Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Incidence and time trends of herpes zoster among patients with head and neck cancer who did and did not undergo radiotherapy: A population-based cohort study.

PURPOSE: This study aimed to determine the risk and time trends of herpes zoster among patients with head and neck cancer, with or without radiotherapy. METHODS: A total of 2160 patients with head and neck cancer were enrolled. The radiotherapy and non- radiotherapy cohorts were frequency-matched at a 1:1 ratio according to sex, age, and index date. Moreover, 1080 matched non-cancer individuals were considered normal controls. Data were obtained from the National Health Insurance Research Database and Cancer Registry. The primary end point was the incidence of herpes zoster, and the adjusted confounding factors were age, sex, comorbidities, oncological surgery, and chemotherapy. RESULTS: The incidence of herpes zoster was higher in cancer patients than in non-cancer individuals but did not significantly differ (13.67 vs. 8.06 per 1,000 person-years, p = 0.18). The risk of herpes zoster was significantly higher in the radiotherapy cohort than in the non-radiotherapy cohort (18.55 vs. 9.06 per 1,000 person-years, p = 0.03). The 5-year incidence rates in the radiotherapy and non-radiotherapy cohorts were 8.9% and 5%, respectively (p < 0.0001). Survival analysis indicated there was no immortal time bias. The time trends in the radiotherapy cohort persistently showed a high risk within the first 2 years, which decreased thereafter. Only patients with comorbid rheumatoid arthritis showed a significantly high risk of herpes zoster (p = 0.02). Oncological surgery and chemotherapy had no impact on the development of herpes zoster. CONCLUSIONS: This nationwide population-based study showed that patients with head and neck cancer receiving radiotherapy are at an increased risk of herpes zoster. Health care professionals should pay more attention to this vulnerable group to improve their quality of life.

Radiotherapy combined with chemotherapy increases the risk of herpes zoster in patients with gynecological cancers: a nationwide cohort study.

OBJECTIVE: This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study. METHODS: Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 non-cancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders. RESULTS: The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter. CONCLUSION: This population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.

Predicting pathological complete response in rectal cancer after chemoradiotherapy with a random forest using 18F-fluorodeoxyglucose positron emission tomography and computed tomography radiomics.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the standard treatment for patients with locally advanced rectal cancer. This study developed a random forest (RF) model to predict pathological complete response (pCR) based on radiomics derived from baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography (PET)/computed tomography (CT). METHODS: This study included 169 patients with newly diagnosed rectal cancer. All patients received 18F[FDG]-PET/CT, NCRT, and surgery. In total, 68 radiomic features were extracted from the metabolic tumor volume. The numbers of splits in a decision tree and trees in an RF were determined based on their effects on predictive performance. Receiver operating characteristic curve analysis was performed to evaluate predictive performance and ascertain the optimal threshold for maximizing prediction accuracy. RESULTS: After NCRT, 22 patients (13%) achieved pCR, and 42 features that could differentiate tumors with pCR were used to construct the RF model. Six decision trees and seven splits were suitable. Accordingly, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 81.8%, 97.3%, 81.8%, 97.3%, and 95.3%, respectively. CONCLUSIONS: By using an RF, we determined that radiomics derived from baseline 18F[FDG]-PET/CT could accurately predict pCR in patients with rectal cancer. Highly accurate and predictive values can be achieved but should be externally validated.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. METHODS: We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. RESULTS: A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46-2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12-1.54), age 40-59 years (AHR = 1.49, 95%CI: 1.21-1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08-3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05-4.77) and without (AHR = 1.77, 95%CI: 1.46-2.15) sleep apnea had an increased risk of NAFLD. CONCLUSIONS: Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

A topology-based method to mitigate the dosimetric uncertainty caused by the positional variation of the boost volume in breast conservative radiotherapy.

BACKGROUND: To improve local control rate in patients with breast cancer receiving adjuvant radiotherapy after breast conservative surgery, additional boost dose to the tumor bed could be delivered simultaneously via the simultaneous integrated boost (SIB) modulated technique. However, the position of tumor bed kept changing during the treatment course as the treatment position was aligned to bony anatomy. This study aimed to analyze the positional uncertainties between bony anatomy and tumor bed, and a topology-based approach was derived to stratify patients with high variation in tumor bed localization. METHODS: Sixty patients with early-stage breast cancer or ductal carcinoma in situ were enrolled. All received adjuvant whole breast radiotherapy with or without local boost via SIB technique. The delineation of tumor bed was defined by incorporating the anatomy of seroma, adjacent surgical clips, and any architectural distortion on computed tomography simulation. A total of 1740 on-board images were retrospectively analyzed. Positional uncertainty of tumor bed was assessed by four components: namely systematic error (SE), and random error (RE), through anterior-posterior (AP), cranial-caudal (CC), left-right (LR) directions and couch rotation (CR). Age, tumor location, and body-mass factors including volume of breast, volume of tumor bed, breast thickness, and body mass index (BMI) were analyzed for their predictive role. The appropriate margin to accommodate the positional uncertainty of the boost volume was assessed, and the new plans with this margin for the tumor bed was designed as the high risk planning target volume (PTV-H) were created retrospectively to evaluate the impact on organs at risk. RESULTS: In univariate analysis, a larger breast thickness, larger breast volume, higher BMI, and different tumor locations correlated with a greater positional uncertainty of tumor bed. However, BMI was the only factor associated with displacements of surgical clips in the multivariate analysis and patients with higher BMI were stratified as high variation group. When image guidance was aligned to bony structures, the SE and RE of clip displacement were consistently larger in the high variation group. The corresponding PTV-H margins for the high- and low-variation groups were 7, 10, 10 mm and 4, 9, 6 mm in AP, CC, LR directions, respectively. The heart dose between the two plans was not significantly different, whereas the dosimetric parameters for the ipsilateral lung were generally higher in the new plans. CONCLUSIONS: In patients with breast cancer receiving adjuvant radiotherapy, a higher BMI is associated with a greater positional uncertainty of the boost tumor volume. More generous margin should be considered and it can be safely applied through proper design of beam arrangement with advanced treatment techniques.