Favorable outcome of intraoperative radiotherapy to the primary site in patients with metastatic prostate cancer.

BACKGROUND: The aim of this study was to determine whether local radiotherapy to the prostate by intraoperative radiotherapy (IORT) increases the overall and cancer-specific survival rates of patients with metastatic prostate cancer. METHODS: Between 1993 and 2000, 102 patients with prostate cancer were treated with a combination of (a) IORT of the prostate (25 or 30 Gy per fraction); (b) external beam radiotherapy of the prostate (30 Gy in 10 fractions), starting approximately 1 week post-operatively; and (c) endocrine treatment. Of these, 16 patients had stage D1 disease (D1 IORT group), 32 had stage D2 disease without visceral metastasis (D2 IORT group), and 38 had stage D2 disease without visceral metastasis and did not receive local therapy (D2 control group). Overall and cancer-specific survival rates were compared. RESULTS: The 5- and 10-year cancer-specific survival rates were 75.9 and 52.7 %, respectively, in the (D1 + D2) IORT group and 45.8 and 33.5 %, respectively, in the D2 control group, with cancer-specific survival being significantly longer in the D2 IORT than in the D2 control group (P = 0.030). Univariate and multivariate reduced-rank regression analyses showed that extent of skeletal disease Grade 4 and non-regional lymph node metastasis were significantly prognostic of poorer cancer-specific survival (P < 0.001 each). CONCLUSIONS: Local radiotherapy to the prostate by IORT in patients with metastatic prostate cancer may contribute to better survival, especially in patients without extent of skeletal disease Grade 4 or non-regional lymph node metastasis.

High-dose-rate intra-cavitary brachytherapy combined with external beam radiation therapy for under 40-year-old patients with invasive uterine cervical carcinoma: clinical outcomes in 118 Patients in a Japanese multi-institutional study, JASTRO.

BACKGROUND: The current study was designed to evaluate the clinical outcomes of curative intent radiation therapy for young patients with invasive uterine cervical carcinoma in Japan. METHODS: One hundred and eighteen patients aged ≤40 were registered in the multi-institutional study of the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) from 26 major institutions in Japan. The age range was 24-39 years and the maximum tumor diameter was 2.0-9.2 cm. The International Federation of Gynecology and Obstetrics clinical stages were Ib, IIa, IIb, IIIa, IIIb and IVa in 17, 6, 40, 2, 50 and 3, respectively. Curative intent radiation therapy consisted of the combination of external beam radiation therapy and high-dose rate intra-cavitary brachytherapy. The total dose of external beam radiation therapy ranged between 44 and 68 Gy. Both the median and mode of total high-dose-rate intra-cavitary brachytherapy dose to point A were 24 Gy in four fractions. Ninety-six patients (58%) received chemotherapy. RESULTS: The 5-year overall survival rate and local control rate of all patients were 61 and 65%, respectively. The 5-year overall survival rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 88, 100, 75, 100, 37 and 0%, respectively. The 5-year local control rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 82, 75, 75, 100, 51 and 0%, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity. CONCLUSIONS: The 5-year overall survival rate of young patients with Stage IIIb was comparatively low at 37%.

Is a low dose of concomitant chemotherapy with extended-field radiotherapy acceptable as an efficient treatment for cervical cancer patients with metastases to the para-aortic lymph nodes?

INTRODUCTION: Extended-field radiotherapy (EFRT) with the concomitant administration of chemotherapy for patients with advanced cervical cancer has problems regarding its feasibility. The goal of the present study was to assess the tolerability and control rate of low-dose cisplatin with EFRT in patients with imaging-confirmed positive para-aortic lymph nodes (PALs). METHODS: Sixteen patients with cervical cancer metastatic to the PALs treated with EFRT were evaluated. The patients included those with stages I to III disease according to the International Federation of Gynecology and Obstetrics with positive PALs diagnosed by computed tomographic imaging. The patients were treated with 25 to 30 mg/m weekly of cisplatin concurrently with radiation therapy. Doses of 48.6 to 51.0 Gy were delivered in 1.8-Gy fractions to the pelvis and included the PALs field. In addition, boost doses for the involved nodes of PALs were delivered contiguously for a total dose of 54 to 60 Gy. All patients were treated with a high dose rate of intracavitary brachytherapy combined with external irradiation. RESULTS: All patients completed the radiation therapy. Grade 3 or 4 acute hematologic toxicity occurred in 7 patients, but there were no cases of grade 3 or 4 nonhematologic acute toxicity. As a late toxicity, 1 patient developed a grade 3 small bowel obstruction. No grade 4 or worse late toxicity occurred. The 4-year overall survival rate was 56.3%. The 4-year distant metastasis-free survival rate was 50%. Seven patients had no recurrence. Eight patients developed distant failures, and another had an isolated local intrapelvic recurrence. CONCLUSIONS: A dose greater than 54 Gy for positive PALs in EFRT, in combination with intracavitary irradiation and low-dose weekly cisplatin administration, was safely completed by all of our patients. However, half of the patients had distant failure. This study provided relatively favorable local control and survival. Further considering modifications of the treatment should therefore be encouraged.

Radiotherapy quality assurance of the Japanese Gynecologic Oncology Group study (JGOG1066): a cooperative phase II study of concurrent chemoradiotherapy for uterine cervical cancer.

BACKGROUND: To assess radiotherapy protocol compliance in a multi-institutional phase II study of concurrent chemoradiotherapy for patients with locally advanced cancer of the uterine cervix (JGOG1066). METHODS: For study protocol development, various radiotherapy parameters were examined and consensus was reached by Japanese radiation oncologists with cervical cancer treatment expertise. Quality assurance (QA) was also discussed and included in the protocol. A credentialing process was used to select institutions for participation in the study. Individual case reviews referring to 18 QA items were undertaken for each patient. Radiotherapy data were submitted to the Japanese Gynecologic Oncology Group (JGOG) data center and reviewed by the members of the radiotherapy committee. The QA evaluation was classed as per protocol, deviation, and violation. RESULTS: Individual case reviews were performed on 69 of 72 patients entered in the study. In 24 patients (35%), there were no deviations for any QA items. There were also no deviations seen for 5 of the 18 items in 69 patients evaluated. Deviations of 64 QA items were seen in 45 cases, and violations were seen in 4 cases (4 items). The most common deviation concerned appropriate application for the external beam radiotherapy (EBRT) boost to involved nodes or parametrium (32 cases). The 4 violations were identified in the QA items regarding high-dose rate intracavitary brachytherapy. CONCLUSIONS: Radiotherapy protocol compliance was favorable except for the EBRT boost indications. The results of this study validate the quality of radiotherapy in JGOG1066, and indicate that the final analysis will provide meaningful results.

A multi-institutional survey of the quality of life after treatment for uterine cervical cancer: a comparison between radical radiotherapy and surgery in Japan.

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.

Therapeutic effect of linac-based stereotactic radiotherapy with a micro-multileaf collimator for the treatment of patients with brain metastases from lung cancer.

OBJECTIVE: To assess the efficacy of hypofractionated linac-based stereotactic radiotherapy with a micro-multileaf collimator (mMLC) in lung cancer patients with brain metastases. METHODS: Seventy-eight lesions of brain metastases in 49 lung cancer patients treated by stereotactic radiotherapy between September 2003 and December 2006 were analyzed. In the treatment planning, the planning target volume (PTV) was defined as an enhanced lesion plus 3 mm margin. A total dose of 39-42 Gy in three fractions was delivered to the isocenters of the PTV. RESULTS: The median survival time after stereotactic radiotherapy was 17.4 months. The 1- and 2-year survival rates were 61% and 32%, respectively. The presence of extracranial tumors, the pre-treatment performance status, and the Radiation Therapy Oncology Group recursive partitioning analysis class were significant prognostic factors. The 1- and 2-year local recurrence rates were 14% and 17%, respectively, with no serious acute toxic effect. Injuries involving brain necrosis were observed in six patients. New brain metastases or meningeal carcinomatosis was seen in more than half of the patients following treatment with stereotactic radiotherapy. CONCLUSIONS: Hypofactionated stereotactic radiotherapy with mMLC is considered to be an effective and safe modality for the treatment of brain metastases in lung cancer patients.

High-dose-rate intracavitary brachytherapy combined with external beam radiotherapy for stage IIIb adenocarcinoma of the uterine cervix in Japan: a multi-institutional study of Japanese Society of Therapeutic Radiology and Oncology 2006-2007 (study of JASTRO 2006-2007).

OBJECTIVE: The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors. METHODS: Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED(10)) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy. RESULTS: The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED(10) <75 Gy, 24.7% for T-BED(10) between 75 and 100 Gy and 0% for T-BED(10) >110 Gy (P = 0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P = 0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P = 0.96). CONCLUSIONS: The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED(10) and evident prognostic factors were not clear from this questionnaire survey.

Quality assurance in the prospective multi-institutional trial on definitive radiotherapy using high-dose-rate intracavitary brachytherapy for uterine cervical cancer: the individual case review.

OBJECTIVE: To assess compliance with the radiotherapy protocol of a multi-institutional prospective study (JAROG0401/JROSG04-2), which investigated the efficacy and toxicity of definitive radiotherapy using high-dose-rate intracavitary brachytherapy (HDR-ICBT) for early-stage uterine cervical cancer patients. METHODS: Individual case reviews (ICRs) were performed on all 60 study participants. Radiotherapy data were submitted to the quality assurance (QA) committee, which performed ICRs on 16 QA items according to previously selected criteria. The items focused on quality of external beam radiotherapy (EBRT), HDR-ICBT and both. Each item was determined to be either acceptable or a deviation. The QA committee performed ICR three times as planned, two during the patient accrual and the final one just after the final patient accrued. The QA results of the first and second reviews were reported back to the investigators after each ICR. RESULTS: In 40 cases (67%), all 16 QA items were classified as acceptable. One deviation was found in 16 cases, two deviations were identified in 3 cases and three deviations were noted in 1 case. The most frequently observed deviation was missing the rules for determining point A (10 cases). The items described by quantitative values, such as prescribed doses, certain time intervals and overall treatment time, were well followed. The proportion of deviations gradually decreased during the ICR process. CONCLUSIONS: The present ICR demonstrated the favorable radiotherapy compliance with the JAROG0401/JROSG04-2 protocol. The QA process using ICRs can potentially be used to improve the quality of radiotherapy, including HDR-ICBT in the multi-institutional prospective studies for cervical cancer.

High dose-rate intracavitary brachytherapy for cervical carcinomas with lower vaginal infiltration.

PURPOSE: This report presents the clinical applications of an automated treatment-planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for advanced uterine cervical cancer infiltrating the parametrium and the lower vagina. METHODS AND MATERIALS: We adopted HDR-ICBT under optimized dose distribution for 22 cervical cancer patients with tumor infiltration of the lower half of the vagina. All patients had squamous cell carcinoma with International Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional ICBT was applied as "pear-shaped" isodose curve. Then 3-4 more sessions per week of this new method of ICBT were performed. With a simple determination of the treatment volume, the cervix-parametrium, and the lower vagina were covered automatically and simultaneously by this program, that was designated as "utero-vaginal brachytherapy". The mean follow-up period was 87.4 months (range, 51.8-147.9 months). RESULTS: Isodose curve for this program was "galaxy-shaped". Five-year local-progression-free survival and overall survival rates were 90.7% and 81.8%, respectively. Among those patients with late complications higher than Grade 2 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis. CONCLUSIONS: Because of the favorable treatment outcomes, this treatment-planning program with a simplified target-volume based dosimetry was proposed for cervical cancer with lower vaginal infiltration.

Recommendations for high-risk clinical target volume definition with computed tomography for three-dimensional image-guided brachytherapy in cervical cancer patients.

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.

Radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma: long-term outcomes over 10 years.

This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31-84). Fifteen patients were Helicobacter pylori-negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30-39.5 Gy). The median follow-up period was 121 months (range: 8-176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases.

Multi-institutional study of radiation therapy for isolated para-aortic lymph node recurrence in uterine cervical carcinoma: 84 subjects of a population of more than 5,000.

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 > or =51 Gy and that of < or =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.

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study.

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2-135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.

Phase II study of bi-weekly docetaxel and carboplatin with concurrent thoracic radiation therapy followed by consolidation chemotherapy with docetaxel plus carboplatin for stage III unresectable non-small cell lung cancer.

OBJECTIVE: Docetaxel and carboplatin (DC) have demonstrated activity as radiation sensitizers in pre-clinical studies. The aim of this phase II study was to evaluate the efficacy and toxicity of DC with concurrent thoracic radiation therapy (TRT) followed by consolidation chemotherapy with DC for stage III unresectable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty-three previously untreated patients with inoperable, locally advanced (LA) NSCLC received docetaxel 30 mg/m2 over 1 h and carboplatin at an AUC of 3 every 2 weeks for six courses--four courses during concurrent chemoradiotherapy and two courses following completion of radiotherapy. Concurrent TRT was performed in 2-Gy daily fractions to a total dose of 60 Gy. RESULTS: Among 32 evaluable patients, the overall response rate was 91%, with two complete responses (CR) and 27 partial responses (PR). Median survival time by intention-to-treat analysis was 27 months, with survival rates of 76% at 1 year and 61% at 2 years. Serious side effects were generally limited to grade 3 neutropenia in 6%, grades 3 and 4 pulmonary toxicity in 6 and 3%, respectively, and grade 3 esophagitis in 3% of patients. CONCLUSIONS: DC with concurrent TRT followed by consolidation chemotherapy was highly active with manageable toxicity in patients with stage III unresectable NSCLC.

Concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin for stage III unresectable, non-small-cell lung cancer: clinical application of a protocol used in a previous phase II study.

PURPOSE: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m(2), and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy. RESULTS: The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade ≥3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade ≥3 severity were observed in 2.6% and 1.7% of patients, respectively. CONCLUSIONS: The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.

Insufficiency fractures after pelvic radiation therapy for uterine cervical cancer: an analysis of subjects in a prospective multi-institutional trial, and cooperative study of the Japan Radiation Oncology Group (JAROG) and Japanese Radiation Oncology Study Group (JROSG).

PURPOSE: To investigate pelvic insufficiency fractures (IF) after definitive pelvic radiation therapy for early-stage uterine cervical cancer, by analyzing subjects of a prospective, multi-institutional study. MATERIALS AND METHODS: Between September 2004 and July 2007, 59 eligible patients were analyzed. The median age was 73 years (range, 37-84 years). The International Federation of Gynecologic Oncology and Obstetrics stages were Ib1 in 35, IIa in 12, and IIb in 12 patients. Patients were treated with the constant method, which consisted of whole-pelvic external-beam radiation therapy of 50 Gy/25 fractions and high-dose-rate intracavitary brachytherapy of 24 Gy/4 fractions without chemotherapy. After radiation therapy the patients were evaluated by both pelvic CT and pelvic MRI at 3, 6, 12, 18, and 24 months. Diagnosis of IF was made when the patients had both CT and MRI findings, neither recurrent tumor lesions nor traumatic histories. The CT findings of IF were defined as fracture lines or sclerotic linear changes in the bones, and MRI findings of IF were defined as signal intensity changes in the bones, both on T1- and T2-weighted images. RESULTS: The median follow-up was 24 months. The 2-year pelvic IF cumulative occurrence rate was 36.9% (21 patients). Using Common Terminology Criteria for Adverse Events version 3.0, grade 1, 2, and 3 IF were seen in 12 (21%), 6 (10%), and 3 patients (5%), respectively. Sixteen patients had multiple fractures, so IF were identified at 44 sites. The pelvic IF were frequently seen at the sacroileal joints (32 sites, 72%). Nine patients complained of pain. All patients' pains were palliated by rest or non-narcotic analgesic drugs. Higher age (>70 years) and low body weight (<50 kg) were thought to be risk factors for pelvic IF (P=.007 and P=.013, Cox hazard test). CONCLUSIONS: Cervical cancer patients with higher age and low body weight may be at some risk for the development of pelvic IF after pelvic radiation therapy.

Prospective multi-institutional study of definitive radiotherapy with high-dose-rate intracavitary brachytherapy in patients with nonbulky (<4-cm) stage I and II uterine cervical cancer (JAROG0401/JROSG04-2).

PURPOSE: 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. METHODS AND MATERIALS: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 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/ß = 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. RESULTS: 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. CONCLUSIONS: 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.

Intraoperative radiotherapy for unresectable pancreatic cancer: a multi-institutional retrospective analysis of 144 patients.

PURPOSE: To retrospectively analyze the results of intraoperative radiotherapy (IORT) + external beam radiotherapy (EBRT) for unresectable pancreatic cancer. METHODS AND MATERIALS: The records of 144 patients treated with IORT, with or without, EBRT were reviewed. One hundred and thirteen patients (78.5%) were treated with IORT + EBRT and 114 patients (79.2%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy and 45 Gy, respectively. The median follow-up of all 144 patients was 9.6 months (range, 0.5-69.7 months). RESULTS: At the time of this analysis, 131 of 144 patients (91.0%) had disease recurrences. Local progression was observed in 60 patients (41.7%), and the 2-year local control (LC) rate in all patients was 44.6%. Patients treated with IORT, with or without, EBRT had significantly more favorable LC (2-year LC, 50.9%) than those treated with IORT without EBRT (p = 0.0004). The 2-year overall survival (OS) rate and the median survival time in all 144 patients were 14.7% and 10.5 months, respectively. Patients treated with chemotherapy had a significantly favorable OS than those treated without chemotherapy (p < 0.0001). On univariate analysis, chemotherapy use alone had a significant impact on OS and on multivariate analysis; chemotherapy use was a significant prognostic factor. Late gastrointestinal morbidity of National Cancer Institute-Common Terminology Criteria Grade 3 was observed in 2 patients (1.4%). CONCLUSION: IORT + EBRT yields a relatively favorable LC rate for unresectable pancreatic cancer with low frequency of severe late toxicity, and IORT combined with chemotherapy conferred a survival benefit compared with IORT without chemotherapy.

Intraoperative radiotherapy for resected pancreatic cancer: a multi-institutional retrospective analysis of 210 patients.

PURPOSE: To retrospectively analyze the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (EBRT) for resected pancreatic cancer. METHODS AND MATERIALS: The records of 210 patients treated with gross complete resection (R0: 147 patients; R1: 63 patients) and IORT with or without EBRT were reviewed. One hundred forty-seven patients (70.0%) were treated without EBRT and 114 patients (54.3%) were treated in conjunction with chemotherapy. The median doses of IORT and EBRT were 25 Gy (range, 20-30 Gy) and 45 Gy (range, 20-60Gy), respectively. The median follow-up of the surviving 62 patients was 26.3 months (range, 2.7-90.5 months). RESULTS: At the time of this analysis, 150 of 210 patients (71.4%) had disease recurrences. Local failure was observed in 31 patients (14.8%), and the 2-year local control rate in all patients was 83.7%. The median survival time and the 2-year actuarial overall survival (OS) in all 210 patients were 19.1 months and 42.1%, respectively. Patients treated with IORT and chemotherapy had a significantly more favorable OS than those treated with IORT alone (p = 0.0011). On univariate analysis, chemotherapy use, degree of resection, carbohydrate antigen 19-9, and pathological N stage had a significant impact on OS and on multivariate analysis; these four factors were significant prognostic factors. Late gastrointestinal morbidity of NCI-CTC Grade 4 was observed in 7 patients (3.3%). CONCLUSION: IORT yields an excellent local control rate for resected pancreatic cancer with few frequencies of severe late toxicity, and IORT combined with chemotherapy confers a survival benefit compared with that of IORT alone.

Axillary lymph node dissection can be avoided in women with breast cancer with intraoperative, false-negative sentinel lymph node biopsies.

BACKGROUND: It is currently unclear which patients with breast cancer with sentinel lymph node (SLN) metastases do not need axillary lymph node dissection (ALND). PATIENTS AND METHODS: A cohort of 1,132 women who had unilateral invasive breast cancer with clinically negative nodes or nodes suspicious for metastasis, were intraoperatively diagnosed as having negative SLNs, and did not undergo an immediate ALND. Our intraoperative histological investigation uses H&E staining of a frozen section from a maximum cut surface of each SLN. Of these 1,132 women, 132 (11.7%) were postoperatively diagnosed as having positive SLNs, which classifies them as having an intraoperative, false-negative SLN biopsy (SLNB). Patient and tumor characteristics, treatment methods, and the prognoses of these patients were investigated and compared with the remaining 1,000 patients who were negative for SLNB. RESULTS: Of the 132 patients with intraoperative, false-negative SLNB, none underwent a further ALND. With a median follow-up period of 58.1 months, none of these patients exhibited recurrence in the axillary nodes. Their recurrence-free survival rates were not statistically different from those of patients with negative SLNB. CONCLUSIONS: ALND can be avoided in most patients with breast cancer with intraoperative, false-negative SLNB.