Kengo Himei

Frequency, outcome and prognostic factors of carotid blowout syndrome after hypofractionated re-irradiation of head and neck cancer using CyberKnife: A multi-institutional study

PURPOSE Re-irradiation has attracted attention as a potential therapy for recurrent head and neck tumors. However, carotid blowout syndrome (CBS) has become a serious complication of re-irradiation because of the associated life-threatening toxicity. Determining of the characteristics of CBS is important. We conducted a multi-institutional study. METHODS AND PATIENTS Head and neck carcinoma patients (n=381) were treated with 484 re-irradiation sessions at 7 Japanese CyberKnife institutions between 2000 and 2010. RESULTS Of these, 32 (8.4%) developed CBS, which proved fatal that median survival time after CBS onset was 0.1 month, and the 1-year survival rate was 37.5%. The median duration between re-irradiation and CBS onset was 5 months (range, 0-69 months). Elder age, skin invasion, and necrosis/infection were identified as statistically significant risk factors after CBS by univariate analysis. The presence of skin invasion at the time of treatment found only in postoperative case, is identified as only statistically significant prognostic factor after CBS in multivariate analysis. The 1-year survival rate for the group without skin invasion was 42%, whereas no patient with skin invasion survived more than 4 months (0% at 1 year, p=0.0049). CONCLUSIONS Careful attention should be paid to the occurrence of CBS if the tumor is located adjacent to the carotid artery. The presence of skin invasion at CBS onset is ominous sign of lethal consequences.

Reirradiation of head and neck cancer focusing on hypofractionated stereotactic body radiation therapy

Reirradiation is a feasible option for patients who do not otherwise have treatment options available. Depending on the location and extent of the tumor, reirradiation may be accomplished with external beam radiotherapy, brachytherapy, radiosurgery, or intensity modulated radiation therapy (IMRT). Although there has been limited experience with hypofractionated stereotactic radiotherapy (hSRT), it may have the potential for curative or palliative treatment due to its advanced precision technology, particularly for limited small lesion. On the other hand, severe late adverse reactions are anticipated with reirradiation than with initial radiation therapy. The risk of severe late complications has been reported to be 20- 40% and is related to prior radiotherapy dose, primary site, retreatment radiotherapy dose, treatment volume, and technique. Early researchers have observed lethal bleeding in such patients up to a rate of 14%. Recently, similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT like in case of carotid blowout syndrome. To determine the feasibility and efficacy of reirradiation using modern technology, we reviewed the pertinent literature. The potentially lethal side effects should be kept in mind when reirradiation by hSRT is considered for treatment, and efforts should be made to minimize the risk in any future investigations.

Percutaneous Radiofrequency Ablation Combined with Previous Bronchial Arterial Chemoembolization and Followed by Radiation Therapy for Pulmonary Metastasis from Hepatocellular Carcinoma

A 56-year-old man had a lung metastasis from hepatocellular carcinoma 4.7 cm x 3.4 cm in size located directly adjacent to the pulmonary hilar vessels. The tumor was treated with radiofrequency ablation combined with earlier bronchial arterial chemoembolization and subsequent radiation therapy. A complete remission of the tumor has been observed for 6 months since completion of therapy. Considering that complete treatment of such an intermediate-sized tumor adjacent to the large vessels is usually difficult with radiofrequency ablation alone, this result suggests a possible role for combined therapy for pulmonary neoplasms.

Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: A multi-institutional matched-cohort analysis

BACKGROUND AND PURPOSE Although reirradiation has attracted attention as a potential therapy for recurrent head and neck tumors with the advent of modern radiotherapy, severe rate toxicity such as carotid blowout syndrome (CBOS) limits its potential. The aim of this study was to identify the risk factors of CBOS after hypofractionated stereotactic radiotherapy (SBRT). METHODS AND PATIENTS We conducted a matched-pair design examination of pharyngeal cancer patients treated by CyberKnife reirradiation in four institutes. Twelve cases with CBOS were observed per 60 cases without CBOS cases. Prognostic factors for CBOS were analyzed and a risk classification model was constructed. RESULTS The median prescribed radiation dose was 30 Gy in 5 fractions with CyberKnife SBRT after 60 Gy/30 fractions of previous radiotherapy. The median duration between reirradiation and CBOS onset was 5 months (range, 0-69 months). CBOS cases showed a median survival time of 5.5 months compared to 22.8 months for non-CBOS cases (1-year survival rate, 36% vs.72%; p=0.003). Univariate analysis identified an angle of carotid invasion of >180°, the presence of ulceration, planning treatment volume, and irradiation to lymph node areas as statistically significant predisposing factors for CBOS. Only patients with carotid invasion of >180° developed CBOS (12/50, 24%), whereas no patient with tumor involvement less than a half semicircle around the carotid artery developed CBOS (0/22, 0%, p=0.03). Multivariate Cox hazard model analysis revealed that the presence of ulceration and irradiation to lymph nodes were statistically significant predisposing factors. Thus, we constructed a CBOS risk classification system: CBOS index=(summation of risk factors; carotid invasion >180°, presence of ulceration, lymph node area irradiation). This system sufficiently separated the risk groups. CONCLUSION The presence of ulceration and lymph node irradiation are risk factors of CBOS. The CBOS index, including carotid invasion of >180°, is useful in classifying the risk factors and determining the indications for reirradiation.

Reirradiation using robotic image-guided stereotactic radiotherapy of recurrent head and neck cancer.

The purpose of this study was to examine the prognosis for patients with head and neck cancer after reirradiation using Cyberknife stereotactic body irradiation with special focus on mucosal ulceration. We conducted a retrospective multi-institutional review of 107 patients with previously irradiated head and neck cancer. The median follow-up time for all patients was 15 months, and the 2-year overall survival rate was 35%. Significant prognostic factors for overall survival were primary site (nasopharynx versus other sites), presence of ulceration, and PTV volume. Detailed analysis of ulceration showed a lower response rate (28%) in the ulceration (+) group than the ulceration (−) group (63%; P = 0.0045). The 2-year overall survival rates were 8% in the ulceration (+) group and 42.7% (P = 0.0001) in the ulceration (−) group, respectively. We recorded 22 severe toxicities, including 11 patients with carotid blow-out syndrome (CBOS), which was fatal in 9 patients. CBOS occurred in 6 patients with ulceration (6/25; 24%), and 5 patients experienced CBOS without ulceration (5/82; 6%; P=0.027). In conclusion, ulceration is an important prognostic factor, not only for adverse events but also for survival after reirradiation using CyberKnife.

A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer

S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

Effect of intratumoral abscess/necrosis on the outcome for head and neck cancer patients treated by hypofractionated stereotactic re‑irradiation using CyberKnife®

The aim of the present study was to elucidate the effect of intratumoral abscess/necrosis (AN) on the outcome of patients with recurrent head and neck cancer (HNC) treated by stereotactic radiotherapy. The records of 67 patients treated with CyberKnife® in four institutes between August 2000 and July 2010 were reviewed. The frequency of AN appeared to be increased in younger postoperative patients with large ulcerative tumors. The AN+ group exhibited a better initial response rate compared with the AN− group (64 vs. 33%, respectively; P=0.04). The 1-year local control rate was 51 and 75% in the AN+ and AN− groups, respectively (P=0.01), while the respective 1-year overall survival rates were 53 and and 71% (P=0.0004). A total of 21 patients (31%) experienced grade ≥3 toxicities, and carotid blowout syndrome (CBOS) was found in 11 patients, resulting in 8 deaths. A significantly larger proportion of patients in the AN+ group developed CBOS (8/18; 44%) compared with the AN− group (3/49; 6%) (P=0.001). Therefore, AN may be an important prognostic factor for patients with recurrent HNC, as well as a predictor of lethal toxicity due to CBOS.

The role of dentistry other than oral care in patients undergoing radiotherapy for head and neck cancer

Summary The usefulness of dental approaches, such as oral management, has gained recognition among patients treated for head and neck cancer. In particular, oral management plays a very important role before, during, and after treatment in patients undergoing radiotherapy, chemotherapy, or a combination of both. However, specialized dentistry knowledge and techniques that are useful for patients undergoing radiotherapy for head and neck cancer have yet to be reported. Therefore, in this review article, our aim is to introduce dental approaches in radiotherapy for patients with head and neck cancer that have been developed and are currently being used at our institute.

EP-1634: Comparison of field-in-field radiotherapy with conventional radiotherapy for unilateral cervical lymphoma

Materials and Methods: We analyze 51 patients (48, male; 3 female), aged from 42 to 84 years; diagnosed of lung tumors, and treated with external beam radiotherapy. Radiotherapy treatment was delivered with linear accelerator CLINAC 2100 (Varian). 3D planning was performed with Pinnacle System software (Phillips). For the analysis we select the Dose-Volume Histogram (DVH) parameters mean dose (Dmean) and maximum dose (Dmax). Acute esophageal toxicity was evaluated at end of treatment with the RTOG acute side effects scale Results: Median total dose was 60Gy (45-63 Gy). Mediastinal median dose was 50Gy (45-60Gy) Twenty three patients (45%) did not have esophageal toxicity at end of radiotherapy. Grade 1 was achieved in 23 patients (45%), and grade 2 in 5 (10%) (Fig. 1) Esophageal Dmean: Dmean range: 23.6-33.2Gy. The median of Dmean in patients without toxicity was 31.6 Gy; in patients with toxicity (grade 1 or 2): 33.2 Gy. This difference was not statistically significant (p=0.77) (Fig. 2) Esophageal Dmax: Dmax range: 51-63Gy. The median in patients without toxicity was 58Gy; and median in patients with toxicity (grade 2 or 3): 59.2Gy. These differences were not statistically significant: p=0.289