Comparison of Stereotactic Body Radiation Therapy and Transarterial Chemoembolization for Unresectable Medium-Sized Hepatocellular Carcinoma.

PURPOSE: This study compared the local control and overall survival (OS) between stereotactic body radiation therapy (SBRT) and transarterial chemoembolization (TACE) in medium-sized (3-8 cm) hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From January 2008 to October 2017, 188 patients with medium-sized HCC underwent either TACE (n = 142) or SBRT (n = 46). We adjusted for imbalances in treatment assignment using propensity score matching. Infield control (IFC) and OS were analyzed retrospectively. RESULTS: The median follow-up time was 17.1 months for all patients and 26.6 months for surviving patients. The 3-year IFC was 63.0% for the TACE group and 73.3% for the SBRT group. Multivariable analysis identified the independent predictors for IFC as treatment modality (SBRT vs TACE), sex (female vs male), and recurrence status (recurrence vs new diagnosis). The 3-year OS was 22.9% for the TACE group and 47.4% for the SBRT group. Multivariable analysis identified the independent predictors of OS as number of tumors, treatment modality (SBRT vs TACE), albumin-bilirubin grade, tumor volume, Eastern Cooperative Oncology Group status, and recurrence status. Propensity score matching analysis revealed that the SBRT group had better IFC (3-year IFC of 77.5% vs 55.6%; P = .007) and OS (3-year OS of 55.0% vs 13.0%; P < .001) than the TACE group. For recurrent HCC, the SBRT group exhibited superior IFC (3-year IFC of 75% vs 57.5%; P = .022) and OS (3-year OS of 58.3% vs 5.9%; P < .001) compared with the TACE group. However, there was no difference in IFC or OS between TACE and SBRT for patients with newly diagnosed HCC. CONCLUSIONS: SBRT has better IFC and OS rates than TACE in patients with medium-sized HCC, particularly for recurrent cases, which warrants prospective randomized controlled trials of TACE and SBRT.

Treatment outcomes with whole-field versus split-field intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to present our comparison of the clinical outcome of patients with nasopharyngeal carcinoma (NPC) treated with whole-field intensity-modulated radiotherapy (whole-field-IMRT) or split-field-IMRT. METHODS: We retrospectively studied 388 patients with M0 NPC. The median lower neck doses were 50 Gy in 1.35 Gy/fractions for the 240 whole-field-IMRT patients, and 50.4 Gy in 1.8 to 2.0 Gy/fractions for the 148 split-field-IMRT patients. RESULTS: The IMRT technique did not affect the overall survival (OS; P = .077) and locoregional control (P = .231) rates. However, the split-field-IMRT group had more locoregional recurrences at the whole neck (P = .005) but not at the nasopharynx (P = .968) or the lower neck (P = .485). The patients treated with split-field-IMRT (43.2%) had more grade III neck fibrosis than the patients who received whole-field-IMRT (18.3%; P < .001). Only 1 patient had temporal lobe necrosis in our study. CONCLUSION: Our study shows that whole-field-IMRT using a lower dose/fraction for the lower neck results in at least comparable locoregional control and less fibrosis compared to conventional fraction with split-field-IMRT.

Association Between Migraine and Breast Cancer Risk: A Population-Based Cohort Study and Literature Review.

Objective: Previous case-control studies have suggested that women with migraine have lower risk of developing breast cancer, but conflicting results were noted in cohort studies. We investigated the association between migraine and breast cancer incidence in a nationwide population-based cohort study. Methods: We identified 25,606 women with migraine between 2000 and 2013 from the National Health Insurance Research Database in Taiwan. Each migraineur was randomly frequency matched with four women without migraine by age and index year of migraine diagnosis. Cox's proportional hazard regression analysis was performed to estimate the association between migraine on the risk of developing breast cancer. Results: With a mean follow-up of 7.3 years, 234 and 978 breast malignancies occurred in the migraine cohort and matched cohort, respectively. Migraine was not associated with the risk of breast cancer (adjusted hazard ratio = 1.03, 95% confidence interval = 0.89-1.21). Among women with migraine, independent risk factors for breast cancer included older age, alcohol-related illness, and receipt of a greater number of breast cancer screening examinations, and independent protective factors included the use of antihypertensive agents, statins, and nonsteroidal anti-inflammatory drugs. Further analyses indicated that women with ≥4 medical visits for migraine per year had a significantly greater risk of breast cancer than the matched cohort. Conclusions: Migraine was not associated with a decreased risk of developing breast cancer among Taiwanese women. Further prospective studies on other geographic populations or on the association between migraine frequency and the risk of developing breast cancer are warranted to validate our findings.

Definitive radiotherapy dose escalation with chemotherapy for treating non-metastatic oesophageal cancer.

The locoregional failure rate remains high after concurrent chemoradiotherapy with standard-dose radiotherapy (RT, 50-50.4 Gy) for oesophageal cancer (EC). This retrospective study evaluated whether RT dose escalation was effective among 115 consecutive patients with non-metastatic EC (July 2003 to November 2016). Forty-four patients received an RT dose of <66 Gy and 71 patients received ≥66 Gy, with most patients receiving concurrent cisplatin plus fluorouracil. The median follow-up was 12 months for all patients (52 months for 18 surviving patients). The ≥66 Gy group had significantly higher 3-year rates of overall survival (17.9% vs. 32.1%, p = 0.026) and local progression-free survival (46.1% vs. 72.1%, p = 0.005), but not disease progression-free survival (11.4% vs. 21.9%, p = 0.059) and distant metastasis-free survival (49% vs. 52.6%, p = 0.852). The ≥66 Gy group also had significantly better 5-year overall survival compared with 41.4-65.9 Gy. The only significant difference in treatment-related toxicities involved acute dermatitis (7% vs. 28%, p = 0.009). Inferior overall survival was associated with poor performance status, clinical N2-3 stage and not receiving maintenance chemotherapy. In conclusion, patients with inoperable EC experienced better survival outcomes and acceptable toxicities if they received higher dose RT (≥66 Gy) rather than lower dose RT (<66 Gy).

Association between nasopharyngeal carcinoma and risk of optic neuropathy: A population-based cohort study.

BACKGROUND: The purpose of this study was to assess the predictive factors of optic neuropathy among patients with nasopharyngeal carcinoma (NPC). METHODS: The analysis included 16 297 patients with NPC and 65 187 controls. Each patient with NPC was randomly frequency-matched with 4 individuals without NPC by age, sex, and index year. Cox proportional hazard models were applied to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) of optic neuropathy development associated with NPC. RESULTS: The risk of optic neuropathy was significantly higher in the NPC cohort (adjusted HR [aHR] 3.42; 95% CI 2.85-4.09; P < .001). Independent risk factors for optic neuropathy among patients with NPC included stroke (aHR 1.7; 95% CI 1.07-2.7; P = .03) and receipt of chemotherapy (aHR 1.55; 95% CI 1.17-2.06; P = .002). CONCLUSION: The risk of optic neuropathy was significantly higher in patients with NPC than in the general population.

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

BACKGROUND: The purpose of this study was to assess the incidence and risk of depressive disorder among patients with head and neck cancer. METHODS: We identified 48 548 patients from the National Health Insurance Research Database (NHIRD) in Taiwan who were newly diagnosed with head and neck cancer between 2000 and 2010. Each patient was randomly frequency-matched with an individual without head and neck cancer, based on index year, sex, age, occupation category, urbanization level, monthly income, and comorbidities. The Cox proportional Registry of Catastrophic Illnesses Patient Database regression analysis was performed to estimate the effect of head and neck cancer on the risk of depressive disorder. RESULTS: Patients with head and neck cancer had a significantly higher risk of depressive disorder than the matched cohort (adjusted hazard ratio [HR] 3.32; 95% confidence interval [CI] 3.05-3.61), with the highest risk seen in the hypopharynx and oropharynx. CONCLUSION: Patients with head and neck cancer had >3 times the incidence of depressive disorder, relative to the comparison group. Psychological evaluation and support are essential in head and neck cancer survivors.

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 second primary malignancies among patients with prostate cancer: A population-based cohort study.

PURPOSE: The rising incidence and life expectancy associated with prostate cancer (PCa) has led to increasing interest in predicting the risk of second primary malignancies (SPMs) among PCa survivors, although data regarding SPMs after PCa are controversial. METHODS: We identified 30,964 patients from the National Health Insurance Research Database in Taiwan who had newly diagnosed PCa between 2000 and 2010. Each patient was randomly frequency-matched with an individual without PCa, based on age, comorbidity, and index year. Competing-risks regression models were used to estimate subhazard ratios (SHRs) of SPMs development associated with PCa. The Bonferroni adjustment was used in multiple comparisons. RESULTS: Men with PCa had a trend of lower risk of developing overall SPMs compared to those without PCa (adjusted SHR = 0.94, 99.72% confidence interval [CI] = 0.89-1.00, p = 0.06). The risks of lung and liver cancer were significantly lower. In contrast, these patients had a significantly higher risk of thyroid cancer. There is a trend for a higher risk of developing SPMs in the urinary bladder and rectum/anus. Further analyses indicated that PCa patients who received radiation therapy (RT) had an increased risk of overall SPMs, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer compared with those who did not receive RT. CONCLUSION: Men with PCa tended to have a lower risk of SPMs, but a significantly higher risk of subsequent thyroid cancer. Continued cancer surveillance is required among PCa survivors, especially in specific sites and in individuals who received RT.

Lower Urinary Tract Infection and Subsequent Risk of Prostate Cancer: A Nationwide Population-Based Cohort Study.

PURPOSE: We investigated whether lower urinary tract infection (LUTI), including cystitis or urethritis, is associated with an increased risk of developing prostate cancer (PCa), in a nationwide population-based cohort study. METHODS: We identified 14,273 men newly diagnosed with LUTI (9347 with cystitis, and 4926 with urethritis) between 1998 and 2011, from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with 4 men without LUTI, based on age and index year of diagnosis. Cox's proportional hazard regression analysis was performed to estimate the effect of LUTI on the PCa risk. RESULTS: The risk of developing PCa was significantly higher in the cystitis cohort (adjusted HR = 1.46, 95% CI = 1.20-1.78) and in the urethritis cohort (adjusted HR = 1.72, 95% CI = 1.26-2.34) than in the group without LUTI. Further analyses indicated that patients with more than 5 medical visits for LUTI per year had a significantly greater risk of developing PCa. CONCLUSION: We found that cystitis or urethritis may play an etiological role in the development of PCa in Taiwanese men, particularly in those with repeated medical visits for cystitis or urethritis. Further studies are warranted on the association between LUTI and PCa in other countries, particularly where the prevalence of PCa is high.

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.

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

The 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.

Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization.

BACKGROUND: The role of stereotactic ablative radiotherapy (SABR) in patients with hepatocellular carcinoma (HCC) who are refractory to or unsuitable for transarterial chemoembolization remains unclear. We examined the efficacy and safety of Cyberknife SABR and its effect on survival in this group of HCC patients. MATERIALS AND METHODS: From June 2008 to June 2011, 53 patients with 68 tumors of unresectable HCC were treated using Cyberknife SABR. The tumors measured 1.1-13 cm (median, 4.3 cm). The median prescribed dose was 40 Gy in four to five fractions over 4-5 consecutive working days. RESULTS: The median follow-up period was 13.1 months for all patients and 18.1 months for the living patients. Objective responses were observed in 48 of 67 tumors (71.6%), including 22 tumors (32.8%) with complete responses. The 1- and 2-year in-field failure-free rate was 73.3 and 66.8%, respectively. Out-field intrahepatic recurrence was the main cause of treatment failure (28/52 patients). The median survival time was 20.0 months, and the 1- and 2-year overall survival rate was 70.1 and 45.4%, respectively. Multivariable analysis showed that Eastern Cooperative Oncology Group performance status (≤1 vs. >1) and tumor response (responder vs. nonresponder) were independent prognostic factors for overall survival. Radiation-induced liver disease, including classic and nonclassic types, developed in five patients (9.4%). Other acute toxicities were generally mild and tolerable. CONCLUSION: Our findings supported the feasibility of SABR as a salvage treatment for HCC when transarterial chemoembolization was ineffective or technically unsuitable. Additional efforts to improve the response rate and reduce out-field recurrence are required.

Stereotactic body radiation therapy in recurrent hepatocellular carcinoma.

PURPOSE: To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4-5 fractions over 4-5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. RESULTS: The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. CONCLUSION: SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.