Yu-Fu Su

Intensity modulated radiotherapy with concurrent chemotherapy for larynx preservation of advanced resectable hypopharyngeal cancer

BackgroundTo analyze the rate of larynx preservation in patients of locally advanced hypopharyngeal cancer treated with intensity modulated radiotherapy (IMRT) plus concurrent chemotherapy, and compare the results with patients treated with primary surgery.MethodsBetween January 2003 and November 2007, 14 patients were treated with primary surgery and 33 patients were treated with concurrent chemoradiotherapy (CCRT) using IMRT technique. Survival rate, larynx preservation rate were calculated with the Kaplan-Meier method. Multivariate analysis was conducted for significant prognostic factors with Cox-regression method.ResultsThe median follow-up was 19.4 months for all patients, and 25.8 months for those alive. The 5-year overall survival rate was 33% and 44% for primary surgery and definitive CCRT, respectively (p = 0.788). The 5-year functional larynx-preservation survival after IMRT was 40%. Acute toxicities were common, but usually tolerable. The rates of treatment-related mucositis (≥ grade 2) and pharyngitis (≥ grade 3) were higher in the CCRT group. For multivariate analysis, treatment response and cricoid cartilage invasion strongly correlated with survival.ConclusionsIMRT plus concurrent chemotherapy may preserve the larynx without compromising survival. Further studies on new effective therapeutic agents are essential.

Dosimetric and efficiency comparison of high‐dose radiotherapy for esophageal cancer: volumetric modulated arc therapy versus fixed‐field intensity‐modulated radiotherapy

The aim of this study was to compare high-dose volumetric modulated arc therapy (VMAT) and fixed-field intensity-modulated radiotherapy (ff-IMRT) plans for the treatment of patients with middle-thoracic esophageal cancer. Eight patients with cT2-3N0M0 middle-thoracic esophageal cancer were enrolled. The treatment planning system was the version 9 of the Pinnacle(3) with SmartArc (Philips Healthcare, Fitchburg, WI, USA). VMAT and ff-IMRT treatment plans were generated for each case, and both techniques were used to deliver 50 Gy to the planning target volume (PTV(50)) and then provided a 16-Gy boost (PTV(66)). The VMAT plans provided superior PTV(66) coverage compared with the ff-IMRT plans (P = 0.034), whereas the ff-IMRT plans provided more appropriate dose homogeneity to the PTV(50) (P = 0.017). In the lung, the V(5) and V(10) were lower for the ff-IMRT plans than for the VMAT plans, whereas the V(20) was lower for the VMAT plans. The delivery time was significantly shorter for the VMAT plans than for the ff-IMRT plans (P = 0.012). In addition, the VMAT plans delivered fewer monitor units. The VMAT technique required a shorter planning time than the ff-IMRT technique (3.8 ± 0.8 hours vs. 5.4 ± 0.6 hours, P = 0.011). The major advantages of VMAT plans are higher efficiency and an approximately 50% reduction in delivery time compared with the ff-IMRT plans, with comparable plan quality. Further clinical investigations to evaluate the use of high-dose VMAT for the treatment of esophageal cancer are warranted.

Risk of hypothyroidism among patients with nasopharyngeal carcinoma treated with radiation therapy: A Population-Based Cohort Study

BACKGROUND AND PURPOSE This study aimed to assess the incidence and risk of hypothyroidism among patients with nasopharyngeal carcinoma (NPC) after radiation therapy (RT). MATERIAL AND METHODS We identified 14,893 NPC patients and 16,105 other head and neck cancer (HNC) patients treated with RT without thyroidectomy from the National Health Insurance Research Database in Taiwan between 2000 and 2011. Each NPC patient was randomly frequency-matched with four individuals without NPC by age, sex, and index year. Competing-risk regression models were used to estimate hazard ratios (HRs) of hypothyroidism requiring thyroxin associated with NPC after RT. RESULTS The risk of developing hypothyroidism was significantly higher in the NPC cohort than in the matched cohort (adjusted HR=14.35, 95% CI=11.85-17.37) and the HNC cohort (adjusted HR=2.06, 95% CI=1.69-2.52). Independent risk factors for hypothyroidism among NPC patients included younger age, female sex, higher urbanization level, autoimmune disease, and receipt of chemotherapy. CONCLUSION The risk of hypothyroidism requiring thyroxin was significantly higher in NPC patients after RT than in the general Taiwanese population and HNC patients. Regular clinical and serum thyroid function tests are essential among NPC survivors after RT.

Stereotactic ablative radiotherapy for patients with unresectable or medically inoperable cholangiocarcinoma

Purpose The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. Methods From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. Results The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Conclusions Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

The Outcome of CyberKnife Treatment for Primary or Metastatic Malignant Lung Tumors

Background: To analyze the local control of malignant lung tumors and survival of nonsmall cell lung cancer (NSCLC) patients after stereotactic ablative radiotherapy with CyberKnife. Materials and Methods: Patients with malignant lung tumors treated by CyberKnife between July 2007 and October 2010 at our institute were retrospectively reviewed. A total of 55 patients with 110 malignant lung tumors were included. There were 32 men and 23 women, and the median age was 67 years. There were 11 early-stage NSCLCs, while the other 44 patients with 99 lesions were metastatic lung tumors. The median gross tumor volume was 13.3 ml. Radiotherapy schedules include 40-60 Gy in 4-5 fractions, 45-60 Gy in 3 fractions and 30 Gy in 1 fraction. Results: The median follow-up time for patients alive was 34 months. The local control rates for all tumors were 96% at 1-year and 80% at 2 years. Univariate analysis demonstrated that target volume was important for local control. Biologically equivalent dose (BED) ≥100 Gy provided significantly higher chance to achieve a complete response than BED ＜100 Gy. The disease-specific survival rates for early-stage NSCLC were 80% at 1-year and 60% at 2 years. Treatment related complications were acceptable. No grade 2-5 adverse events were noted. Conclusions: CyberKnife can be used for NSCLC and metastatic lung tumors, either peripheral or central location, with good local control and acceptable side-effects.

Advanced Thymic Carcinoma: Clinical Experience and Prognostic Factors of 18 Patients

Purpose: Thymic carcinoma is an uncommon but lethal malignancy. We analyze the outcomes and prognostic factors of patients with advanced thymic carcinoma treated at a single institution.Materials and Methods: The records of 18 patients with histologically confirmed thymic carcinoma treated between April 1996 and April 2012 at Tri-Service General Hospital were retrospectively reviewed. Surgical resection was performed in 9 patients, including 3 patients who received preoperative therapy and postoperative chemoradiotherapy followed by chemotherapy, 5 who received postoperative chemoradiotherapy followed by chemotherapy and 1 who received postoperative radiotherapy alone. Eight patients had tumor which were unresectable or medically inoperable and underwent chemoradiotherapy followed by chemotherapy or radiotherapy alone. One patient died 2 months after diagnosis without any cancer treatment. Radiotherapy was delivered with three-dimensional conformal radiation therapy, intensity-modulated radiation therapy or stereotactic ablative radiotherapy using Cyberknife (Accuray, Inc., Sunnyvale, CA). The median dose of radiotherapy was 63 Gy. Most (93.3%) of the chemotherapy regimen contained cisplatin.Results: The distribution of Masaoka stage at presentation was III in 7 patients, IVA in 4 patients and IVB in 7 patients. The 5-year overall survival (OS) rate and 3-year progression-free survival (PFS) rate were 46.5% and 32.1%, respectively. The 5-year in-field tumor control rate of 17 patients who underwent radiotherapy was80.9%. Univariate statistical analysis revealed that radiotherapy ≧ 65 Gy was the only statistically significant predictor of outcome. A total radiation dose of ≧ 65 Gy results in improved 3-year OS (100% vs. 13.1%, p= 0.004) and 3-year PFS (47.6% vs. 16%, p=0.044) in patients with thymic carcinoma. The survival benefit of receiving radiotherapy ≧ 65 Gy was apparent in the unresected group of patients with thymic carcinoma.Conclusions: Aggressive multidisciplinary treatments including surgery, radiotherapy, and chemotherapy, are helpful in treating advanced thymic carcinoma. Radiotherapy with dose above 65 Gy may improve the OS and PFS of patients with advanced thymic carcinoma, especially in the unresected group.

Comparing Stereotactic Body Radiotherapy with Three-Dimensional Conformal Radiotherapy for Patients with Unresectable or Recurrent Hepatocellular Carcinoma

Purpose: To compare stereotactic body radiotherapy (SBRT) with three-dimensional conformal radiotherapy (3D-CRT) for improving hepatocellullar carcimona (HCC) patient survival rates.Material and Method: Forty-one patients with unresectable or recurrent HCC were divided into one group of 20 patients who received SBRT, and another group of 21 patients who received 3D-CRT. They were treated in the Radiation Oncology Department of the Tri-Service General Hospital from March 2007 to March 2009. The median follow-up time for all patients was 12 months (range 2 to 36 months). Overall survival was the primary end point.Results: For the 3D-CRT and SBRT patient groups, the median survival (MS) was 11 months and 16 months with the 1-year overall survival (OS) of 42.9% and 70.0%, respectively. In the univariate analysis, CyberKnife SBRT (p= 0.019), non-advanced Okuda stage (p= 0.002), serum albumin higher than 3.5g /dl (p= 0.008), and total bilirubin lower than 2.0 mg/dL (p= 0.042) were associated with significantly better OS. Further statistical analyses showed that those patients in Child-Pugh class A who received SBRT had better OS than those who received 3D-CRT (p= 0.047). Multivariate analyses revealed that Okuda stage (p= 0.006). Child-Pugh class (p= 0.042) and technique of RT (p= 0.029) were significant prognostic factors for OS.Conclusions: This study showed that patients who received SBRT had significantly better OS than those who received 3D-CRT. SBRT has the advantage of short overall treatment times compared to 3D-CRT. Our results also suggest that SBRT could be considered first in patients with Child-Pugh class A. Further study is required to define the effects of administered radiation dose and fractionation.

Comparison of Treatment Results of Malignant Astrocytoma after post-op Radiotherapy Alone or post-op Concurrent Chemoradiotherapy plus Adjuvant chemotherapy-Experience in TSGH

Purpose: To analyze the treatment results of malignant astrocytoma after radiotherapy alone or concurrent chemoradiotherapy plus adjuvant chemotherapy in TSGH. Methods and Materials: From April 2002 to December 2007, we identified 35 patients with documented, histologically confirmed, previously untreated glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). They were treated with surgical resection followed by radiotherapy alone or chemoradiotherapy in our hospital. A total of 60 Gy was given in 6 weeks with 3D conformal RT (3D-CRT). Fusion of planning CT with MRI was routinely used to assist target delineation. We used concomitant temozolomide (75 mg/m^2 daily up to 49 days) followed by up to six cycles of adjuvant temozolomide (150 to 200 mg/m^2 daily for five days, every 28 days). Follow-up and survival times were calculated from the date of diagnosis to the date of last contact or death. Disease-free survival (DFS) and overall survival (OS) were computed by Kaplan-Meier methods. Results: The median follow-up was 19.1 months. At the time of analysis, 10 patients were alive, 25 patients had died. The median survival rate was 19.1 months for all patients. The 3-year overall survival rates were 14% and 43% in radiotherapy alone arm and CCRT arm, respectively. (p=0.002). The 3-year progression-free survival rates were 10.6% and 13.9% in radiotherapy alone and CCRT arm, respectively. (p=0.54). In the AA group, the overall survival rates were 8.7% and 67.9% in radiotherapy alone arm and CCRT arm, respectively. (p=0.001). In the GBM group, the overall survival rates were 16.3% and 23.7% in radiotherapy alone and CCRT arm, respectively. (p=0.261). In-field failure was the major cause of failure, among 35 patients, 22 (62.8%) patients had in-field failure. All patients completed radiotherapy courses. Thirty (86%) patients had grade 1 CNS toxicity and 5 (14%) patients had grade 2 CNS toxicity. Among 21 patients who received temozolomide, 18 patients had no obvious side effects during and after chemotherapy. Conclusions: Addition of adjuvant chemotherapy with temozolomide to radiotherapy for patients with newly diagnosed AA and GBM has statistically significant survival benefit especially for patients of AA with tolerable toxicity.

Second Primary Malignancies in Patients with Nasopharyngeal Cancer after Radiotherapy: A 38-Year Follow-Up

Purpose: To define the incidence and risk of the second primary malignancies (SPM) in patients with nasopharyngeal cancer (NPC) post radiotherapy in our hospital. We also analyze their prognosis after the SPM Materials and Method: Between April 1971 and April 2009, 1367 patients were indentified to have NPC after definitive radiotherapy. Of them, 45 patients developed SPM. They received various treatment strategies including surgery with or without adjuvant radiotherapy, concurrent chemoradiotherapy or radiotherapy alone. Radiotherapy technique included conventional radiotherapy, three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). Results: The most common site for a SPM was the head and neck region, lung, liver and leukemia & lymphoma in decreasing order. The median time to development of SPM was 94 months. The crude incidence was 3.3%. The 20-year cumulative rate of development of SPM was 16.7%. Older patient has a higher incidence of 39.1%. The incidence between patients who received conventional radiotherapy and those having 3DCRT or IMRT is not significantly different (p=0.666). There is no significant difference for survival in NPC with or without SPM (p=0.245). Conclusions: Head and neck cancer is the most common second cancer in NPC patients after radiotherapy. There is a trend to the development of SPM in the older age groups (＞50 years old)

Treatment Results of Esophageal Cancer after Radiotherapy Alone or Concurrent Chemoradiothepapy

Purpose: To analyze the treatment results of the patients with esophageal cancer after radiotherapy (RT) alone or concurrent chemoradiotherapy (CCRT) and identify possible prognostic factors. Methods and Materials: Between February 1997 and February 2007, we treated 118 patients who had previously untreated esophageal carcinoma using definitive RT alone or CCRT. Fifty-two patients (44.1%) underwent RT alone and 66 patients (55.9%) underwent CCRT. Radiotherapy was delivered with conventional technique in 58 patients, three-dimensional conformal radiation therapy (3DCRT) in 56 patients, and intensity-modulated radiation therapy (IMAT) in 4 patients. The median dose of RT was 59.4 Gy. Survival rates were calculated from the end of the radiotherapy with the Kaplan-Meier method. Results: The median follow-up was 4 months for all patients and 25 months for those alive. Ten patients were alive, 102 patients died, and 6 patients were lost to follow-up. The 4-year overall survival of all patients were 8.2%. The 4-year overall survival of the patients in the RT alone and the CORT arm was 2.7% and 13.8%, respectively (p=0.188). The 4-year overall survival rate of stage Ⅱ, Ⅲ, and Ⅳ Was 9%, 14.6%, and 0%, respectively (p=0.045). There is no survival benefit for patient treated with 3DCRT or IMRT compared with conventional technique. A higher pretreatment hemoglobin (10 gm/dl or more) resulted in a better survival (p=0.001). In multivariate analysis, stage, CCRT, pretreatment hemoglobin, and completion of RT course were significant predictors of survival (p=0.033, 0.046, 0.032, ＜0.001, respectively). Adding chemotherapy to radiotherapy did not increase treatment mortality and morbidity. Three-dimensional conformal radiation therapy (3DCRT)/IMRT decreased incidence of radiation pneumonitis compared with conventional technique (p=0.011). Conclusions: There is a trend for a better survival in the CCRT group and adding chemotherapy did not bring more toxicities. Higher pretreatment hemoglobin, early stage, CCRT, completion of AT course were significant predictors of better survival. New AT technique with 3DCRT/IMRT did not offer survival benefit, but decreased incidence of radiation pneumonitis.