Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Predicting stereotactic radiosurgery outcomes with multi-observer qualitative appearance labelling versus MRI radiomics.

Qualitative observer-based and quantitative radiomics-based analyses of T1w contrast-enhanced magnetic resonance imaging (T1w-CE MRI) have both been shown to predict the outcomes of brain metastasis (BM) stereotactic radiosurgery (SRS). Comparison of these methods and interpretation of radiomics-based machine learning (ML) models remains limited. To address this need, we collected a dataset of n = 123 BMs from 99 patients including 12 clinical features, 107 pre-treatment T1w-CE MRI radiomic features, and BM post-SRS progression scores. A previously published outcome model using SRS dose prescription and five-way BM qualitative appearance scoring was evaluated. We found high qualitative scoring interobserver variability across five observers that negatively impacted the model's risk stratification. Radiomics-based ML models trained to replicate the qualitative scoring did so with high accuracy (bootstrap-corrected AUC = 0.84-0.94), but risk stratification using these replicated qualitative scores remained poor. Radiomics-based ML models trained to directly predict post-SRS progression offered enhanced risk stratification (Kaplan-Meier rank-sum p = 0.0003) compared to using qualitative appearance. The qualitative appearance scoring enabled interpretation of the progression radiomics-based ML model, with necrotic BMs and a subset of heterogeneous BMs predicted as being at high-risk of post-SRS progression, in agreement with current radiobiological understanding. Our study's results show that while radiomics-based SRS outcome models out-perform qualitative appearance analysis, qualitative appearance still provides critical insight into ML model operation.

Dual-center validation of using magnetic resonance imaging radiomics to predict stereotactic radiosurgery outcomes.

Background: MRI radiomic features and machine learning have been used to predict brain metastasis (BM) stereotactic radiosurgery (SRS) outcomes. Previous studies used only single-center datasets, representing a significant barrier to clinical translation and further research. This study, therefore, presents the first dual-center validation of these techniques. Methods: SRS datasets were acquired from 2 centers (n = 123 BMs and n = 117 BMs). Each dataset contained 8 clinical features, 107 pretreatment T1w contrast-enhanced MRI radiomic features, and post-SRS BM progression endpoints determined from follow-up MRI. Random decision forest models were used with clinical and/or radiomic features to predict progression. 250 bootstrap repetitions were used for single-center experiments. Results: Training a model with one center's dataset and testing it with the other center's dataset required using a set of features important for outcome prediction at both centers, and achieved area under the receiver operating characteristic curve (AUC) values up to 0.70. A model training methodology developed using the first center's dataset was locked and externally validated with the second center's dataset, achieving a bootstrap-corrected AUC of 0.80. Lastly, models trained on pooled data from both centers offered balanced accuracy across centers with an overall bootstrap-corrected AUC of 0.78. Conclusions: Using the presented validated methodology, radiomic models trained at a single center can be used externally, though they must utilize features important across all centers. These models' accuracies are inferior to those of models trained using each individual center's data. Pooling data across centers shows accurate and balanced performance, though further validation is required.

Association of Primary Tumor Volume With Survival in Patients With T3 Glottic Cancer Treated With Radiotherapy: A Study of the Canadian Head & Neck Collaborative Research Initiative.

Importance: The association of primary tumor volume with outcomes in T3 glottic cancers treated with radiotherapy with concurrent chemotherapy remains unclear, with some evidence suggesting worse locoregional control in larger tumors. Objective: To evaluate the association of primary tumor volume with oncologic outcomes in patients with T3 N0-N3 M0 glottic cancer treated with primary (chemo)radiotherapy in a large multi-institutional study. Design, Setting, and Participants: This multi-institutional retrospective cohort study involved 7 Canadian cancer centers from 2002 to 2018. Tumor volume was measured by expert neuroradiologists on diagnostic imaging. Clinical and outcome data were extracted from electronic medical records. Overall survival (OS) and disease-free survival (DFS) outcomes were assessed with marginal Cox regression. Laryngectomy-free survival (LFS) was modeled as a secondary analysis. Patients diagnosed with cT3 N0-N3 M0 glottic cancers from 2002 to 2018 and treated with curative intent intensity-modulated radiotherapy (IMRT) with or without chemotherapy. Overall, 319 patients met study inclusion criteria. Exposures: Tumor volume as measured on diagnostic imaging by expert neuroradiologists. Main Outcomes and Measures: Primary outcomes were OS and DFS; LFS was assessed as a secondary analysis, and late toxic effects as an exploratory analysis determined before start of the study. Results: The mean (SD) age of participants was 66 (12) years and 279 (88%) were men. Overall, 268 patients (84%) had N0 disease, and 150 (47%) received concurrent systemic therapy. The mean (SD) tumor volume was 4.04 (3.92) cm3. With a mean (SD) follow-up of 3.85 (3.04) years, there were 91 (29%) local, 35 (11%) regional, and 38 (12%) distant failures. Increasing tumor volume (per 1-cm3 increase) was associated with significantly worse adjusted OS (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11) and DFS (HR, 1.04; 95% CI, 1.01-1.07). A total of 62 patients (19%) underwent laryngectomies with 54 (87%) of these within 800 days after treatment. Concurrent systemic therapy was associated with improved LFS (subdistribution HR, 0.63; 95% CI, 0.53-0.76). Conclusions and Relevance: Increasing tumor volumes in cT3 glottic cancers was associated with worse OS and DFS, and systemic therapy was associated with improved LFS. In absence of randomized clinical trial evidence, patients with poor pretreatment laryngeal function or those ineligible for systemic therapy may be considered for primary surgical resection with postoperative radiotherapy.

The Impact of Surgical Resectability on Outcomes for Patients Undergoing Primary Radiation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer.

PURPOSE: Primary radiation therapy with or without chemotherapy (RT/CRT) is the most common treatment for oropharyngeal squamous cell carcinomas (OPSCC), but there has been an increase in transoral surgery (TOS) for T1-2 tumors. Because only a subset of T1-2 tumors are TOS-favorable, nonrandomized comparisons between RT/CRT and TOS could be confounded by indication. We aimed to compare outcomes of potential TOS-candidates versus non-TOS candidates, among patients who underwent RT/CRT for early T-stage OPSCC. METHODS AND MATERIALS: For patients treated with RT/CRT for early-stage human papilloma virus positive OPSCC between 2014 and 2018, pretreatment imaging was reviewed by 3 head and neck surgeons, blinded to outcomes, to assess primary-site appropriateness for TOS, and extracapsular extension (ECE) was scored by a head and neck neuroradiologist. We compared outcomes based on surgical favorability pertaining to (1) the primary site tumor alone and (2) the primary site and an absence of ECE. Kaplan-Meier estimates for overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared using the log-rank test, with Cox regression used for multivariable modeling. RESULTS: One hundred and forty-three patients were evaluated, of which 121 were male (84.6%), the median age was 59.4 years, and all of them were p16 positive (100%). The primary site was TOS-favorable in 115 of 143 (80.4%). Patients with TOS-favorable primary site experienced superior 5-year OS (89.8% vs 71.2%, P = .017), DSS (90.4% vs 63.4%, P = .022), and RFS (83% vs 49.4%, P = .04) compared with TOS-unfavorable patients. Similarly, patients with a TOS-favorable primary site and no ECE on imaging 101 of 143 (70.6%), had improved OS, DSS, and RFS (P < .05) compared with TOS-unfavorable patients. CONCLUSIONS: In this first study to assess surgical favorability as a prognostic factor among patients with T1/2 p16+ OPSCC, patients with TOS-favorable early-stage OPSCC have better outcomes than TOS-unfavorable patients. This provides valuable prognostic information for patients, and also suggests the risk of confounding by indication in nonrandomized comparisons of treatment modalities.

Utilizing Artificial Intelligence for Head and Neck Cancer Outcomes Prediction From Imaging.

Artificial intelligence (AI)-based models have become a growing area of interest in predictive medicine and have the potential to aid physician decision-making to improve patient outcomes. Imaging and radiomics play an increasingly important role in these models. This review summarizes recent developments in the field of radiomics for AI in head and neck cancer. Prediction models for oncologic outcomes, treatment toxicity, and pathological findings have all been created. Exploratory studies are promising; however, validation studies that demonstrate consistency, reproducibility, and prognostic impact remain uncommon. Prospective clinical trials with standardized procedures are required for clinical translation.

Payments and Patient Cost Sharing for Prostate Biopsies According to Image Guidance, Practice Site and Use of Anesthesia.

INTRODUCTION: Use of magnetic resonance imaging for prostate biopsies has increased and more biopsies are performed in nonoffice based settings. These changes will likely impact payments related to prostate biopsies. METHODS: Using private insurance claims from 2009 to 2015 we identified men who underwent transrectal ultrasound guided (CPT 55700) or transperineal (CPT 55706) prostate biopsies. We assumed any magnetic resonance imaging of the pelvis within 3 months prior to biopsy was for image based guidance. We assigned biopsy site as being performed in the office, ambulatory surgical center or hospital. Use of anesthesia was based on CPT codes 00100-01999. Our primary outcome was aggregate payments for anesthesia, pathology, imaging and procedural services. We also studied patient out-of-pocket costs. Multivariable regression was used to generate predicted payments based on magnetic resonance imaging performance, anesthesia and site of biopsy. RESULTS: We identified 304,388 biopsy episodes, of which 2.2% were magnetic resonance imaging guided and 0.7% were transperineal. Median cost of magnetic resonance imaging guided biopsies was greatest at $4,396 (IQR $2,784-$7,127) compared to the costs of transperineal and transrectal ultrasound guided biopsies. Imaging accounted for the greatest share of magnetic resonance imaging guided biopsy costs (median $1,704, IQR $975-$3,043). Magnetic resonance imaging guided biopsies in a hospital with anesthesia had the highest cost at $5,832 per episode (95% CI $5,732-$5,934). There was a fivefold difference in patient cost sharing between the least expensive (transperineal, office and no anesthesia $168) and most expensive (magnetic resonance imaging guided, ambulatory surgical center with anesthesia $891) modality. CONCLUSIONS: Total and out-of-pocket costs for prostate biopsies vary substantially based on modality, location and anesthesia use.

Combined nicotine patch with gum versus nicotine patch alone in smoking cessation in Hong Kong primary care clinics: a randomised controlled trial.

BACKGROUND: The prevalence of daily cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however, smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher with combined NRT than single NRT, although local data on safety and benefits of combined NRT are lacking. The aim of this study is to compare the effectiveness of combined NRT with single NRT among HK Chinese. METHODS: This is a one-year, two-arm, parallel randomised trial. Five hundred sixty smokers, who smoked ≥10 cigarettes/day for ≥1 year, were randomized to combined and single NRT. Combined NRT group received counseling and nicotine patch & gum. Single NRT group received counselling and nicotine patch. Primary outcome was abstinence rate measured as self-reported 7-day point prevalence with CO validated at 52 weeks. Secondary outcomes included smoking abstinence rates at 4, 12, & 26 weeks. Crude odds ratio and p-value were reported from logistic regression without adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age, sex, baseline CO and clusters. RESULTS: Abstinence rates at 4, 12, 26 and 52 weeks were all higher in the combined NRT group (35.8, 21.9, 16.8, 20.1%) compared with the single NRT group (28, 16.8, 11.2, 14.3%). At 4 weeks, combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.00 to 2.05) than the single NRT group. From GEE analysis, combined NRT group had a significantly higher abstinence rate (23.6%) than the single NRT group (17.6%) across repeated measures at all-time points. Combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.15 to 1.77). No significant difference in the side effect profile was detected between groups. CONCLUSIONS: Smokers given 8 weeks of combined NRT were more likely to quit smoking at 4, 12, 26 and 52 weeks compared with single NRT. Combined NRT was as well tolerated as single NRT and it should be further promoted in our community. TRIAL REGISTRATION: NCT03836560 from ClinicalTrial.gov , 9 Feb 2019.

The prionlike domain of FUS is multiphosphorylated following DNA damage without altering nuclear localization.

FUS (fused in sarcoma) is an abundant, predominantly nuclear protein involved in RNA processing. Under various conditions, FUS functionally associates with RNA and other macromolecules to form distinct, reversible phase-separated liquid structures. Persistence of the phase-separated state and increased cytoplasmic localization are both hypothesized to predispose FUS to irreversible aggregation, which is a pathological hallmark of subtypes of amyotrophic lateral sclerosis and frontotemporal dementia. We previously showed that phosphorylation of FUS's prionlike domain suppressed phase separation and toxic aggregation, proportionally to the number of added phosphates. However, phosphorylation of FUS's prionlike domain was previously reported to promote its cytoplasmic localization, potentially favoring pathological behavior. Here we used mass spectrometry and human cell models to further identify phosphorylation sites within FUS's prionlike domain, specifically following DNA-damaging stress. In total, 28 putative sites have been identified, about half of which are DNA-dependent protein kinase (DNA-PK) consensus sites. Custom antibodies were developed to confirm the phosphorylation of two of these sites (Ser-26 and Ser-30). Both sites were usually phosphorylated in a subpopulation of cellular FUS following a variety of DNA-damaging stresses but not necessarily equally or simultaneously. Importantly, we found DNA-PK-dependent multiphosphorylation of FUS's prionlike domain does not cause cytoplasmic localization.

The Clinical Course of Patients With Prostate-Specific Antigen ≥100 ng/ml: Insight Into a Potential Population for Targeted Prostate-Specific Antigen Screening.

OBJECTIVE: To characterize men presenting to a tertiary care safety-net hospital with prostate-specific antigen (PSA) values ≥100 ng/mL and to identify a potential population for targeted PSA screening. MATERIALS AND METHODS: Retrospective review of 100 randomly selected patients of a total of 204 who presented to Grady Memorial Hospital from 2004 to 2011 with initial PSA ≥100 ng/mL was performed. Demographics, disease characteristics, and survival status were obtained via the Tumor Registry and a combination of electronic medical records and older paper charts, with missing data from paper charts excluded on analyses. RESULTS: Sixty-five patients were newly diagnosed with prostate cancer on presentation and 35 were previously diagnosed. Median PSA at presentation was 405.5 ng/mL (minimum, 100 and maximum, 7805), 81% had metastatic disease, and 94% had Gleason ≥7. Median Cancer of the Prostate Risk Assessment score was 8. Median age at presentation was 67.4 years (minimum, 40.8 and maximum, 90.6). Eighty-nine percent of patients were African American, 24% lived alone, 12% were homeless or incarcerated, 51% were insured by Medicare or Medicaid, and 47% were uninsured. Only 1% had human immunodeficiency virus, 19% had diabetes, and 13% had chronic kidney disease. Of the 65 newly diagnosed patients, only 23% had ever been screened and 9% were previously biopsied. Median time from presentation to death was 17.8 months (minimum, 0.16 and maximum, 107.1). CONCLUSION: Among men presenting with PSA ≥100 ng/ml at a safety-net hospital, the majority were African American, of lower socioeconomic status, and had metastatic disease. Uniform absence of prostate cancer screening may expose greater numbers of at-risk men to similar outcomes. Discussion is needed regarding targeted PSA screening in higher risk, vulnerable patients.

Cost considerations for systemic therapy for patients with advanced genitourinary malignancies.

The rising cost of health care in the United States has been the focus of intense debate within the medical, legal, and legislative arenas, with the cost of cancer care representing an important component. Cost effectiveness is not always easy to define, and there is no standard metric in assessing this measure related to cancer therapies. Significant controversy surrounds exactly what is the appropriate cost per added year of life. This review examines cost, effectiveness, and comparative cost effectiveness of novel systemic therapies for patients with urologic malignancies. Cancer 2018;124:2897-905. © 2018 American Cancer Society.

Computed tomography interobserver agreement in the assessment of aneurysmal subarachnoid hemorrhage and predictors for clinical outcome.

BACKGROUND: The severity of aneurysmal subarachnoid hemorrhage (SAH) is often assessed by the clinical state of the patient on presentation, but radiological evaluation of the extent of hemorrhage has rarely been examined in the literature. Several CT scan based grading systems exist yet only a few studies have investigated interobserver agreement. We evaluated five radiological grading systems and assessed their clinical value for early prognostication. METHODOLOGY: This was a retrospective study of patients diagnosed with aneurysmal SAH with a CT scan performed within 72 hours of symptom onset. Four independent observers, blinded to patient outcome, evaluated each scan using the five grading systems. A separate assessor determined 6 month outcome from clinical records. The primary outcome was interobserver agreement for each grading system using the Fleiss κ statistic. The secondary endpoint was the 6 month modified Rankin Scale score, with poor outcome defined as a score of 4-6. RESULTS: 165 patients with a mean age of 59 years were assessed. Interobserver agreement for the Fisher, modified Fisher, Claassen, Barrow Neurological Institute, and Hijdra grading systems were as follows: k=0.53 (moderate), k=0.42 (moderate), k=0.38 (mild), k=0.20 (poor), and k=0.66 (good), respectively. The only independent clinical risk factor for poor outcome was a World Federation of Neurological Surgeons (WFNS) grade of 4 or 5 (adjusted OR 6.55; p<0.05). After adjusting for confounders, Fisher grade 4 (adjusted OR 17.84), modified Fisher grade 4 (adjusted OR 5.65), and Hijdra grade 3 (adjusted OR 3.34) were associated with poor outcome. Receiver operator characteristic analysis revealed that the Hijdra grading system (area under the curve=0.76) was more predictive of outcome compared with the Fisher and modified Fisher systems. A Hijdra cut-off score of 22 was associated with poor outcome (adjusted OR 5.92). CONCLUSIONS: The Hijdra grading system had the best interobserver agreement and was a better independent early predictor for 6 month clinical outcome than the other systems. A Hijdra score ≥22 was associated with poor outcome.