Yuko Kaneyasu

A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer

OBJECTIVE To develop a consensus-based guideline as well as an atlas defining pelvic nodal clinical target volumes in external beam radiotherapy for uterine cervical cancer. METHODS A working subgroup to establish the consensus-based guideline on clinical target volumes for uterine cervical cancer was formulated by the Radiation Therapy Study Group of the Japan Clinical Oncology Group in July 2008. The working subgroup consisted of seven radiation oncologists. The process resulting in the consensus included a comparison of contouring on CT images among the members, reviewing of published textbooks and the relevant literature and a distribution analysis of metastatic nodes on computed tomography/magnetic resonance imaging of actual patients. RESULTS The working subgroup defined the pelvic nodal clinical target volumes for cervical cancer and developed an associated atlas. As a basic criterion, the lymph node clinical target volume was defined as the area encompassed by a 7 mm margin around the applicable pelvic vessels. Modifications were made in each nodal area to cover adjacent adipose tissues at risk of microscopic nodal metastases. Although the bones and muscles were excluded, the bowel was not routinely excluded in the definition. Each of the following pelvic node regions was defined: common iliac, external iliac, internal iliac, obturator and presacral. Anatomical structures bordering each lymph node region were defined for six directions; anterior, posterior, lateral, medial, cranial and caudal. Drafts of the definition and the atlas were reviewed by members of the JCOG Gynecologic Cancer Study Group (GCSG). CONCLUSIONS We developed a consensus-based guideline defining the pelvic node clinical target volumes that included an atlas. The guideline will be continuously updated to reflect the ongoing changes in the field.

IL12RB2 and ABCA1 Genes Are Associated with Susceptibility to Radiation Dermatitis

Purpose: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patients susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. Experimental Design: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of ≥2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. Results: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. Conclusion: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.

A Consensus-based Guideline Defining Clinical Target Volume for Primary Disease in External Beam Radiotherapy for Intact Uterine Cervical Cancer

OBJECTIVE To develop a consensus-based guideline to define clinical target volume for primary disease (clinical target volume primary) in external beam radiotherapy for intact uterine cervical cancer. METHODS The working subgroup of the JCOG Radiation Therapy Study Group began developing a guideline for primary clinical target volume in November 2009. The group consisted of 10 radiation oncologists and 2 gynecologic oncologists. The process started with comparing the contouring on computed tomographic images of actual cervical cancer cases among the members. This was followed by a comprehensive literature review that included primary research articles and textbooks as well as information on surgical procedures. Extensive discussion occurred in face-to-face meetings (three occasions) and frequent e-mail communications until a consensus was reached. RESULTS The working subgroup reached a consensus on the definition for the clinical target volume primary. The clinical target volume primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and ovaries. Definitions for these component structures were determined. Anatomical boundaries in all directions were defined for the parametrium. Examples delineating these boundaries were prepared for the posterior border of the parametrium for various clinical situations (i.e. central tumor bulk, degree of parametrial involvement). CONCLUSIONS A consensus-based guideline defining the clinical target volume primary was developed for external beam radiotherapy for intact uterine cervical cancer. This guideline will serve as a template for radiotherapy protocols in future clinical trials. It may also be used in actual clinical practice in the setting of highly precise external beam radiotherapy, including intensity-modulated radiotherapy.

Radiotherapy for superficial esophageal cancer

PURPOSE The results of definitive radiotherapy for superficial esophageal cancer is presented. METHODS AND MATERIALS Twenty-one patients with superficial squamous cell carcinoma of the esophagus were treated by definitive radiotherapy with megavoltage x-rays in Tokyo Womens Medical College from 1975 to December 1990. Eight patients refused surgery and 13 patients were considered to be unsuitable for surgery due to advanced age or morbid conditions such as severe pulmonary dysfunction, myocardial infarction, liver cirrhosis, and other cancer. Radiotherapy was performed using 1.8-2.2 Gy fraction dose, 5 times a week and with a total dose of 50-76 Gy/5-7 weeks (median; 70 Gy). Three patients received intraluminal radiotherapy in addition. Combined chemotherapy was performed in four cases, and three cases received it before radiotherapy and one case after radiotherapy. RESULTS Overall survival rate was 40.8%, and the cause-specific 5-year survival rate was 61.7%. The 5-year survival rate of the group with morbid conditions was 17.5%, but that of the group without morbid conditions was 60.6%. Seven patients developed recurrence (primary site: 3, lymph nodes: 3, lung: 1) and one patient revealed multicentric cancer of the hypopharynx with wide submucosal spread of the esophagus at 28 months after radiotherapy. No patient developed severe side effect due to radiotherapy. CONCLUSION Definitive radiotherapy with or without chemotherapy can be applied as an alternative therapy to surgery for superficial esophageal cancer, even for the operable patients under good general condition.

Functional Image-Guided Radiotherapy Planning in Respiratory-Gated Intensity-Modulated Radiotherapy for Lung Cancer Patients With Chronic Obstructive Pulmonary Disease

PURPOSE To investigate the incorporation of functional lung image-derived low attenuation area (LAA) based on four-dimensional computed tomography (4D-CT) into respiratory-gated intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) in treatment planning for lung cancer patients with chronic obstructive pulmonary disease (COPD). METHODS AND MATERIALS Eight lung cancer patients with COPD were the subjects of this study. LAA was generated from 4D-CT data sets according to CT values of less than than -860 Hounsfield units (HU) as a threshold. The functional lung image was defined as the area where LAA was excluded from the image of the total lung. Two respiratory-gated radiotherapy plans (70 Gy/35 fractions) were designed and compared in each patient as follows: Plan A was an anatomical IMRT or VMAT plan based on the total lung; Plan F was a functional IMRT or VMAT plan based on the functional lung. Dosimetric parameters (percentage of total lung volume irradiated with ≥20 Gy [V20], and mean dose of total lung [MLD]) of the two plans were compared. RESULTS V20 was lower in Plan F than in Plan A (mean 1.5%, p = 0.025 in IMRT, mean 1.6%, p = 0.044 in VMAT) achieved by a reduction in MLD (mean 0.23 Gy, p = 0.083 in IMRT, mean 0.5 Gy, p = 0.042 in VMAT). No differences were noted in target volume coverage and organ-at-risk doses. CONCLUSIONS Functional IGRT planning based on LAA in respiratory-guided IMRT or VMAT appears to be effective in preserving a functional lung in lung cancer patients with COPD.

Evaluation of the basic properties of the BANGkit? gel dosimeter

We evaluated the basic properties of a commercially available BANGkit gel dosimeter, which is a normoxic type of BANG gel. This gel-kit has the same composition as the BANG 3 gel, but is fully oxygenated. To exclude oxygen, oxygen scavenging ascorbic acid and copper sulfate as a catalyst are used. The properties that we examined are the effects of the concentrations of copper sulfate and ascorbic acid on the response, the reproducibility, the long-term stability, the temperature effect at irradiation and the dose-rate effect. In our results, the excellent linear fit of the R2-dose response in a dose range for clinical use and its reproducibility were observed. The precision of a linear fit was preserved for about 3 weeks. The temperature at irradiation showed a significant effect on the dose response. Although the dose-rate dependence in the high-dose range was observed, it was negligible for the clinical dose range up to 270 cGy. In conclusion, this gel dosimeter is thought to be utilizable in clinical practice, while we have to pay attention to the temperature during the entire measurement processes, and additionally there is room for improvement in the linearity and the dose-rate dependence in the high-dose range.

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer.

BackgroundThe indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy.MethodsBetween September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate ± seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60–66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml.ResultsThe median follow-up period after radiation therapy was 33 months (range, 12–98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients.ConclusionRadiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate ± seminal vesicles, to a total dose of 60–66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe.

Dynamic computed tomography appearance of tumor response after stereotactic body radiation therapy for hepatocellular carcinoma: How should we evaluate treatment effects?

To evaluate the dynamic computed tomography (CT) appearance of tumor response after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) and reconsider response evaluation criteria for SBRT that determine treatment outcomes.

Distribution patterns of metastatic pelvic lymph nodes assessed by CT/MRI in patients with uterine cervical cancer

BackgroundTo investigate the three-dimensional (3D) distribution patterns of clinically metastatic (positive) lymph nodes on pretreatment computed tomography (CT)/magnetic resonance imaging (MRI) images of patients with locally advanced cervical cancer.MethodsWe enrolled 114 patients with uterine cervical cancer with positive nodes by CT/MRI (≥10 mm in the shortest diameter). Pretreatment CT/MRI data were collected at 6 institutions. The FIGO stage was IB1 in 2 patients (2%), IB2 in 6 (5%), IIA in 3 (3%), IIB in 49 (43%), IIIB in 50 (44%), and IVA in 4 (4%) patients. The median cervical tumor diameter assessed by T2-weighted MRI was 55 mm (range, 10–87 mm). The anatomical distribution of the positive nodes was evaluated on CT/MRI images by two radiation oncologists and one diagnostic radiologist.ResultsIn these patients, 273 enlarged nodes were assessed as positive. The incidence of positive nodes was 104/114 (91%) for the obturator region, 31/114 (27%) for the external iliac region, 16/114 (14%) for the internal iliac region, 22/114 (19%) for the common iliac region, and 6/114 (5%) for the presacral region. The external iliac region was subdivided into four sub-regions: lateral, intermediate, medial, and caudal. The obturator region was subdivided into two sub-regions: cranial and caudal. The majority of patients had positive nodes in the cranial obturator and/or the medial external iliac region (111/114). In contrast, few had positive nodes in the lateral external iliac, caudal external iliac, caudal obturator, internal iliac and presacral regions. All cases with positive nodes in those low-risk regions also had positive nodes in other pelvic nodal regions concomitantly. The incidence of positive nodes in the low-risk regions/sub-regions was significantly related to FIGO stage (p=0.017) and number of positive nodes (p<0.001).ConclusionsWe demonstrated the 3D distribution patterns of clinical metastatic pelvic lymph nodes on pretreatment CT/MRI images of patients with locally advanced cervical cancer. These findings might contribute to future individualization of the clinical target volume of the pelvic nodes in patients with cervical cancer.

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

Abstract 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.