Tosol Yu

Dose-volumetric Parameters for Predicting Hypothyroidism after Radiotherapy for Head and Neck Cancer

OBJECTIVE To investigate predictors affecting the development of hypothyroidism after radiotherapy for head and neck cancer, focusing on radiation dose-volumetric parameters, and to determine the appropriate radiation dose-volumetric threshold of radiation-induced hypothyroidism. METHODS A total of 114 patients with head and neck cancer whose radiotherapy fields included the thyroid gland were analysed. The purpose of the radiotherapy was either definitive (n = 81) or post-operative (n = 33). Thyroid function was monitored before starting radiotherapy and after completion of radiotherapy at 1 month, 6 months, 1 year and 2 years. A diagnosis of hypothyroidism was based on a thyroid stimulating hormone value greater than the maximum value of laboratory range, regardless of symptoms. In all patients, dose volumetric parameters were analysed. RESULTS Median follow-up duration was 25 months (range; 6-38). Forty-six percent of the patients were diagnosed as hypothyroidism after a median time of 8 months (range; 1-24). There were no significant differences in the distribution of age, gender, surgery, radiotherapy technique and chemotherapy between the euthyroid group and the hypothyroid group. In univariate analysis, the mean dose and V35-V50 results were significantly associated with hypothyroidism. The V45 is the only variable that independently contributes to the prediction of hypothyroidism in multivariate analysis and V45 of 50% was a threshold value. If V45 was <50%, the cumulative incidence of hypothyroidism at 1 year was 22.8%, whereas the incidence was 56.1% if V45 was ≥50% (P = 0.034). CONCLUSIONS The V45 may predict risk of developing hypothyroidism after radiotherapy for head and neck cancer, and a V45 of 50% can be a useful dose-volumetric threshold of radiation-induced hypothyroidism.

Outcome analysis in patients with uterine sarcoma.

Purpose To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. Materials and Methods We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). Results The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. Conclusion The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells

Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer. To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification. Lapatinib down-regulated phosphorylated (p)-HER2, p-epidermal growth factor receptor, p-AKT, and p-extracellular signal-regulated kinase. Pretreatment of lapatinib increased the radiosensitivity of SKBR3 (sensitizer enhancement ratio [SER]: 1.21 at a surviving fraction of 0.5) and BT474 (SER: 1.26 at a surviving fraction of 0.5) cells and hindered the repair of DNA damage, as suggested by the prolongation of radiation-induced γH2AX foci and the down-regulation of phosphorylated DNA-dependent protein kinase, catalytic subunit (p-DNAPKcs). Increases in radiation-induced apoptosis and senescence were suggested to be the major modes of cell death induced by the combination of lapatinib and radiation. Furthermore, lapatinib did not radiosensitize a HER2- negative breast cancer cell line or normal human astrocytes. These findings suggest that lapatinib can potentiate radiation-induced cell death in HER2-overexpressing breast cancer cells and may increase the efficacy of radiotherapy. A phase II clinical trial using lapatinib concurrently with whole-brain radiation therapy (WBRT) is currently being conducted.

Objective Measurement of Cosmetic Outcomes of Breast Conserving Therapy Using BCCT.core

Purpose The purpose of this study is to evaluate objective cosmetic outcomes and factors related to breast-conserving therapy (BCT) using the BCCT.core software. Materials and Methods Fifty-one patients who received BCT with informed consent were evaluated using the BCCT.core software. Patients were divided into two groups based on the BCCT score: excellent or good (n=42) vs. fair or poor (n=9). Analysis of clinical factors was performed to determine factors affecting cosmetic outcomes. Results The objective cosmetic outcome of BCT measured using the BCCT.core software was excellent in 10% of patients, good in 72%, and fair in 18%. None of the patients were classified as poor outcome. Tumor characteristics, systemic adjuvant therapy (chemotherapy and hormonal therapy), and radiation dose or energy of electron boost did not show correlation with the score measured by the BCCT.core program (p > 0.05). In univariate analysis, maximum dose within the breast (Dmax), width of tangential field, and excised tumor volume were smaller in patients with excellent or good by the BCCT.core compared to those with fair or poor (Dmax, 110.2±1.5% vs. 111.6±1.7%, p=0.019; width of tangential field, 8.0±1.1 cm vs. 8.6±0.7 cm, p=0.034; excised tumor volume, 64.0±35.8 cm3 vs. 95.3±54.4 cm3, p=0.067). In multivariate analysis, only Dmax was a significant factor for breast cosmetic outcome with a risk ratio of 1.697 (95% confidence interval, 1.006 to 2.863; p=0.047). Conclusion Objective measurement of cosmetic outcome of BCT using the BCCT.core software was feasible. The cosmetic outcome of BCT may be affected by the maximum dose within the breast.

Fluorodeoxyglucose positron-emission tomography ratio in non-small cell lung cancer patients treated with definitive radiotherapy

Purpose To determine whether the maximum standardized uptake value (SUV) of [18F] fluorodeoxyglucose uptake by positron emission tomography (FDG PET) ratio of lymph node to primary tumor (mSUVR) could be a prognostic factor for node positive non-small cell lung cancer (NSCLC) patients treated with definitive radiotherapy (RT). Materials and Methods A total of 68 NSCLC T1-4, N1-3, M0 patients underwent FDG PET before RT. Optimal cutoff values of mSUVR were chosen based on overall survival (OS). Independent prognosticators were identified by Cox regression analysis. Results The most significant cutoff value for mSUVR was 0.9 with respect to OS. Two-year OS was 17% for patients with mSUVR > 0.9 and 49% for those with mSUVR ≤ 0.9 (p = 0.01). In a multivariate analysis, including age, performance status, stage, use of chemotherapy, and mSUVR, only performance status (p = 0.05) and mSUVR > 0.9 (p = 0.05) were significant predictors of OS. Two-year OS for patients with both good performance (Eastern Cooperative Oncology Group [ECOG] ≤ 1) and mSUVR ≤ 0.9 was significantly better than that for patients with either poor performance (ECOG > 1) or mSUVR > 0.9, 23% (71% vs. 23%, p = 0.04). Conclusion Our results suggested that the mSUVR was a strong prognostic factor among patients with lymph node positive NSCLC following RT. Addition of mSUVR to performance status identifies a subgroup at highest risk for death after RT.

Study design and early result of a phase I study of SABR for early-stage glottic cancer: SABR for Early Glottic Cancer

Avoidance of organs at risk has become possible with advances in image‐guided volumetric‐modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level.

Does fluid collection impact radiotherapy outcomes after wide excision of lower extremity soft tissue sarcoma

Background Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS). Methods Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively. Results After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC. Conclusions FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.