Chikako Yamauchi

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/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. 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.

Concurrent chemoradiotherapy for esophageal cancer: comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil

BackgroundAlthough current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation.MethodsConcurrent chemoradiotherapy, using 60 Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001.ResultsComplete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group.ConclusionCLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information.

Measuring Quality of Life in Patients with Breast Cancer: A Systematic Review of Reliable and Valid Instruments Available in Japan

BackgroundLittle is known about the availability and psychometric properties of instruments to measure quality of life (QOL) in clinical research on Japanese patients with breast cancer. The purpose of this systematic review is to find reliable and valid instruments available in Japan, and to summarize their characteristics.MethodsInstruments available in Japan were found through a systematic search of the literature. Each instrument identified was evaluated for item development, reliability, validity, interpretability and utility.ResultsSix questionnaires to measure health-related QOL (the QOL-ACD, the EORTC QLQ-C30, the EORTC QLQ-BR23, the FACT-B, the SF-36, the WHO/QOL-26) and five scales to quantify the psychological burden (the STAI, the POMS, the SDS, the HADS, the GHQ), for which reliability and validity have been documented, are available in Japanese. All instruments were developed in foreign countries except for the QOL-ACD. Two of the QOL questionnaires were specific to breast cancer (the EORTC QLQ-BR23, the FACT-B). Though the measurements can be interpreted in some manner, the meaning of change scores over time has been documented for only three instruments (the EORTC QLQ-C30, the FACT-B, and the GHQ).ConclusionsThe review provides grounds for designing and implementing quantitative research on QOL of breast cancer patients in Japan. Methodological challenges, however, continue, particularly for validating instruments with regard to various study populations of Japanese people and demonstrating the clinical importance of change scores.

Radiation Therapy for Brain Metastases from Breast Cancer

BackgroundBreast cancer is one of the most common malignancies that metastasize to the brain. Radiation therapy plays a central role in the management of brain metastases.MethodsThe medical records of 36 patients with brain metastases from breast cancer who underwent whole-brain radiation therapy (WBRT) at Kyoto University Hospital between 1993 and 2001 were reviewed. The treatment outcomes were analyzed retrospectively.ResultsThe median age at the time of diagnosis of brain metastases was 52 years. Only 4 patients (11%) had a single metastasis, while the others had multiple metastases. Uncontrolled extracranial metastases were present in 26 patients at the time of diagnosis of brain metastases. All patients received WBRT at a median dose of 31 Gy. Eight patients received conventional external-beam boost irradiation, and 2 received boost stereotactic radiosurgery (SRS). The overall median survival time was 7.9 months. Uncontrolled extracranial metastases except for bone metastases and old age were significantly associated with a poor survival rate. Twenty-six patients (82%) showed initial response, but 15 developed CNS failure, including 9 patients whose tumor recurred at the original site, 4 patients who developed tumors elsewhere in the brain and 3 patients who exhibited meningeal spread. The median duration of intracranial failure was 5.0 months. Whole-brain dose, and total tumor dose did not affect intracranial control.ConclusionsRadiation therapy yielded a high initial response, but the duration of effect was limited with external beam irradiation alone. New treatment strategies such as adding SRS need to be studied further.

Avascular necrosis of bilateral femoral head as a result of long-term steroid administration for radiation pneumonitis after tangential irradiation of the breast

We report a patient with avascular necrosis of the bilateral femoral head resulting from long-term steroid administration for radiation pneumonitis that occurred after tangential irradiation of the breast. The patient was a 50-year-old postmenopausal woman with breast cancer, stage IIIB (T4bN0M0) in the right C area. Following wide excision of right breast carcinoma and level III axillary lymph node dissection, whole-breast X-ray irradiation was given, at a dose of 2 Gy per fraction; the total dose was 50 Gy. On day 84 after the initiation of radiation therapy, she developed radiation pneumonitis. As the lung shadow expanded to the contralateral lung, she received steroid medication. Despite the steroid medication, the symptoms were exacerbated; therefore, she underwent steroid pulse administration with subsequent oral steroid medication. She improved immediately, but subsequently the radiation pneumonitis relapsed three times when the steroid medication was stopped. The period of medication was 423 days and the cumulative amount of steroids was 7365 mg before complete resolution occurred. In the 19 months after she stopped the steroid administration, she developed avascular necrosis (AVN) of the bilateral femoral head. This was regarded as a complication of the steroid treatment. Patients treated with long-term or high-dose steroid administration have been suggested to be at great risk of developing AVN, but this hypothesis remains controversial. The probability of AVN occurrence may be very small, but it should be considered as one of the complications of steroids, which are often used to treat radiation pneumonitis.

Systematic Overview of Quality of Life Studies for Breast Cancer

BackgroundThe concept of quality of life (QOL) is essentially subjective, determined from the patient’s point of view. Thus, an appropriate investigation and analysis of QOL as an indicator of medical treatment outcome is a task of some difficulty. The physician-led QOL assessment studies to date in Japan have suffered from insufficient knowledge and understanding of the diverse factors contributing to QOL, thereby contributing to a dearth of quality studies. Given this background, the Japanese Breast Cancer Society has established a Task Force for the development of guidelines to properly conduct QOL assessment studies. The present article reports the results of a large-scale systematic overview of QOL assessment studies for breast cancer patients that was undertaken as one part of this project.MethodsSix databases were used in this overview: MEDLINE, CINAHL, CANCERLIT, EMBASE, PsychINFO, and Japan Centra Revuo Medicina. The search period was 1982-1999 for CINAHL, and 1990-1999 for the others. Following a check of the titles, important information was recorded on relevance and data collection forms.ResultsA systematic search was conducted of the literature on QOL assessment studies for breast cancer patients, and 1,954 articles were extracted from a check of titles. Using the relevance and data collection forms, the number of articles was further narrowed to 126. These articles were then classified according to the type and design of the study, the number of QOL and psychological measures used, frequency of use of each measure, and study focus and type of intervention. The results were then compiled.ConclusionTo date there have been almost no appropriate systematic overviews or guidelines issued for QOL assessment studies related to breast cancer, even on the international level. The results of the present study may contribute high-quality QOL information for evidence-based medicine, as it continues to gain global prevalence.

Late skin and subcutaneous soft tissue changes after 10-gy boost for breast conserving therapy.

PurposeTo evaluate the influence of boost irradiation for breast conserving therapy on skin and subcutaneous tissue.Materials and MethodsBetween 1989 and 1995, 468 patients were treated with breast conserving surgery (quadrantectomy or wide excision with axillary dissection) followed by 50 Gy whole breast irradiation. Among them, fifty-eight patients with positive or close margins were treated with 10 Gy external beam boost irradiation. Skin and subcutaneous soft tissue changes during 5-years of follow-up were examined by inspection and palpation and evaluated using the BCT follow-up form based on EORTC late effect toxicity scoring.ResultFour percent (20/468) of the patients showed grade 2 late changes in skin and soft tissue. Four of them had skin telangiectasis, which was limited to within the boost field. Boost irradiation had no definite influence on other late changes. Patients’ age, extent of surgery, and pT size had no significant relation to the late changes. The cosmetic score 5 years after BCT was not significantly different between the patients with and without boost irradiation.ConclusionAlthough 10 Gy boost irradioation after 50 Gy whole breast irradiation increased skin telangiectasis, the late skin and soft tissue changes caused by the boost irradiation were generally mild and there was no substantial deterioration of cosmetic outcome.

Feasibility of accelerated partial breast irradiation using three-dimensional conformal radiation therapy for Japanese women: a theoretical plan using six patients’ CT data

BackgroundSeveral methods have been reported for accelerated partial breast irradiation (APBI), but in Japan, there are few facilities where brachytherapy or intra-operative radiotherapy is available. Japanese women have smaller physiques than American women in general. Thus, we developed external beam plans for APBI using computed tomography (CT) data of Japanese patients, to investigate whether APBI using three-dimensional conformal radiation therapy is safely applicable for Japanese women, while verifying the dose distributions.MethodsWe used CT data from six Japanese patients with early breast cancer, which were obtained in routine clinical practice during whole breast irradiation (WBI) after wide excision, and made 32 APBI plans according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 and the Radiation Therapy Oncology Group (RTOG) 0413 protocol, which compared APBI with WBI. We then investigated the compliance to the dose constraints of the protocol.Results None of 16 plans for the medial regions met the dose constraints regardless of laterality of the breast. The major reason was overdosage to the contralateral breast. Thirteen of 16 plans (81%) for the lateral regions met the dose constraints. The remaining three plans (19%) did not meet the dose limitation of the uninvolved normal breast, suggesting that a large ratio of the target to the breast was problematic.Conclusions In Japanese women, patients with a laterally located small tumor can be candidates for APBI using three-dimensional conformal radiation therapy.

Japanese Structure Survey of High-precision Radiotherapy in 2012 Based on Institutional Questionnaire about the Patterns of Care

OBJECTIVE The purpose of this study was to clarify operational situations, treatment planning and processes, quality assurance and quality control with relevance to stereotactic radiotherapy, intensity-modulated radiotherapy and image-guided radiotherapy in Japan. METHODS We adopted 109 items as the quality indicators of high-precision radiotherapy to prepare a questionnaire. In April 2012, we started to publicly open the questionnaire on the website, requesting every institution with radiotherapy machines for response. The response ratio was 62.1% (490 out of 789 institutions responded). RESULTS Two or more radiotherapy technologists per linear accelerator managed linear accelerator operation in ∼90% of the responded institutions while medical physicists/radiotherapy quality managers were engaged in the operation in only 64.9% of the institutions. Radiotherapy certified nurses also worked in only 18.4% of the institutions. The ratios of the institutions equipped for stereotactic radiotherapy of lung tumor, intensity-modulated radiotherapy and image-guided radiotherapy were 43.3, 32.6 and 46.8%, respectively. In intensity-modulated radiotherapy planning, radiation oncologists were usually responsible for delineation while medical physicists/radiotherapy quality managers or radiotherapy technologists set up beam in 33.3% of the institutions. The median time required for quality assurance of intensity-modulated radiotherapy at any site of brain, head and neck and prostate was 4 h. Intensity-modulated radiotherapy quality assurance activity had to be started after clinical hours in >60% of the institutions. CONCLUSIONS This study clarified one major issue in the current high-precision radiotherapy in Japan. A manpower shortage should be corrected for high-precision radiotherapy, especially in the area relevant to quality assurance/quality control.

Personalization of loco-regional care for primary breast cancer patients (part 2)

Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.