Naohiro Kodani

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

BackgroundTo assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.MethodsWe quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.ResultsThe median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm3 (range, 7.17 - 14.3 cm3) and 1.99 for pituitary adenoma, and 6.86 cm3 (range 6.05 - 14.6 cm3) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm3 for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm3(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm3) than group 2 (6.91 ± 0.7 cm3, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.ConclusionQuality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.

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.

Outcome and toxicity of stereotactic body radiotherapy with helical tomotherapy for inoperable lung tumor: analysis of Grade 5 radiation pneumonitis

To analyze outcomes and toxicities of stereotactic body radiotherapy with helical tomotherapy (HT-SBRT) for inoperable lung tumors, the medical records of 30 patients with 31 lung tumors treated with HT-SBRT were reviewed. The 3-year local control, cause-specific survival and overall survival rates (LC, CCS and OS, respectively) were analyzed using the Kaplan–Meier method. Toxicities were graded using Common Terminology Criteria for Adverse Events ver. 4. To investigate the factors associated with Grade 5 radiation pneumonitis (G5 RP), several parameters were analyzed: (i) patient-specific factors (age, gross tumor volume and PTV, and the interstitial pulmonary shadow on pretreatment CT); and (ii) dosimetry-specific factors (conformity index, homogeneity index, mean lung dose, and V5, V10, V15, V20 and V25 of the total lungs). The median duration of observation for all patients was 36.5 months (range, 4–67 months). The 3-year LC, CCS and OS were 82, 84 and 77%, respectively. Regarding Grade 3 or higher toxicities, two patients (6.7%) developed G5 RP. GTV was significantly associated with G5 RP (P = 0.025), and there were non-significant but slight associations with developing G5 RP for V5 (P = 0.067) and PTV (P = 0.096). HT-SBRT led to standard values of LC, CCS and OS, but also caused a markedly higher incidence of G5 RP. It is essential to optimize patient selection so as to avoid severe radiation pneumonitis in HT-SBRT.

Association between Skin Phototype and Radiation Dermatitis in Patients with Breast Cancer Treated with Breast-conserving Therapy: Suntan Reaction could be a Good Predictor for Radiation Pigmentation

Breast-conserving therapy/Breast cancer/Radiation dermatitis. The purpose of this study was to evaluate the significance of skin phototype (suntan or sunburn type) i n association with radiation dermatitis in patients with breast cancer who underwent postoperative radiotherapy after breast-conserving surgery because phototype could predict sunlight reaction. We divided patie nts into two phototypes (58 suntan/darkening and 28 sunburn/reddening types) according to selfreports before radiotherapy. We examined skin color changes in 86 patients who underwent breastconserving surgery followed by 50 Gy/25 fractions (median) of radiotherapy with or without boost radiation (10 Gy/5 fractions). Color change was assessed according to CIE L*a*b* space, which is defined by th e Commission Internationale de l’Eclairage (CIE) in 1976 for quantitative color assessment. The patients were also assessed by individual typology angle (ITA°; indicator of skin color calculated by L*a*b* space) and Common Terminology Criteria for Adverse Event v3.0 (CTCAE v3). Radiation therapy changed all values except the b* value, and the suntan type showed a greater darkening response associated with radiation dermatitis than did the sunburn type in terms of ITA° value change (p = 0.04), whereas the sunburn type did not show higher a* value (reddening). By CTCAE v3 classifications, a Grade 2 reaction appeared in 14% sunburn patients and in 31% of the suntan group, respectively (p = 0.16 ). Suntan type predicted higher pigmentation associated with radiation dermatitis. Self-reported phototype has the potential to be a good predictor of skin sensitivity to radiation exposure for clinical screening.

Evaluation of dosimetry and excess seeds in permanent brachytherapy using a modified hybrid method: a single-institution experience

Permanent prostate brachytherapy is frequently performed worldwide, and many studies have demonstrated its favorable outcomes. Implant seeds used in this procedure contain a precise amount of radionuclide and are completely sealed. Because these seeds are not manufactured in Japan, they are expensive (6300 yen per seed) and therefore need careful management as a radioisotope. The proper implantation technique requires considerable procedure time, good dosimetric outcomes and simple radioactive isotope management. To evaluate the modified hybrid interactive technique based on these considerations, we assessed 313 patients who underwent hybrid interactive brachytherapy without additional external beam radiotherapy. We evaluated the duration of the procedure, dosimetric factors and the total number of excess seeds. The dosimetric results from computed tomography on Day 30 of follow-up were: 172 Gy (range 130–194 Gy) for pD90, 97.8% (83.5–100%) for pV100, 54.6% (27.5–82.4%) for pV150, 164 Gy (120–220 Gy) for uD90, 194 Gy (126–245 Gy) for uD30, 210 Gy (156–290 Gy) for uD5, 0.02 ml (0–1.2 ml) for rV100 and 0 ml (0–0.2 ml) for rV150. The number of excess seeds was determined by subtracting the number of implanted seeds from the expected number of seeds calculated from previously proposed nomograms. As per our method, nine excess seeds were used for two patients, whereas using the nomograms, the number of excess seeds was approximately eight per patient. Our modified hybrid interactive technique reduced the number of excess seeds while maintaining treatment quality.

Utility of additional delayed post-therapeutic ¹³¹I whole-body scanning in patients with thyroid cancer.

Objective: The purpose of this study is to compare early (3 days after administration) and delayed (7–9 days after administration) post-therapeutic 131I scanning for detecting metastatic lesions from differentiated thyroid carcinoma. Methods: This study included 24 patients (10 men and 14 women) with differentiated thyroid carcinoma who underwent early and delayed whole-body scanning after 131I treatment. The early and delayed scan images were visually analyzed, and the region-to-whole-body ratio (RBR) and its variation from the early to delayed scanning (RBR variation) were calculated. Results: In the visual analysis, lung metastases in 2 patients and 1 bone metastasis could not be detected on early scanning but were classified as moderate uptake on delayed scanning. The abdomen showed definite uptake on early scanning but was washed out on delayed scanning. The RBR variation of the lung and bone metastases was significantly higher than those of the abdomen and thyroid remnants. This suggests that the distribution of 131I was more quickly washed out of the abdomen and thyroid remnants than from the metastatic lesions. Conclusions: Delayed scanning showed a higher detection rate of lung and bone metastases than early scanning because of the washout of the physiological distributions. Additional delayed scanning is recommended, especially for high-risk patients with intensive physiological distribution on early scanning.

A Case of Thyroid Papillary Carcinoma: Remarkable Decrease in Multiple Lung Metastases within 40 Years after a Single Administration of Radioiodine without Thyroidectomy and with Later Anaplastic Transformation

Differentiated thyroid carcinoma is an uncommon malignancy of childhood and adolescence that is unique because it has an overall favorable prognosis despite its relatively high rate of nodal and distant metastases. Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies that have an unfavorable and miserable prognosis. We report a case with an impressively long history. The patient had multiple pulmonary metastases that had been diagnosed by 131I administration when he was 14 years old, about 45 years before he underwent thyroidectomy. He had been kept unaware of his disease by his family and received no treatment for most of his life. Pulmonary nodules were noted at several medical checkups and showed a remarkable decrease in size during the untreated 44-year period after the 131I administration. At age 58, his thyroid cancer was first detected and total thyroidectomy was performed, with subsequent radioiodine therapy for pulmonary metastases. Unfortunately, anaplastic carcinoma developed and he died of disseminated tumors later.