The purpose of this study was to prospectively clarify the safety and efficacy of the combination therapy of stereotactic body radiotherapy on a thoracic lesion and PD-1 blocker in patients with metastatic non-small cell lung cancer. This is a prospective phase I study performed in the single institution. Metastatic histologically-proven non-small cell cancer patients with at least two measurable lesions including one or more in the thorax were enrolled in the study. The treatment protocol was the combination of an administration of totally 12 courses of nivolumab (3 mg/kg, every 2weeks) and stereotactic body radiotherapy (SBRT) on one of thoracic metastases at the 3rd course of nivolumab. Single dose of SBRT was set more than 5 Gy and total biological effective dose (BED, alfa / beta was 10 Gy) was decided from 40 Gy to 55 Gy as much as possible according to the dose constraints for critical organs nearby irradiated lesion. The primary endpoint was the ratio of cases with grade 3 or more toxicity using CTCAE ver. 4.0 within 24 weeks after the start of the therapy. The secondary endpoints were the tumor responses using RECIST 1.1 of the irradiated and non-irradiated lesions at 24 weeks after start of treatment. If the result reached the dose limiting toxicity (grade 4 and 5 adverse effects or the grade aggravation by 3 or more compared to pre-treatment status in one of six cases) at the time when six patients registered, the dose of SBRT would be deceased in next 6 patients. But if not, the treatment protocol would be judged as feasible and the patient registration would be stopped in the study design. The result did not reach the dose limiting toxicity at the time when six patients registered, and therefore totally 6 patients (gender; 4 male and 2 female, age; 54-84 year old, histology; adenocarcinoma in all) were enrolled in the study, but 3 patients could not complete full of the treatment due to disease progression in two patients and grade 3 pneumonitis in one patient. SBRT dose / fractionation were 24 Gy / 2 fractions in 3 patients, 24 Gy / 3 fractions in 2 patients, and 29.6Gy / 4 fractions in 1 patient. Regarding toxicity, grade 3 pneumonitis occurred in one patient but no other adverse events more than grade 2 were observed. Local response of the irradiated lesion was complete remission in 1 patient, partial remission in 2 patients, and stable disease in 3 patients. The response of the non-irradiated lesions response was partial remission in 1 patient, stable disease in 2 patients, and progressive disease in 3 patients. The overall survival at 1 and 2 years were 83.3% and 62.5%, respectively. The combined therapy of 12 courses of nivolumab and SBRT on thoracic lesion at the 3rd course for the patients with metastatic non-small cell lung was feasible. The survival might be promising in comparison with previous reports of stage IV patients in spite of the advanced status after other treatments. Prospective phase II study is mandatory to examine our conclusion.

Increasing evidence has suggested that systemic inflammation and nutrition are related to clinical outcome in patients with various cancers including lung cancer. Hence, we assessed the prognostic value of pretreatment modified Glasgow prognostic score (mGPS), the combination of C-reactive protein (CRP) and albumin, in patients with stage I non-small lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT). We performed a single-institution retrospective cohort study on patients treated with SBRT for stage I NSCLC between 2008 and 2016. Patients who had no laboratory data within 3 months before SBRT were excluded. mGPS value was defined as follows: mGPS 0: CRP ≤ 0.1 and albumin > 3.5, mGPS 1: CRP > 0.1 and albumin > 3.5 or CRP ≤ 0.1 and albumin ≤ 3.5, and mGPS 2: CRP > 0.1 and albumin ≤ 3.5. The patients were divided into two groups: low mGPS group (mGPS: 0) and high mGPS group (mGPS: 1-2). The clinical outcome was evaluated based on 3-year progression-free survival (PFS), cause-specific survival (CSS) and overall survival (OS). PFS, CSS and OS were calculated using the Kaplan-Meier method, and examined with the log-rank test. Prognostic factors including age, sex, histology, T stage and mGPS were examined with univariate and multivariate analyses using Cox proportional hazards model. Totally 148 patients (103 men and 45 women) with stage I (UICC 7th, T1aN0M0: 51, T1bN0M0: 35, T2aN0M0: 62) were included in this study. The median age was 80 years old (range, 53-90). The median follow-up duration after SBRT was 34 months (range, 2-124). The histology was adenocarcinoma in 72, squamous cell carcinoma in 33, other carcinoma in 8, and no pathological diagnosis in 35 patients. Finally, 47 patients were dead, and the causes were cancer-specific in 10, intercurrent disease in 19, and unknown in 18 patients. Eighty-one patients were low mGPS group, and 67 were high mGPS group. The 3-year PFS, CSS and OS for all patients were 60%, 92% and 74%, respectively. The 3-year PFS, CSS and OS in low and high mGPS groups as follows: 3-year PFS: 68% and 49% (P < 0.05), 3-year CSS: 91% and 95% (P = 0.76), and 3-year OS: 82% and 63% (P < 0.05), respectively. In both of univariate and multivariate analyses, mGPS was a significant factor for PFS and OS. The pretreatment mGPS is a predictor of PFS and OS in stage I NSCLC patients treated with SBRT. Low mGPS indicates better PFS and OS in these patients.

The purpose of this study was to clarify the prognosis after recurrence or metastases on local tumor, regional lymph node, or distant organ in medically operable stage I non-small cell lung cancer NSCLC patients treated by stereotactic body radiotherapy (SBRT). We organized a multi-institutional SBRT study group of 20 institutions in Japanese Radiological Society (JRS-SBRTSG) and conducted a retrospective analysis to review 156 medically operable patients (median age, 75 years; male 119, female 37; adenocarcinoma 83, squamous cell carcinoma 37, others 36) who were treated with SBRT for stage I (IA 100, IB 56) NSCLC, and had local recurrence or metastases on somewhere of regional lymph node or distant organ. A total dose of 36 -70 Gy mainly at the isocenter was prescribed in 4-15fractions. The median calculated biological effective dose (BED) was 108 Gy (range, 64-150 Gy) based on alpha/beta = 10Gy). Local recurrence and metastases were judged according to continuously increasing in size or 18F-FDG PET-positive finding. The survival curves of local tumor, regional lymph node, and distant organ were calculated using Kaplan-Meir method. The median follow-up period was 36 months. At the last observation period, the cases of local tumor recurrence, regional lymph node metastases, and distant organ metastases were 60 cases, 67 cases, and 107 cases respectively. Combined other sites recurrence or metastases was found in 61.7%, 70.1%, and 51.4% of the recurrence local recurrence, regional lymph node metastases, and distant organ metastases, respectively. The mean times to the local recurrence, regional lymph node metastases, and distant organ metastases from the start of SBRT were 23 months, 17 months, and 22 months, respectively. The mean survival times after the local recurrence, regional lymph node metastases, and distant organ metastases were 21 months, 13 months, and 12 months, respectively. The mean survival times after isolated local recurrence, regional lymph node metastases, and distant organ metastases were 22 months, 17 months, and 13 months, respectively. The overall survival rate was statistically better in female group than male group after the lymph node or distant organ metastases, but not different after the local recurrence. The survival rate was not different after any recurrence or metastases between stage IA versus IB nor adenocarcinoma versus squamous cell carcinoma. The survival time after the recurrence or metastases in medically operable stage I NSCLC treated by SBRT was short in order of distant organ metastases, regional lymph node metastases, and local recurrence. This result provided a useful information for prediction of the prognosis after the recurrence or metastases.

Recent studies showed that neutrophil-related cytokines could promote cancer metastases or progression. On the other hands, it is well known that lymphocytes inhibit cancer progression. Here, we assessed whether pretreatment neutrophil-to-lymphocyte ratio (NLR) associated with prognosis in patients with stage I non-small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). We retrospectively reviewed patients treated with SBRT for stage I NSCLC between 2008 and 2016. Patients who had no blood tests within 3 months before SBRT were excluded. We divided the patients into two groups according to NLR cutoff value using receiver operating characteristic (ROC) analysis. Primary outcome was 3-year metastases free survival (MFS) including lymph node or distant metastases, and secondary outcomes were 3-year progression free survival (PFS), cause-specific survival (CSS) and overall survival (OS). These outcomes were calculated using the Kaplan-Meier estimates, and examined with the log-rank test. Prognostic factors including age, sex, pathology, T stage and NLR were analyzed with univariate and multivariate analyses using Cox proportional hazards model. Totally 157 patients (110 men and 47 women) with stage I (UICC 7th, T1aN0M0: 54, T1bN0M0: 39, T2aN0M0: 64) were enrolled in this study. The median age was 80 years old (range, 53-90). The median follow-up time after SBRT was 36 months (range, 2-124). The histology was adenocarcinoma in 78, squamous cell carcinoma in 34, other carcinoma in 9, and no pathological diagnosis in 36 patients. NLR was divided into higher group (> 2.8) in 104, and lower group (≤ 2.8) in 53 patients according to the result of ROC analysis. Disease progression was observed in 49 patients and 39 of them had metastases. Finally, 53 patients were dead, and the causes were cancer-specific in 13, intercurrent disease in 21, and unknown in 18 patients. The 3-year MFS, PFS, CSS and OS for all patients were 63%, 59%, 93% and 75%, respectively. The 3-year MFS, PFS, CSS, and OS in lower and higher NLR groups as follows: 3-year MFS: 72% and 46% (p < 0.05), 3-year PFS: 65% and 47% (p < 0.05), 3-year CSS: 97% and 84% (p = 0.29), and 3-year OS: 84% and 59% (p < 0.05), respectively. In univariate analysis, NLR was a significant factor for MFS, PFS and OS. In multivariate analysis, lower NLR was associated with better MFS (p < 0.05, HR: 0.45, 95% CI: 0.27-0.75) and PFS (p < 0.05, HR: 0.53, 95% CI: 0.33-0.86) after adjusting for other prognostic factors. Pretreatment NLR is an independent prognostic factor of MFS and PFS in patients with stage I NSCLC underwent SBRT. Lower NLR indicates low risk of lymph node and distant metastases in these patients.

Deep inspiration breath-hold (DIBH) technique is effective in reducing heart dose compared to a free-breathing technique in the treatment for left side breast cancer. The purpose of the study was to show the workflow and the accuracy of our new irradiation method for it with a combination of a respiration monitoring device and body surface monitoring system. For the workflow of the treatment, first, a patient practiced DIBH during the CT simulation using a respiration monitoring device that could recognize the patient's own respiratory phase using audio or visual guidance. Then, a CT scan was taken under the DIBH condition and treatment plan of tangential two opposed fields was made. In the treatment, patient-setup was performed by adjusting the body surface-scanned image to the reconstructed surface image made of the planning CT images. Audio guidance was used to accomplish the DIBH. For the evaluation of the accuracy of this method, totally 150 irradiations in three patients were analyzed. Inter-fractional positioning errors was calculated in comparison of planning CT images with the fractional CBCT images per a week. Intra-fractional organ motions were calculated in comparison of the digitally reconstructed radiograph (DRR) made of planning CT images with the actual portal MV-cine image taken under DIBH in each fraction. All treatments were completed safely. The average inter-fractional positioning errors calculated form weekly CBCT images were within 2.3 mm for lateral, longitudinal, and vertical directions respectively. The intra-fractional reproducibility of the DIBH was -0.1 ± 2.0 mm and -0.2 ± 1.8 mm (n = 150 beams) in the horizontal and vertical directions, respectively. Our new DIBH method using a new combination of respiration monitoring device and optical body surface monitoring system is effective for left side breast cancer treatment with accurate inter- and intra-fractional reproducibility of the DIBH position.

The index of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with clinical outcomes for many types of carcinomas. We aimed to assess the impact of pretreatment NLR and PLR on long-term prognosis of early-stage non-small-cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT), and introduce a novel risk assessment method. We designed a single-center retrospective cohort study on patients underwent SBRT for early-stage NSCLC between 2004 and 2016. Data acquisition was through medical records, blood count recorded within 1-week before SBRT were selected to calculate the pretreatment NLR and PLR. Patients were divided into three subgroups according to median NLR (NRLm) and median PLR (PLRm). a) high risk group: ≥NRLm and ≥PLRm; b) intermediate risk group: < NRLm and ≥ PLRm, or ≥ NRLm and < PLRm; c) low risk group: < NRLm and < PLRm. Overall survival (OS) were calculated using the Kaplan-Meier method from the first day of treatment, and evaluated by the log-rank test. Cox proportional hazards model were used for univariate analyses. A total of 111 patients were included in this study. The median duration of follow-up for all patients was 42 (range from 3 to 105) months. 51 deaths were observed, and the 3-year OS and CSS for all patients were 70.1% and 83.3%, respectively. The median and range of the NLR and PLR were 2.28 (0.89-13.77) and 140.00 (51.12-568.57) respectively. High risk group patients showed a median OS of 48.2 months. In contrast, intermediate risk group and low risk group patients had a median OS of 63.4 and 68.7 months, respectively (p = 0.045). In univariate analysis, risk group, gender, histological tumor type, T-stage, and PLRm were associated with OS. Risk group and T-stage were associated with CSS. In multivariable analysis, Lower T-stage and PLR were found to be associated with higher OS. Only T-stage was significantly associated with CSS. NRLm was not independently associated with OS or CSS. We invented a novel risk assessment method using a combination of NLR and PLR, which could potentially provide a simple and inexpensive methodology for predicting the long-term survival in patients of early-stage NSCLC treated with SBRT.

We retrospectively analyzed the treatment outcome of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) in patients less than 70 years of age. We retrospectively analyzed patients with stage I (cT1-2aN0M0) NSCLC, treated with SBRT between 2000 and 2014. 43 consecutively treated patients less than 70 years of age were identified. Staging was reassessed by UICC 7th. Both biopsy-proven and clinically diagnosed stage I NSCLC were included. Overall survival (OS), cause-specific survival (CSS), local control rate (LCR), regional lymph node control rate (RLNCR), and distant control rate (DCR) were calculated and compared between subsets of patients. Kaplan-Meier estimates were utilized for survival analyses, and evaluated by the log-rank test. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scales were recorded during follow-ups and utilized for toxicity assessments. For the 43 patients included, median age was 65 years (Range: 50-69 years), median Karnofsky performance status was 100 (Range: 80-100), and median follow-up time was 58 months (Range: 7-193 months). Median prescription dose was 48 Gy in 4 fractions (Range: 48-70Gy in 4-10 fractions). The rates for OS and CSS at 5 years were 63.8% and 91.5%, respectively. The 5-year LCR, RLNCR, and DCR were 92.4%, 91.7%, 78.7%, respectively. In the subsets analysis, patients were subcategorized into Group Ia and Group Ib, according to the T-stage, or subcategorized into Operable group and Inoperable group. Although there was no significant between the groups, Group Ia, and Operable group showed a better result in OS, but not in others. Regarding treatment toxicity, severe (grade 3 or above) radiation pneumonitis occurred in 6.8% of the cases, and no other toxicities of Grade 2 or above were observed. SBRT for stage I NSCLC in patients less than 70 years of age yielded good long-term survival outcomes with acceptable toxicity.

The popularization of computed tomography (CT) in clinical practice have increased a frequency of discovering ground-glass opacity (GGO)-containing tumor in lung. Surgery has been regarded as the general treatment including a purpose of histological examination for such tumors and its prognosis is better than that of solid-type tumors. Stereotactic body radiation therapy (SBRT) is a rapidly prevailing treatment modality in the radical treatment of mainly inoperable or high risk operable cases with stage I non-small cell lung cancer (NSCLC), but the most tumors treated with SBRT were solid type because SBRT has been performed principally for the pathology-proven tumors and it is generally difficult to acquire histological specimen in the tumors composed of GGO. Therefore a prognosis of the stage I NSCLC cases treated with SBRT when their tumors contained GGO has not been clear. The purpose of this presentation is to review the treatment outcomes for SBRT for the patients with GGO-containing tumor in our multi-institutional SBRT study group of Japanese Radiological Society (JRS-SBRTSG), and to discuss how we consider the validity of SBRT for them.

The lung is a main site of metastatic disease for most solid tumors. Recently local treatments have an emerging role for oligometastatic lesions in combination with systemic therapies. The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiation therapy (SBRT) for patients with pulmonary oligometastases in the database of a multi-institutional SBRT study group in Japanese Radiological Society. This is a retrospective analysis to review totally 380 patients (median age, 69 years; male 261, female 119) with pulmonary metastases treated at 7 institutions of JRS-SBRTSG. Major organs of the primary cancers were lung in 139, colorectal in 96, esophagus in 26, kidney in 12, uterine cervix in 11, and others in 98 patients. Histology of the primary cancers was adenocarcinoma in 192, squamous cell carcinoma in 92, and others in 96 patients. Median diameter of the lung tumors treated with SBRT was 18 (range, 5-53) mm. A total dose of 20-70 Gy was administered in 1-10 fractions. The median calculated biological effective dose (BED) was 113 Gy (range, 45-150 Gy) based on alpha/beta = 10 Gy). Chemotherapy was administrated in 27% of the patients before or after SBRT. The median follow-up period for all patients was 23 (range, 1-107) months. Locally progression-free rate at 3 year (LPF-3y) of total patients and subgroups of BED<100 Gy versus BED ≥ 100 Gy were 69.1% and 54.1% versus 70.3% (no significant statistical difference: NS), respectively. LPF-3y of patients with colorectal origin was significantly worse (38.9%) than that of non-colorectal origin (82.5%; P<.0001). LPF-3-y of patients with squamous cell carcinoma was significantly better (76.5%) than that of adenocarcinoma (63.2%; P<.05). LPF 3-y of patients with the tumor diameter < 20 mm was better (71.8%) than that of > or = 20 mm (60.8%) (P=.08). Multivariate analysis demonstrated that the primary organ of the colorectum was the only significant prognostic factor for LPF. Overall survival rate at 3 year (OS-3y) of total patients and subgroups of BED <100 Gy versus BED ≥100 Gy were 64.7% and 50.9% versus 67.1% (NS), respectively. OS 3-y of patients with colorectal and non-colorectal origin was 56.1% and 69.1%, respectively (NS). OS-3y of patients with squamous cell carcinoma and adenocarcinoma were 58.0% and 63.6%, respectively (NS). OS-3y of patients with the tumor diameter <20 mm was significantly better (79.1%) than that of ≥20 mm (40.2%; P<.0001). Multivariate analysis demonstrated that the tumor diameter of less than 20 mm was the only significant prognostic factor for OS. Metastases to other organs were seen in 57.4% of the patients with the tumor diameter ≥20 mm. LPF is worse in the patients with lung metastases from colorectal origin. OS is better in the patients with the lung tumor diameter < 20 mm.

Stereotactic body radiotherapy (SBRT) for peripheral stage I non-small cell lung cancer (NSCLC) is a promising and nearly safe treatment. However, late side effects of the treatment are not well known and we have sometimes experienced rib fracture cases after SBRT. In this study, we analyzed characteristics and clinical courses of patients with and without an incidence of rib fracture after SBRT. During the period 2001-2009, a total of 177 patients with stage I (118 T1N0M0; 59 T2N0M0) NSCLC were treated with SBRT alone. Patients ranged from 56 to 92 years old (median, 78 years). Tumor size ranged from 8 to 55 mm (median, 25mm). In the treatment planning, planning target volume (PTV) was determined from gross tumor volume (GTV) by adding personal internal margin, with an additional safety margin of 5 mm. According to tumor characteristics, total dose/fractions of SBRT were grouped into three schedules: 48 Gy in 4 fractions; 60 Gy in 10 fractions; and 70 Gy in 10 fractions. The prescribed doses were calculated at the minimum dose point in the PTV using Clarkson algorithm with heterogeneity correction. The rib fracture-negative group was composed of the patients in whom rib fracture had not been observed for more than at least 24 months after SBRT. Maximum biologically effective dose (BED) for the chest wall around tumor was calculated using linear quadratic model (α/β = 3Gy). Unpaired t-test and chi-square test were used for statistical analysis. During follow-up (median, 33 months), rib fracture was detected in 41 (23.2%) of 177 patients. The interval between the incidence of rib fracture and the start of SBRT ranged from 2 to 45 (median, 12) months. The symptomatic pain requiring some pain killer drugs was observed in only 7 (17.1%) of 41 rib fracture-positive patients. No rib fracture was observed in cases of which distance between the tumor and chest wall was more than 16mm. A CT finding of chest wall edema was observed in 35(85.4%) of 41 rib fracture-positive patients. Female had a significantly higher incidence rate of rib fracture than male. Maximum BED for the chest wall ranged from 218 to 340 (median, 257) Gy in the rib fracture-positive group, and it was higher than that in the rib fracture-negative group (n = 45). Though no rib fracture occurred in the cases of which maximum BED for the chest wall was less than 218 Gy, rib fracture was inevitable in the cases of which the BED was more than 250 Gy. Rib fracture is a frequent complication after SBRT for peripherally located NSCLC, in particular for females, but symptom of most cases is negative or mild. If maximum BED for chest wall is more than 250Gy, rib fracture would be inevitable. Chest wall edema is a frequent prelude to the incidence of rib fracture.

We have utilized a technique of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using patient voluntary breath-hold method and a unit comprising CT and linear accelerator (CT-linac) in order to minimize both of internal and set-up margins. The purpose of this study was to evaluate the results by this technique and to explore an adequate dose/fractionation for the control of the tumors. In 2001-2006, a total of 105 patients with Stage I (57 T1N0M0; 48 T2N0M0) primary NSCLC (62 adeno, 28 squamous cell, and 15 others) were treated with SBRT alone. Patients ranged from 56 to 92 years old (median, 78 years). All patients exercised sufficiently how to hold the breath at a same inspiration phase. In the treatment planning, planning target volume (PTV) was determined from gross target volume (GTV) by adding personal internal margin for each patients calculated from three CT scans taken under randomly-repeated voluntary breath-holds, with an additional safety margin of 5 mm. After adjusting the isocenter of the PTV to the planned position by the CT-linac unit, irradiation was performed under patient voluntary breath-holds. In January 2001- July 2004, total dose of 60 Gy was delivered in ten fractions at the minimum dose point in the PTV using a 6 MV X-ray for all cases. In August 2004- December 2006, total dose of 48 Gy was delivered in four fractions at the isocenter for T1 cases and total dose of 70 Gy was delivered in ten fractions at the minimum dose point in the PTV for T2 cases. The dose distribution was calculated using Clarkson algorithm with heterogeneity correction. During follow-up (median, 28 months), local control rates of T1 and T2 cases at 3-year after post SBRT were 86.4% and 76.2%, respectively. Three-year overall survival rates of medically inoperable (n = 82) and operable (n = 23) patients were 44.4% and 77.4%, respectively. In T1 cases, the 3-year local control and overall survival rate of the 60 Gy in ten fractions subgroup (n = 26) were 100% and 75.4%, respectively, and they were better (p < 0.05) than those of the 48 Gy in four fractions subgroup (n = 29). In the 70 Gy in ten fractions subgroup, there was no local recurrence. Though 48 Gy in four fractions is the most common SBRT schedule for stage I NSCLC in Japan, the local control and survival rates of it were worse than those of a higher dose schedule according to our technique permitting small internal and set-up margins achieved by breath-hold method and a CT-linac unit. A yet more adequate dose / fractionation and an appropriate irradiation method of SBRT should be investigated for an ideal treatment for stage I NSCLC.

PURPOSEThe purpose of this study was to explore the effect of concurrent intra-arterial infusion of platinum drugs in patients with stage III or IV uterine cervical cancer treated with radical radiation therapy.PATIENTS AND METHODSThirty-three patients with advanced (stage IIIA, 2; IIIB, 28; IVA, 3) uterine cervical squamous cell carcinoma were randomized into a concurrent intra-arterial infusion of platinum drugs with radiation therapy (IAPRT) group (18 patients) and a radiation therapy alone group (15 patients). After altering intrapelvic blood flow by embolization of the superior and inferior gluteal arteries under pelvic angiography, intra-arterial infusion of platinum drug through catheters inserted into both internal iliac arteries was performed concurrently with radiation therapy. One-shot infusion of cisplatin (100 mg/m2) twice with a 2- to 3-week interval was performed in eight patients, weekly infusion of carboplatin (100 mg/m2) via a reservoir five to six times was performed in four patients, and daily shot of cisplatin (10 mg/body) or 21 days via a reservoir was performed in six patients. Radiation therapy consisted of external-beam irradiation of 50 Gy/25 fractions/5 weeks for the whole pelvis with midline block after 30 Gy and intracavitary high-dose-rate brachytherapy using tandem and ovoids of 24 Gy/4 fractions/4 weeks to point A.RESULTSThe local complete response rate of the IAPRT group was 94% and was significantly higher than that of the radiation therapy group (67%). There were no significant differences in local response in the three drug delivery methods. Two- and 5-year overall survival rates were 54.5% and 44.4% in the IAPRT group, and 74.5% and 50.0% in the radiation therapy group, respectively. There was no significant difference between the two groups. In the IAPRT group, grade 3 or 4 acute bowel complications were seen in 33% of patients, grade 3 or 4 late bowel complications were seen 44%, and grade 3 or 4 myelosuppression was seen in 33%, and these complications were seen more in the IAPRT group than in the radiation therapy group and caused death in some patients.CONCLUSIONSIAPRT had a better local response than radiation therapy but showed no proof of control over recurrence and had a poorer survival than radiation therapy. There were many local recurrences and distant metastases, contrary to the better first response of the IAPRT group over the radiation therapy group. Complications of the IAPRT group were very severe and made the patient's performance status and prognosis worse than in the radiation therapy group. We need to design some methods to decrease these complications to make use of the good local response acquired with IAPRT. Furthermore, we should re-examine the indication of IAPRT in patients with a large tumor because local recurrence and distant metastasis would be inevitable.