Hitoshi Ikushima

Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma

PURPOSE To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. RESULTS Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. CONCLUSIONS FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.

The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma.

Background:To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib.Methods:Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients.Results:The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n=8; more than 50% reduction in volume) than in the low reduction rate group (n=9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland.Conclusion:Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells.

Radiation Therapy Definitions and Reporting Guidelines for Thymic Malignancies

The role of radiation therapy in the treatment of thymic malignancies is still being established, and many details that have never been clearly defined are currently being critically examined. Such an assessment has been hampered by significant inconsistency in how radiotherapy (RT) is delivered, how the RT field is defined, which patients are selected for treatment, and how outcomes are reported. An opportunity to change this has arisen through the development of the International Thymic Malignancy Interest Group (ITMIG), which is an organized collaboration of individuals interested in this field. The prerequisite to progress, however, is to establish definitions and consistent policies, so that results can be understood and compared. This is the topic addressed in this article.

Chemoradiation Therapy for Cervical Cancer : Toxicity of Concurrent Weekly Cisplatin

PurposeTo retrospectively evaluate the toxicity of concurrent weekly cisplatin and radiation therapy (RT) for locally advanced cervical cancer.Materials and MethodsBetween April 2001 and December 2004, 21 consecutive previously untreated patients with locally advanced cervical cancer were treated with concurrent chemoradiation therapy (CCRT) at the Tokushima University Hospital. Clinical stages were II: 5, III: 15, IVA: 1. External beam radiation therapy (EBRT) was delivered with 10 MV X-rays, 2 Gy fraction per day; total dose to the whole pelvis was 50 Gy. Iridium-192 high-doserate (HDR) intracavitary radiation therapy was performed with 10–30 Gy (median, 24 Gy) targeted at point A. Concurrent chemotherapy consisted of cisplatin, administered weekly at a dose of 40 mg/m2 for patients who were younger than 65 years and 30 mg/m2 for those 65 years or over. A maximum single dose of cisplatin, up to 70 mg/body, was administered in 5 cycles during EBRT.ResultsA total of 86 cycles of cisplatin were administered to the 21 patients, with a median of 4 cycles (range, 2–5). Severe hematological toxicity occurred in 18 patients (86%), including grade 3 in 17 patients (81%) and grade 4 in one patient (4.8%). Moderate or severe gastrointestinal toxicity occurred in 11 patients (52%), including grade 2 in 10 patients (48%) and grade 3 in one patient (4.8%). The grades of hematological toxicity were significantly greater in the 40 mg/m2 group than in the 30 mg/m2 group. All of the patients who were administered 40 mg/m2 of cisplatin developed grade 3 or greater hematological toxicity, including one patient with grade 4 toxicity. In the 30 mg/m2 group, 3 of 10 patients developed less than grade 3 toxicity, and all patients completed radiation therapy without interruption.ConclusionThe incidence of severe acute hematological toxicity was significantly higher in this study than in previously reported randomized controlled trials (RCTs), especially in the group of 40 mg/m2 cisplatin. A dose of 30 mg/m2 of cisplatin was considered to be feasible in weekly cisplatin and radiation therapy.

Daily alignment results of in-room computed tomography-guided stereotactic body radiation therapy for lung cancer

PURPOSE To determine the extent of interfractional setup errors and day-to-day organ motion errors by assessing daily bone alignment results and changes in soft tissue tumor position during hypofractionated, in-room computed tomography (CT)-guided stereotactic body radiation therapy (SBRT) of lung cancer. METHODS AND MATERIALS Daily alignment results during SBRT were analyzed for 117 tumors in 112 patients. Patients received 40-50 Gy of SBRT in four to five fractions using an integrated CT-LINAC system. The free-breathing CT scans acquired during treatment setup were retrospectively realigned to match with each of the bony references and the gross tumor volume (GTV) defined on the reference CT by rigid-body registration, and the daily deviations were calculated. RESULTS The mean magnitude (± SD) three-dimensional shift from the initial skin marks to the final bone-aligned positions was 9.4 ± 5.7 mm. The mean daily GTV deviation from the bone position was 0.1 ± 3.8 mm in the anterior-posterior direction, -0.01 ± 4.2 mm in the superior-inferior direction, and 0.2 ± 2.5 mm in the lateral direction. A clinically noteworthy trend (net change >5 mm in any direction) in GTV position relative to the bone was observed in 23 cases (20%). CONCLUSIONS Soft tissue target position can change significantly beyond the motion envelope defined in the original internal target volume in four-dimensional CT-based treatment planning for SBRT of lung cancer. Additional margin should be considered for adequate coverage of interfractional changes.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

BackgroundVulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.ObjectiveThe JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.MethodsThe guideline was created according to the basic principles in creating the guidelines of JSGO.ResultsThe guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.ConclusionOverall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

High-dose-rate brachytherapy for patients with maxillary gingival carcinoma using a novel customized intraoral mold technique

OBJECTIVE The purpose of this study was to introduce a novel customized intraoral mold treatment for maxillary gingival carcinoma (UGC). STUDY DESIGN Two patients with UGC were treated as salvage therapy using this technique. The mold was designed to keep normal soft tissues adjacent to the tumor away from the radioactive source as much as possible, and it was shielded by lead. The radiation dose on the buccal mucosa and tongue was measured at the inner and outer surfaces of the intraoral mold before starting high-dose-rate brachytherapy by the remote afterloading system, and was reduced to almost one tenth. RESULTS The patient had no recurrence and no severe adverse effects on the normal soft tissue adjacent to the tumor until the end of the follow-up period. CONCLUSION High-dose-rate brachytherapy using the novel customized intraoral mold might be a treatment option of not only salvage therapy, but definitive therapy of UGC.

Effective bladder preservation strategy with low-dose radiation therapy and concurrent intrarrterial chemotherapy for muscle-invasive bladder cancer

PurposeThe aim of this study was to evaluate retrospectively the toxicity and response, bladder preservation, and survival of patients with muscle-invasive bladder cancer treated with multimodality therapy consisting of low-dose radiation therapy (RT) and concurrent intraarterial chemotherapy (IACT).Methods and materialsBetween November 1999 and July 2005, a total of 27 consecutive, previously untreated patients with muscle-invasive bladder cancer underwent transurethral bladder tumor resection followed by concurrent low-dose RT and IACT. Patients who achieved a complete response (CR) were followed up closely without further therapy, and patients who did not achieve a CR underwent further treatment.ResultsComplete response was achieved in 22 of 27 patients (81%). Of these 22 patients, 7 developed recurrences, and 3 died of their disease. In five patients who did not achieve CR, one died from bone metastases. The 3-year overall survival rate was 81%, with a median follow-up time of 27 months; and 22 of 27 patients (81%) with a preserved bladder were tumor-free at the last follow-up. Three patients (11%) developed grade 3 acute hematological toxicity.ConclusionMultimodality therapy consisting of low-dose RT and concurrent IACT for muscle-invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation and minimal adverse effects.

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.

Reirradiation of paraaortic lymph node metastasis by brachytherapy with hyaluronate injection via paravertebral approach: With DVH comparison to IMRT

UNLABELLED PURPOSE/INTRODUCTION: To safely irradiate retroperitoneal targets as paraaortic lymph node by separating abdominal at-risk organs from the target during irradiation, we created a percutaneous paravertebral approach of high-dose-rate brachytherapy with hyaluronate gel injection (HGI). We report a case treated with this technique. METHODS AND MATERIALS We encountered a patient with symptomatic regrowth of paraaortic lymph node metastasis from prostatic cancer. He had previously received 58.4Gy of radiotherapy to the same region 12 months prior. Brachytherapy needles and a HGI needle were deployed via the paravertebral approach under local anesthesia at our outpatient clinic. RESULTS A single dose of 22.5Gy (equivalent to 60.94Gy in 2Gy per fraction schedule calculated at α/β=10) was delivered to the target, with preservation of the surrounding small intestine by HGI with D(2cc) (minimum dose to the most irradiated volume of 2mL) of 5.05Gy. Therapeutic ratio was 3.64 times higher for this brachytherapy plan compared with an intensity-modulated radiation therapy plan. At followup at 1 year after brachytherapy, the symptoms had disappeared, tumor size had reduced with no fluorodeoxyglucose accumulation, and prostate-specific antigen level had decreased. CONCLUSION We consider that high-dose-rate brachytherapy with the HGI procedure offers effective treatment even in this type of reirradiation situation.