Daisaku Yoshida

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.

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/m2 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.

A seven-year disease-free survivor of malignant pleural mesothelioma treated with hyperthermia and chemotherapy: a case report

IntroductionMalignant pleural mesothelioma was once a rare finding but its incidence is increasing worldwide, most likely because of widespread exposure to asbestos. Although complete surgical resection is considered the only curative treatment, the results of surgery have shown a median survival time of only one year. In inoperable cases, chemotherapy, radiotherapy, and a combination of both have been considered as palliative therapy. Therefore, outcomes for inoperable cases have been poor. Here, we report the case of a long-term survivor treated with hyperthermia and chemotherapy.Case presentationA 61-year-old Japanese man with a performance status of 1 due to chest pain was referred to our hospital. He had a history of asbestos exposure for approximately five years. A computed tomography scan showed diffuse extensive right pleural thickening with small nodular lesions, and video-assisted thoracoscopy revealed tumor invasion of the ipsilateral chest wall muscles. The histopathologic findings were consistent with a diagnosis of malignant pleural mesothelioma (sarcomatoid type). The tumor was diagnosed as being stage cT3N0M0. Our patient refused any invasive therapies including surgery and radiotherapy, and was therefore treated with hyperthermia and systemic chemotherapy with agents such as cisplatin and irinotecan. He underwent three hyperthermia sessions and a single course of chemotherapy without any severe complications. One month after treatment, a follow-up computed tomography scan showed no definitive abnormality in the thoracic space. Our patient has subsequently survived without any evident disease for more than seven years.ConclusionsThe combination of hyperthermia and chemotherapy may be a novel and safe therapeutic option for malignant pleural mesothelioma, and can be considered for patients ineligible for radical treatment. Further clinical studies of the combination of hyperthermia and chemotherapy are needed to confirm the effects of this treatment on malignant pleural mesothelioma.

Inoperable Pancoast tumors treated with hyperthermia-inclusive multimodality therapies

PURPOSE This study aimed to assess the feasibility, efficacy and complication of hyperthermia-inclusive multimodality therapies for patient with inoperable Pancoast tumor. MATERIAL AND METHODS Five patients with inoperable Pancoast tumor were treated with hyperthermia-inclusive multimodality therapies. They received thermoradiotherapy with/without chemotherapy. Radiation therapy was delivered using 10 MV X-rays with total dose of 68-70 Gy. In the latter half of the radiation therapy hyperthermia was performed for 2-4 sessions once a week with 8 MHz radiofrequency device. RESULTS For primary response, 4 tumors showed partial response to the treatment with the exception of 1 tumor who showed stable disease. Only one patient was with a short follow-up period (9 months), all other patients survived 3 years or more without recurrence. Of them, 2 patients were recognized with local recurrence at 38.7 and 42.7 months after treatment and died at 66.9 and 78.5 months after treatment. The other 2 patients are disease-free survivor for 4 and 5 years after treatment. No severe non-hematological toxicity was observed in each patient. CONCLUSION These data suggested that hyperthermia-inclusive multimodality therapies might be a promising approach for inoperable Pancoast tumor.

A surveillance study of intensity-modulated radiation therapy for postoperative cervical cancer in Japan

Intensity-modulated radiation therapy (IMRT) was recently introduced to the field of gynecologic malignancies; however, its value is not yet validated. A clinical trial is in preparation to investigate the efficacy and feasibility of IMRT for postoperative cervical cancer. The object of this study was to perform a surveillance study of IMRT for post-operative cervical cancer. A questionnaire regarding the precise methods of conducting IMRT was sent to six institutions that had already introduced IMRT for post-operative cervical cancer, and the data were analyzed. Half of the institutions used static IMRT and the others used volumetric-modulated arc therapy (VMAT). Most institutions used body-immobilizing devices for patient fixation. Most institutions instructed patients to fill their bladder before undergoing planning CT or daily treatment. While one institution inserted metallic markers and another one used radio-contrast–soaked gauze to visualize the vaginal cuff, the other institutions used nothing for vaginal cuff visualization. Most institutions defined the clinical target volumes according to the Japan Clinical Oncology Group or the Radiation Therapy Oncology Group guidelines. Only one institution used a prescribed dose based on 95% of the PTV (D95), while the rest used the mean dose (Dmean). This valuable information from six leading institutions will be utilized in a future prospective clinical trial.

Patterns of practice in the radiation therapy for bladder cancer: survey of the Japanese Radiation Oncology Study Group (JROSG).

OBJECTIVE To retrospectively analyze the clinical outcomes of radiation therapy with or without chemotherapy for bladder cancer in Japan. METHODS A questionnaire-based survey of patients with pathologically proven bladder cancer treated by definitive radiation therapy between 2002 and 2006 was conducted by the Japanese Radiation Oncology Study Group, and the clinical records of 159 patients were collected from 17 institutions. Concurrent intra-arterial chemoradiotherapy and concurrent systemic chemoradiotherapy were administered in 51 and 33 patients, respectively. RESULTS The 5-year overall survival and bladder preservation rates were 48 and 39%, respectively. Eighty-nine (56%) patients developed recurrence (bladder, 48; regional lymph nodes, 4; distant sites, 41). The results of multivariate analysis revealed that adoption of chemotherapy was the only significant prognostic factor for overall survival (relative risk = 0.615 [95% confidence interval: 0.439-0.862], P = 0.005). The type of chemotherapy administered did not significantly affect the local control or overall survival rates. The actuarial 5-year overall survival rates and bladder preservation in the radiation therapy combined with intra-arterial chemotherapy group were 64 and 58%, respectively, and the corresponding rates in the radiation therapy combined with systemic chemotherapy group were 67 and 42%, respectively. CONCLUSIONS The results of this survey revealed the current status of practice of radiation therapy for bladder cancer in Japan. A multi-institutional prospective study is needed based on the results of this study to determine the optimal radiotherapeutic approach, including the need for concurrent chemotherapy and the appropriate chemotherapy regimen for invasive bladder cancer.