Hsing-Lung Chao

Squamous cell carcinoma of the buccal mucosa: An aggressive cancer requiring multimodality treatment

In our clinical practice, we have observed a high incidence of locoregional failure in squamous cell carcinoma (SCC) of the buccal mucosa. We analyze our treatment results of this cancer and compare these results with those in the literature. We intend to define the pattern and incidence of failure of buccal cancer and provide information for the design of a better multimodality treatment.

DOSE ESCALATION USING TWICE-DAILY RADIOTHERAPY FOR NASOPHARYNGEAL CARCINOMA: DOES HEAVIER DOSING RESULT IN A HAPPIER ENDING?

PURPOSE To present our experience using a twice-daily radiotherapy (RT) technique, including hyperfractionated and accelerated-hyperfractionated RT, on nasopharyngeal carcinoma (NPC) patients. The dose to the primary tumor was increased in the hope that local control could be increased without the cost of increased late complications. We analyzed acute and late complications and local control and compared the results with the results of NPC patients treated during the same period using conventional once-daily RT. METHODS AND MATERIALS Between October 1991 and July 1998, 222 histologically confirmed, Stage M0, previously unirradiated NPC patients completed RT at our hospital. Most patients had American Joint Committee on Cancer (AJCC) 1992 Stage III and IV disease. Among them, 88 received altered fractionated, twice-daily RT; 76 patients received hyperfractionated RT and 12 accelerated-hyperfractionated RT. The remaining 134 patients received a conventional once-daily regimen. Hyperfractionated RT was delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course. For the accelerated-hyperfractionated patients, 160 cGy b.i.d. was given, also at 6-h intervals. The median dose in the twice-daily group was 7810 cGy (range 6840-8200). In the once-daily regimen, RT was delivered using 180-200 cGy q.d. The median tumor dose to the primary tumor was 7000 cGy (range 6560-8100) given during about 8 weeks. The median follow-up time was 70.5 and 72 months for the twice-daily and once-daily groups, respectively. RESULTS The incidence of acute toxicities was higher in the twice-daily group with more severe mucositis and moist desquamation than in the once-daily group. Both groups had a similar incidence of late complications, except for 3 cases of temporal lobe necrosis in the twice-daily group, all in patients treated with 160 cGy. No difference was noted in recurrence-free local control between the two groups when the individual T stage was compared using AJCC 1992 or 1997 criteria (p = 0.51 and 0.59, respectively). The 5-year local control rate for T1-3 (AJCC 1997) was 93.2% for the twice-daily group and 86.4% for the once-daily group (p = 0.45). In Stage T4 (AJCC 1997) patients, the local control rate dropped drastically to 43.5% and 36.9% for the twice-daily and once-daily groups, respectively. The overall neck control rate at 5 years was 87.3% and 80.3% for the twice-daily and once-daily patients, respectively (p = 0.16). The overall locoregional control rate was 82.7% for the twice-daily group and 66.6% for the once-daily group. The difference was again not statistically significant, but showed a tendency in favor of the twice-daily regimen (p = 0.055). Locoregional failure occurred mainly in Stage T4 patients with central nervous invasion for whom local control was particularly poor, with a failure rate of about 60%. CONCLUSION The present data suggest that NPC patients can be safely treated using a 120-cGy twice-daily program with a 6-h interval up to 8000 cGy. The accelerated-hyperfractionated technique is not recommended. A large discrepancy in local control between patients with T1-3 and T4 disease was noted. For T1-3 disease, an excellent local control rate >90% was achieved using the twice-daily regimen. In contrast, failure in the T4 patients was as high as 55% in the twice-daily group and reached 65% in the once-daily group. More rigorous treatment is needed using either additional dose escalation or other strategies for T4 NPC patients. With a dose escalation of 1000 cGy using 120-cGy twice-daily RT, a trend toward better locoregional control and disease-specific survival was noted in the twice-daily group. Whether this difference was truly the result of an increased dose needs additional confirmation in studies with larger patient numbers.

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.

18F-FDG PET and Combined 18F-FDG–Contrast CT Parameters as Predictors of Tumor Control for Hepatocellular Carcinoma After Stereotactic Ablative Radiotherapy

The application of stereotactic ablative radiotherapy (SABR) to hepatocellular carcinoma (HCC) is emerging. To identify pretreatment prognostic indicators is crucial for patient selection and optimal individual therapy. The aim of this study was to determine whether 18F-FDG PET and a combined 18F-FDG–contrast CT parameter could be useful tools to predict tumor control for patients with HCC treated by SABR. Methods: We retrospectively identified 31 patients (41 tumors) who underwent 18F-FDG PET before SABR between November 2007 and September 2011. 18F-FDG PET parameters were collected as prognostic indicators, including visual PET scale (+/−), maximal standardized uptake value (SUV) of the tumor (TSUVmax), ratio of TSUVmax to maximal normal-liver SUV, ratio of TSUVmax to mean normal-liver SUV, and score combining tumor volume and TSUVmax (CT/18F-FDG PET score). They underwent SABR with a median dose of 42 Gy (ranging from 30 to 50 Gy) in 4–5 fractions. 18F-FDG PET parameters and clinical factors were tested as predictors of tumor control and patient survival. Results: The median follow-up time was 18 mo. Among the parameters examined, TSUVmax and CT/18F-FDG PET score were significantly correlated with tumor control. TSUVmax with a cutoff value of 3.2 was the most significant prognostic indicator. The 4-y control rate was 86.2% in tumors with a TSUVmax of 3.2 or less but only 37.5% in those with a TSUVmax of more than 3.2 (adjusted hazard ratio, 9.40; 95% confidence interval, 1.18–74.76; P = 0.034). CT/18F-FDG PET score (≤4 vs. >4) was also a significant predictor of tumor control after SABR. Tumors with a CT/18F-FDG PET score of more than 4 had a 5.23-fold risk of tumor failure. After adjustment for factors of sex, American Joint Committee on Cancer stage, Cancer of the Liver Italian Program score, and Child–Pugh classification, tumors with a score of more than 4 had a 4.96-fold risk of failure after SABR, compared with tumors with a score of 4 or less. For overall survival, none was statistically significant. Conclusion: The use of 18F FDG PET to predict tumor control is feasible. TSUVmax with a cutoff value of 3.2 is the best prognostic indicator. We suggest that 18F-FDG PET may be a reference for prognostic prediction, patient selection, and radiation dose adjustment for HCC patients treated with SABR.

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.

Long-Term Breast Cancer Patient Outcomes After Adjuvant Radiotherapy Using Intensity-Modulated Radiotherapy or Conventional Tangential Radiotherapy

AbstractThe aim of the article is to analyze breast cancer patient clinical outcomes after long-term follow-up using intensity-modulated radiotherapy (IMRT) or conventional tangential radiotherapy (cRT).We retrospectively reviewed patients with stage 0–III breast cancer who received breast conserving therapy between April 2004 and December 2007. Of the 234 patients, 103 (44%) were treated with IMRT and 131 (56%) were treated with cRT. A total prescription dose of 45 to 50 Gy (1.8–2 Gy per fraction) was delivered to the whole breast. A 14 Gy boost dose was delivered in 7 fractions. The median follow-up was 8.2 years.Five of 131 (3.8%) cRT-treated patients and 2 of 103 (1.9%) IMRT-treated patients had loco-regional failure. The 8-year loco-regional failure-free survival rates were 96.7% and 97.6% (P = 0.393) in the cRT and IMRT groups, respectively, whereas the 8-year disease-free survival (DFS) rates were 91.2% and 93.1%, respectively (P = 0.243). Patients treated with IMRT developed ≥ grade 2 acute dermatitis less frequently than patients treated with cRT (40.8% vs 56.5%; P = 0.017). There were no differences in late toxicity.IMRT reduces ≥ grade 2 acute skin toxicity. Local control, DFS, and overall survival were equivalent with IMRT and cRT. IMRT can be considered a standard technique for breast cancer treatment.

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results.

Aims and Background Recent clinical reports of stereotactic ablative radiotherapy (SABR) in the treatment of low-risk prostate cancer have been encouraging. Our study evaluates the efficacy and safety of SABR using the CyberKnife system for treating intermediate- to very-high-risk prostate cancer. Methods and Study Design Between May 2010 and June 2013, 31 patients (15 intermediate risk, 14 high risk, and 2 very high risk) without pelvic lymph node metastasis were enrolled retrospectively. The treatment consisted of 37.5 Gy in 5 fractions over 1-2 weeks using CyberKnife SABR. Twenty-five patients (81%) received androgen deprivation therapy (ADT). Biochemical failure was defined using the nadir + 2 criterion. Toxicity was assessed with the Common Terminology Criteria of Adverse Events (version 4). Results The median follow-up was 36 months (range 7-58 months). The median pretreatment prostate-pecific antigen (PSA) was 13.5 ng/mL (range 4.5-124.0 ng/mL). The median PSA decreased to 0.09 ng/mL (range <0.04-5.38 ng/mL) and 0.12 ng/mL (range <0.04-2.63 ng/mL) at 6 months and 12 months after SABR, respectively. The 3-year biochemical relapse-free survival was 90.2% for all patients, 100% for the intermediate-risk patients, and 82% for the high- and very-high-risk patients (p = 0.186). No patient experienced ≥ grade 3 toxicity. There were 7 acute and 5 late grade 2 genitourinary toxicities and 1 acute and no late grade 2 gastrointestinal toxicity. Conclusions Our preliminary results support that CyberKnife SABR with ADT is safe and feasible in patients with intermediate- to high-risk prostate cancer. A further large-scale clinical trial with longer follow-up is 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.

Risk of depressive disorder among patients with head and neck cancer: A nationwide population‐based study

The purpose of this study was to assess the incidence and risk of depressive disorder among patients with head and neck cancer.

Survival and prognostic factors for patients with advanced hepatocellular carcinoma after stereotactic ablative radiotherapy

Objective To evaluate the survival outcomes and prognostic factors of patients with advanced hepatocellular carcinoma (HCC) who underwent stereotactic ablative radiotherapy (SABR). Methods This retrospective study evaluated patients with advanced HCC who underwent SABR between December 2007 and July 2015. All patients had Barcelona Clinic Liver Cancer stage C disease and Child–Turcotte–Pugh (CTP) class A–B function. In-field control (IFC), overall survival (OS), prognostic factors, and toxicity were evaluated. Results In this study of 89 patients, the 3-year IFC rate was 78.1%, and the 1-year and 3-year OS rates were 45.9% and 24.3%, respectively. The multivariate analysis revealed that CTP class, the presence of main portal vein tumor thrombosis, and the presence of extrahepatic spread were independent predictors of OS. The expected median OS values among patients with ≥2, 1, and 0 predictors were 4.2, 8.6, and 26.4 months, respectively (p <0.001). Conclusions SABR may be useful for patients with advanced HCC, and patient selection could be based on the CTP classification, main portal vein tumor thrombosis, and extrahepatic spread.