induced lung disease (RILD) in breast cancer patients with pectus excavatum (PE) undergoing radiation therapy (RT) to residual breast tissue after breast‐conserving surgery has not yet been established. The incidence of RILD in such patients with PE, meaning that a large volume of the lung is within the radiation field, has not been determined. Therefore, the aim of this study was to determine the relationship between these factors. Methods The study cohort comprised 133 women who underwent three‐dimensional conformal RT to residual breast tissue after breast‐conserving surgery for breast cancer. Diagnoses of PE were based on Haller's, frontosagittal, and Monden's depression indices. Radiation doses to the ipsilateral lung were established from dose‐volume histograms. Results Fifty of the 133 participants (37.6%) were diagnosed with RILD; all were asymptomatic. Multivariate analysis revealed a significant correlation between the incidence of RILD and the administration of > 30 Gy (V30). Surprisingly, although patients with PE received higher ipsilateral lung doses, they were less likely to develop RILD than those without PE. Conclusions Our data indicate that the incidence of RILD is correlated with the administration of > 30 Gy (V30) and that PE is not a risk factor for RILD after RT to residual breast tissue after breast‐conserving surgery for breast cancer. Surprisingly, individuals with PE may have a lower incidence of RILD than those without this condition.

Background/aim This study aimed to evaluate the outcome of radiation therapy for patients with distant lymph node (LN) metastases, without organ metastases from uterine cervical cancer (UCC). Patients and methods Twenty-six patients with UCC with distant LN metastases received radiotherapy and were retrospectively analyzed. The sites of distant LN metastasis were as follows; Supraclavicular in 19, inguinal in nine, axillary in four, and others in three. The mean dose prescribed for these was 50 (range=40-60) Gy. Results The 2-year overall, cause-specific, and progression-free survival, and local control of primary tumor rates were 51.3%, 51.3%, 46.9%, and 67.9%. In multivariate analysis, performance status ≥1 (p=0.007), para-aortic LN metastases (p=0.001), and lack of high-dose-rate intracavitary brachytherapy (p=0.033) were significantly associated with poor overall survival. Performance status ≥1 (p=0.004), and para-aortic LN metastases (p=0.014) were significantly associated with poor cause-specific survival. Conclusion This study demonstrated favorable local control in patients with UCC with distant LN metastases.

Background We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC). Methods We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n = 66; SCRT group: n = 18). Results The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6, 95% CI: 62.7–85.2; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2, 95% CI: 64.2–86.4; SCRT: 42.0, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P P Conclusions This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for advanced esophageal cancer, but it may be more invasive in the elderly and definitive radiotherapy (RT) alone may be selected. This study assessed the significance of sequential chemoradiotherapy (SCRT) in elderly esophageal cancer patients. Methods We reviewed 87 patients aged 75 years and older, who were treated using definitive radiotherapy without concurrent chemotherapy for esophageal cancer. A total dose ranging from 50.4 to 63 Gy (median, 58.8) was delivered to the primary lesion and the involved lymph nodes. This study compared patients who received SCRT with those who received RT alone among 40 patients with stage III or IVA cancer. Descriptive statistics were calculated using Cox proportional hazards regression analysis and the generalized Wilcoxon test. Results The total progression-free survival (TPFS), progression-free survival outside the irradiation field, and overall survival were significantly longer after SCRT (n = 15) than after definitive RT alone (n = 25; P = 0.0041 and 0.0098), whereas the progression-free survival in the irradiation field was not significantly different between the two groups. The TPFS was significantly shorter in patients who received RT alone than in those who received SCRT (P = 0.0372). There were no grade 4 or higher adverse events in the patients who received SCRT. Conclusion SCRT was associated with a reduced relapse rate, suggesting that it should be considered for markedly elderly patients with advanced esophageal cancer.

Purpose The aim of this analysis was to compare acute and late toxicities between low-dose-rate brachytherapy (LDR-BT) (110 Gy) in combination with 45 Gy in 25 fractions external beam radiation therapy (EBRT) and LDR-BT (160 Gy) alone for localized prostate cancer. Material and methods One hundred five consecutive patients with localized prostate cancer treated from May 2014 to May 2017 were included in this retrospective analysis. Sixty patients received combination therapy and 45 patients received BT monotherapy. The LDR-BT procedure was performed using 125I seeds. Results The median follow-up time was 28 months in both groups. Three-year effect rates were overall survival: 100% in both groups. The biochemical failure rate was 2.3% in the combination group and 0% in the monotherapy group (p = 0.373). No patients died during the study period. In both groups, almost all the patients experienced acute urethritis. There was a significant difference between the combination therapy group (8.3%) and BT monotherapy group (11.1%) in late genitourinary (GU) toxicities ≥ grade 2 (p = 0.035). Only 2 patients (3.3%) in the combination therapy group developed late ≥ grade 2 rectal hemorrhage. There were no significant differences between two groups in hematuria ≥ grade 2 (p = 0.068) or rectal hemorrhage ≥ grade 2 (p = 0.206). Conclusions To our knowledge, this is the first report to compare the GU and gastrointestinal toxicities between the combination therapy and BT monotherapy (160 Gy) for localized prostate cancer. Unexpectedly, there were more late GU toxicities (except for hematuria) in the BT monotherapy group.

Background Local radiation therapy (RT) can provide pain relief and reduce bleeding resulting from pleural or peritoneal dissemination of primary tumors. However, the optimal RT exposure dose for such tumors is unclear and the response rate is unknown. In this study, we examined the effectiveness of palliative RT for pleural or peritoneal disseminated tumors to determine the optimal dose in these patients. Methods The data of 22 patients with pleural- or peritoneal-disseminated tumors who were treated with local RT at our institution between 2011 and 2019 were retrospectively reviewed. Results Among these patients, 9 (40.9%) had pleural tumors, 13 (59.1%) had peritoneal tumors and 2 had tumors in the peritoneum and umbilicus. The most common primary tumors were lung (22.8%) and pancreatic cancer (18.2%). RT was mainly administered for pain alleviation (72.7%). Three patients (13.6%) received RT for hemostasis. Thirteen patients (59.1%) received a regimen of 30 Gy/10 fractions (fr), with the total dosage for all patients ranging from 27 to 56 Gy. No grade 2 or higher RT-related adverse events occurred. Three and four patients obtained complete and partial responses, respectively. The timing of the measurement of response to pain relief ranged from 0 to 232 (median, 21) days upon completion of RT. Overall response to pain relief occurred in nine of 16 patients (56.3%) with pain before RT. Hemostasis was confirmed in 2 of the 3 patients (66.7%) with bleeding before RT. Twelve of 20 (60%) patients with symptoms before RT responded to RT. Disease-specific survival (DSS) time after RT ranged from 1 to 656 (median, 106) days. Conclusions Prompt palliative administration of RT to patients with advanced disease to alleviate pain from disseminated tumors may achieve therapeutic efficacy.

Aim To evaluate whether patients with T1 esophageal squamous cell carcinoma receiving definitive radiotherapy can be managed without concurrent chemotherapy, and the role of 18F-fluorodeoxyglucose positron-emission tomography with computed tomography (FDG-PET/CT) in demonstrating local control (LC). Patients and methods Twenty-four out of 37 patients with newly-diagnosed T1 EC treated with definitive radiotherapy between July 2009 and July 2016 were retrospectively analyzed. FDG-PET/CT was performed before treatment. Eleven patients were assigned to a concurrent chemoradiotherapy (CRT) group. Thirteen were placed in a no-CRT group. The two groups were compared and univariate analysis of clinical factors influencing the prognosis in each group was conducted. Results Mean radiotherapy doses were 59.2 Gy in the no-CRT group and 55.5 Gy in the CRT group (p=0.025). Overall survival, disease-free survival, and LC rates at 2 years were lower in the no-CRT group compared to the CRT group. Disease-free survival and LC rates at 2 years were significantly lower in the patients with FDG-avid primary tumor in the no-CRT group (p=0.002 and p=0.002, respectively). All patients with FDG-avid primary tumors in the no-CRT group developed local recurrence. Conclusion It is important to note that all patients with FDG-avid primary tumor in the no-CRT group developed local recurrence. This would suggest that concurrent chemotherapy is an integral part of disease management in patients with T1 esophageal squamous cell carcinoma.

// Masaharu Hata 1, 2 , Izumi Koike 2 , Etsuko Miyagi 3, 4 , Reiko Numazaki 4, 5 , Mikiko Asai-Sato 4 , Hisashi Kaizu 2 , Yuki Mukai 2 , Shoko Takano 2 , Eiko Ito 2 , Madoka Sugiura 2 and Tomio Inoue 2 1 Division of Radiation Oncology, Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 2 Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 3 Division of Gynecologic Oncology, Department of Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 4 Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan 5 Department of Obstetrics and Gynecology, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan Correspondence to: Masaharu Hata, email: mhata@syd.odn.ne.jp Keywords: cervical cancer; radiation therapy; stage IVA; uterine cervix; vesicovaginal fistula Abbreviations: Biological effective dose, BED; high-dose-rate, HDR; computed tomography, CT; Radiation Therapy Oncology Group, RTOG Received: September 11, 2017 Accepted: October 27, 2017 Published: December 01, 2017 ABSTRACT Purpose: To evaluate the safety and efficacy of radiation therapy for stage IVA uterine cervical cancer and to identify an optimal radiation regimen. Results: Seventeen of the 28 patients developed recurrence after radiation therapy (local recurrence in 10 and distant metastasis in 12). The local control and distant metastasis-free rates at 3 years in all patients were 61% and 49%, respectively. Fourteen patients died after radiation therapy, and all but 2 died of tumor progression. The disease-free, cause-specific, and overall survival rates at 3 years in all patients were 32%, 49%, and 45%, respectively, and the estimated median survival time was 32 months. Tumor size ( P = 0.007) and involvement in the lower third of vagina ( P = 0.006) were significant prognostic factors for local control. Older age ( P = 0.018) and performance status ( P = 0.020) were significant prognostic factors for distant metastasis. The presence of hydronephrosis was the sole significant prognostic factor for survival ( P = 0.026). Only 2 patients developed grade 3 late toxicities (vesicovaginal fistula and radiation proctitis, respectively). Materials and Methods: Twenty-eight patients with stage IVA uterine cervical cancer received radiation therapy. All patients initially received external pelvic irradiation at a median dose of 50.4 Gy in 28 fractions. Twenty patients also received high-dose-rate intracavitary brachytherapy at a median dose of 22 Gy in 4 fractions. These fraction sizes were lower than conventional sizes. The total median dose for all 28 patients was 68.7 Gy. Conclusions: Radiation therapy is safe and effective for treatment of stage IVA uterine cervical cancer. The reduced radiation dose per fraction may contribute to the prevention of vesicovaginal fistula formation.

Background/Aim: The aim of this study was to define the outcome of radiation therapy for vulvar carcinoma, and to investigate the effectiveness of therapeutic and prophylactic inguinal lymph node (ILN) irradiation. Because reports about the treatment of ILN were limited. Patients and Methods: Thirty consecutive vulvar carcinoma patients were treated using external beam radiation therapy (EBRT) for definitive disease (n=25) or postoperatively (n=5). Twenty-four (80%) had squamous cell carcinoma (SCC). Tumor stages (2002 UICC) ranged from 0 to IVB, with no distant metastases. Results: The median total prescribed dose for primary tumor was 64.8 Gy. The 2-year overall survival rate was 25.3%. The outcome was significantly better in patients with ILNs60 Gy (p=0.002). Conclusions: ILN diameters ≤30 mm and prescribed doses over 60 Gy were associated with ILN control in patients with vulvar carcinoma.

To evaluate whether factors related to the clinical staging of lymph node (LN) metastasis diagnosed byA total of 69 patients with curative intent and no prior treatment for ESCC or simultaneous treatment for synchronous cancers were investigated. A maximum standardized uptake value (SUVmax) on the highest image pixel in the LN ≥2.5 was considered positive. Location of the involved LN and its impact on survival were analyzed.In the univariate analysis of location, metastasis of the abdominal site, regional abdominal LN, and left gastric LN station negatively affected overall survival (OS) and disease-free survival (DFS). Other adverse clinical factors influencing OS included T4, clinical stage IVA and body mass index21.2. In terms of DFS, a further unfavorable factor was primary tumor SUVmax ≥10.4. Abdominal site LN metastasis affected both OS and DFS in multivariate analysis.LN metastasis diagnosed by PET/CT in abdominal sites was an independent predictor affecting both OS and DFS in ESCC patients who underwent curative CCRT.

Background/aim Autologous hematopoietic stem cell transplantation (ASCT) after high-dose chemotherapy is used to treat relapsed malignant lymphomas. Radiation therapy (RT) is applied after ASCT. We compared the incidence of myelosuppression after RT with and without autologous peripheral blood stem cell transplantation (auto-PBSCT). Patients and methods We retrospectively analyzed 20 patients with malignant lymphomas who received RT, six of whom underwent auto-PBSCT. Univariate analysis using Pearson's Chi-squared test and multivariate analysis using the Cox proportional hazards regression model were performed to determine correlations between the development of grade two or more leukopenia and clinical factors. Results Among patients with auto-PBSCT, grade two or more leukopenia occurred in five. The incidence of grade two or more leukopenia was significantly higher in patients with auto-PBSCT than in those without (p=0.014). Conclusion Hematopoietic functions after auto-PBSCT may be more vulnerable to RT than normal hematopoietic functions.

Aim We aimed to retrospectively investigate the outcomes and pathological effects of retrograde superselective intra-arterial chemoradiotherapy (IACRT) combined with hyperthermia on metastatic lymph nodes of patients with oral squamous cell carcinoma. Patients and methods Patients with lymph node metastasis from oral cancer were treated with IACRT using cisplatin plus docetaxel combined with hyperthermia prior to surgical removal 8 weeks after completion of IACRT and hyperthermia. The locoregional control and overall survival rates were calculated using the Kaplan-Meier method. Results A total of 35 patients received the combination therapy of whom 26 received it as definitive treatment and in the rest, it was administered as preoperative treatment. The 5-year locoregional control and overall survivaI rates were 95.6% and 80.2% in the definitive-treatment group, and 100% and 66.6% in the preoperative-treatment group, respectively. Conclusion The combination therapy provided good outcomes in patients with lymph node metastases from advanced oral cancer.

Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI–RIST). Different institutes adopt different approaches for the administration of TBI–RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI–RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI–RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI–RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI–RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI–RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI–RIST in Japan and can assist future efforts to standardize TBI–RIST treatment methods and to design a future multicenter collaborative research study.

Background: It is now well-established that esophageal cancer can be more accurately classified macroscopically on the basis of endoscopic rather than esophagographic findings. Thus far, no studies have reported correlations between responses to radiation therapy (RT) and endoscopically-determined macroscopic type of locally advanced esophageal cancer. In this retrospective study, we therefore aimed to determine such correlations in patients who had undergone at least two follow-up endoscopies. Methods: Our study cohort comprised 30 patients who had received radiotherapy for locally advanced squamous cell carcinoma (SCC) of the esophagus from January 2012 to November 2017 at our hospital. The lesions had been classified endoscopically into one of the five types specified by the Guidelines for Clinical and Pathologic Studies on Carcinoma of the Esophagus of the Japanese Society for Esophageal Disease. All patients had received radiotherapy and 27 had received chemotherapy. In accordance with those guidelines, responses to treatment were evaluated endoscopically, a median of 74 days after initiating radiotherapy. Follow-up endoscopy had been performed at least twice in 18/30 patients. Results: The primary complete response (CR) rate was significantly higher in patients with type 1 disease (protruding) than in those with the other types (χ 2 test, P=0.041). The only correlation revealed by logistic regression analysis was between CR rate and macroscopically classified type 1 disease (P=0.05). Disease-specific survival (DSS) did not differ between macroscopically classified types (P=0.31). Patients with clinical T2 disease and ≤ stage IIIA had better outcomes than those with other stages (P=0.041 and 0.025, respectively). Conclusions: Macroscopic classification of esophageal carcinoma by endoscopy accurately identifies a group with a higher primary CR rate to chemoradiotherapy (CRT): those with type 1 disease (protruding). However, median DSS did not differ between patients with type 1 disease and those with other types.

AIM To determine the role of radiation therapy for patients with bone metastasis from uterine cervical cancer and identify an optimal radiation regimen. PATIENTS AND METHODS A total of 20 patients with bone metastases from uterine cervical cancer received radiation therapy to the pelvis. The median total dose of 60.2 Gy in the 2 Gy per fraction-equivalent dose (EQD2) was delivered to cervical tumors of all patients. Thirteen patients underwent chemotherapy during and/or following radiation therapy. RESULTS In 18 of 20 patients, the primary tumors disappeared or were markedly reduced after radiation therapy. In all but one of 17 patients with pelvic pain and bleeding, these symptoms disappeared or were remarkably relieved. However, three patients had primary tumor progression at 7, 9, and 15 months after irradiation with total doses of 56.8, 58.4, and 68.3 Gy in EQD2, respectively. Two of these patients had relapses of bleeding and pain. The primary progression-free rate considering all patients was 69% at 1 year and 34% at 2 years. The corresponding overall survival rates were 34% at 1 year, and 8% at 2 years, with an estimated median survival time of 7 months. The number of metastatic bone sites (p=0.027) and administration of chemotherapy (p

Angiosarcoma, a rare cutaneous malignancy, frequently arises in the scalp of older individuals. Because it characteristically initially mimics benign disease, such as a bruise, definitive diagnosis in the early stages is difficult. Angiosarcoma of the scalp is highly malignant and often accompanied by lung metastases that cause hemopneumothorax. Although surgery has been the standard and most reliable curative treatment for angiosarcoma of the scalp, there is a high probability of local recurrence, even after wide surgical excision. Therefore, postoperative radiation therapy has been administered in an attempt to minimize local recurrence. However, surgery is contraindicated in many older patients because of severe comorbidities or age. Definitive radiation therapy has been administered to such patients and has achieved good local control. In particular, total scalp irradiation may be a promising option for curative treatment of angiosarcoma of the scalp. Recent reports suggest that chemotherapy, particularly with taxanes, can prolong survival by reducing the rate of distant failure after radiation therapy. Thus, radiation therapy along with chemotherapy is now recommended for curative treatment of patients with inoperable disease and even some patients with operable disease. Technological developments in radiation therapy, such as intensity-modulated radiation therapy, will contribute to enhanced efficacy and reduced toxicities in the treatment of patients with angiosarcoma of the scalp.

Objectives To evaluate the therapeutic results and rate of organ preservation in patients with squamous cell carcinoma of the tongue treated with retrograde superselective intra-arterial chemoradiotherapy. Materials and methods Between June 2006 and June 2015, 118 patients with tongue cancer were treated with intra-arterial chemoradiotherapy. Treatment consisted of radiotherapy (total 50–70 Gy) and daily concurrent intra-arterial chemotherapy (docetaxel, total 50–70 mg/m2; cisplatin, total 125–175 mg/m2) for 5–7 weeks. Locoregional control and overall survival rates were calculated by the Kaplan-Meier method. Cox’s proportional hazards model was used for both univariate and multivariate analyses. Results The median follow-up for all patients was 38.5 months (range, 3–129 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 113 (95.8%) of 118 cases. Three-year locoregional control and overall survival rates were 80.3% and 81.5%, respectively. Grade 3 or 4 toxicities included neutropenia in 16.1% and mucositis in 87.3%. Grade 3 toxicities included anemia in 12.7%, thrombocytopenia in 3.4%, nausea/vomiting in 3.4%, dermatitis in 45.7%, dysphagia in 74.6%, and fever in 2.5% of patients. Late toxicity consisting of grade 3 osteoradionecrosis of the jaw occurred in 4.2% of patients. On univariate analysis, T stage and overall stage were significantly associated with locoregional control, and N stage and overall stage were significantly associated with overall survival. On multivariate analysis, the only significant predictor of overall survival was overall stage classification. Conclusion Retrograde superselective intra-arterial chemoradiotherapy for tongue cancer provided good overall survival and locoregional control.

Background The aim of this retrospective observational study was to evaluate toxicities, overall survival, and locoregional control in elderly oral squamous cell carcinoma patients who had undergone retrograde intra-arterial chemotherapy combined with radiotherapy. Methods Thirty-one elderly patients over 80 years old with oral squamous cell carcinoma were enrolled in present study. The treatment schedule consisted of intra- arterial chemotherapy (docetaxel, total 60 mg/m2; cisplatin, total 150 mg/m2) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. Results The median patient age was 82.5 years old (range, 80–88 years). Of the 31 patients, six (19%) had stage II, 6 (19%) had stage III, 17 (55%) had stage IVA, and 2 (6%) had stage IVB. The median follow-up period for all patients was 37 months (range, 7–86 months). The 3-year overall survival and locoregional control rates were 78% and 81%, respectively. The major acute grade 3 adverse events were oral mucositis in 22 (71%) patients, neutropenia in 16 (52%), and dermatitis in 11 (35%). With respect to late toxicities, 1 patient (3%) developed grade 3 osteoradionecrosis of the jaw. No grade 4 or higher toxicities were observed during the treatment and follow-up periods. Conclusions Retrograde intra-arterial chemotherapy combined with radiotherapy was effective in improving overall survival and locoregional control even for elderly patients.

A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010–2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source–surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors.Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B).Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS.Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.