Novel Inflammasome-Based Risk Score for Predicting Survival and Efficacy to Immunotherapy in Early-Stage Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICI) for early-stage non-small cell lung cancer (NSCLC) have been approved to improve outcomes and reduce recurrence. Biomarkers for patient selection are needed. In this paper, we proposed an inflammasome-based risk score (IRS) system for prognosis and prediction of ICI response for early-stage NSCLC. Cox regression analysis was used to identify significant genes (from 141 core inflammasome genes) for overall survival (OS) in a microarray discovery cohort (n = 467). IRS was established and independently validated by other datasets (n = 1320). We evaluated the inflammasome signaling steps based on five gene sets, which were IL1B-, CASP-1-, IL18-, GSDMD-, and inflammasome-regulated genes. Gene set enrichment analysis, the Kaplan-Meier curve, receiver operator characteristic with area under curve (AUC) analysis, and advanced bioinformatic tools were used to confirm the ability of IRS in prognosis and classification of patients into ICI responders and non-responders. A 30-gene IRS was developed, and it indicated good risk stratification at 10-year OS (AUC = 0.726). Patients were stratified into high- and low-risk groups based on optimal cutoff points, and high-risk IRS had significantly poorer OS and relapse-free survival. In addition, the high-risk group was characterized by an inflamed immunophenotype and higher proportion of ICI responders. Furthermore, expression of SLAMF8 was the key gene in IRS and indicated good correlation with biomarkers associated with immunotherapy. It could serve as a therapeutic target in the clinical setting of immunotherapy.

Risk of ocular complications following radiation therapy in patients with nasopharyngeal carcinoma.

OBJECTIVE: To examine the risk of ocular complications following radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: We adopted 1:1 propensity score matching and identified an NPC cohort (n = 736) and a comparison cohort (n = 736) that comprised non-NPC head and neck cancer patients who received radiotherapy in the National Health Insurance Research Database from 1997 to 2010. The follow-up period was terminated upon developing ocular complications (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]360-379) or on December 31, 2010. RESULTS: After adjusting for the confounding factors of the study, the NPC cohort had a higher adjusted hazard ratio (HR) for developing ocular complications than the comparison cohort (adjusted HR = 2.786, 95% confidence interval [CI] = 1.805-4.112, P < 0.001). The NPC cohort was associated with a significantly higher risk of developing ocular complications compared with the comparison cohort within 12 and after 24 months of follow-up (P < 0.05). The most common associated ocular complications were optic nerve disorder and retinopathy. CONCLUSIONS: Patients with NPC might be at higher risk of developing ocular complications after radiotherapy than non-NPC head and neck cancer patients in Taiwan. Either further investigation or routine assessments by ophthalmological physician is recommended. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1270-1277, 2020.

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.

Risk of gastric cancer following percutaneous endoscopic gastrostomy: A nationwide population-based cohort study.

OBJECTIVES: To investigate whether percutaneous endoscopic gastrostomy (PEG) tube placement is associated with increased risk of gastric cancer. METHODS: We conducted a nationwide population-based retrospective study in Taiwan. Inpatient data from 1997 to 2010 were collected from Taiwan National Health Insurance Research Database. Patients with age less than 20 years; those with histories of PEG before 2000; those with histories of cancers; and those diagnosed with gastric cancer before or within 6 months of the first PEG procedure were excluded. Finally, 3505 patients who underwent PEG were included (PEG cohort), along with 7010 randomly-selected individuals, matched by age, sex, and year of index date, as the control cohort. RESULTS: After adjusting for age, sex, peptic ulcer, gastritis, hypertension, diabetes and coronary artery disease, risk of gastric cancer was significantly higher in the PEG cohort (adjusted hazard ratio, 5.31; 95% confidence interval, 4.12-6.00; p = 0.011). Patients with 2 or more PEG procedures were significantly associated with increasingly developing gastric cancer risk (adjusted hazard ratio, 2.73; 95% confidence interval, 1.91-3.85; p < 0.001). The possible hypothesis may be due to chronic inflammation caused by chemical and physical conditions of the tube. CONCLUSIONS: Patients with PEG might be associated with a greater risk of subsequent gastric cancer in Taiwan. Physicians should be aware of the link when assessing patients with PEG.

Dose escalation via brachytherapy boost for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy and combined chemotherapy.

To investigate if dose escalation using intracavitary brachytherapy (ICBT) improves local control for nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT) and concurrent chemoradiation treatment (CCRT). We retrospectively analyzed 232 patients with Stage T1-3 N0-3 M0 NPC who underwent definitive IMRT with or without additional ICBT boost between 2002 and 2013. For most of the 124 patients who had ICBT boost, the additional brachytherapy was given as 6 Gy in 2 fractions completed within 1 week after IMRT of 70 Gy. CCRT with or without adjuvant chemotherapy was used for 176 patients, including 88 with and 88 without ICBT boost, respectively. The mean follow-up time was 63.1 months. The 5-year overall survival and local control rates were 81.5% and 91.5%, respectively. ICBT was not associated with local control prediction (P = 0.228). However, in a subgroup analysis, 75 T1 patients with ICBT boost had significantly better local control than the other 71 T1 patients without ICBT boost (98.1% vs 85.9%, P = 0.020), despite having fewer patients who had undergone chemotherapy (60.0% vs 76.1%, P = 0.038). Multivariate analysis showed that both ICBT (P = 0.029) and chemotherapy (P = 0.047) influenced local control for T1 patients. Our study demonstrated that dose escalation with ICBT can improve local control of the primary tumor for NPC patients with T1 disease treated with IMRT, even without chemotherapy.

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.

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.