Publications by authors named "Henry S Park"

120 Publications

Linear accelerator-based single-fraction stereotactic radiosurgery versus hypofractionated stereotactic radiotherapy for intact and resected brain metastases up to 3 cm: A multi-institutional retrospective analysis.

J Radiosurg SBRT 2021 ;7(3):179-187

Tufts University School of Medicine, Department of Radiation Oncology, Boston, MA 02111, USA.

Introduction: Single-fraction stereotactic radiosurgery (SF-SRS) is typically used to provide local control of brain metastases. Recently, hypofractionated stereotactic radiotherapy (HF-SRT) has been utilized for large brain metastases. Data comparing these two modalities are limited for brain metastases ≤3 cm.

Methods: Patients with brain metastases receiving linear accelerator-based SF-SRS or HF-SRT were identified at three institutions. Local progression-free survival (LPFS), intracranial progression-free survival (ICPFS), overall survival (OS), and radionecrosis-free survival (RNFS) were determined from time of treatment.

Results: 108 patients (76 intact, 32 resected) with 184 brain metastases (142 intact, 42 resected) were included. There were no significant differences between SF-SRS and HF-SRT for intact metastases in 1-year LPFS (62.8% vs. 58.5%, p=0.631), ICPFS (56.9% vs. 55.3%, p=0.300), and OS (71.6% vs. 70.6%, p=0.096), or for resected metastases in 1-year LPFS (67.3% vs. 57.8%, p=0.288), ICPFS (64.8% vs. 57%, p=0.291), and OS (64.8% vs. 66.1%, p=0.603). There were also no significant differences in 1-year RNFS between SF-SRS and HF-SRT (92% vs. 92%, p=0.325).

Conclusions: There were no significant differences in LPFS, ICPFS, OS, and RNFS between SF-SRS and HF-SRT for brain metastases ≤3 cm suggesting SF-SRS may be preferred due to similar outcomes and reduced number of fractions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055233PMC
January 2021

Association of epigenetic age acceleration with risk factors, survival, and quality of life in patients with head and neck cancer.

Int J Radiat Oncol Biol Phys 2021 Apr 18. Epub 2021 Apr 18.

Emory University School of Nursing.

Purpose: Epigenetic age acceleration (EAA) is robustly linked with mortality and morbidity. This study examined risk factors of EAA and its association with overall survival (OS), progression-free survival (PFS), and quality of life (QOL) in patients with head and neck cancer (HNC) receiving radiotherapy.

Methods And Materials: Patients without distant metastasis were enrolled and followed before and end of radiotherapy, and 6-months and 12-months post-radiotherapy. EAA was calculated with DNAmPhenoAge at all four times. Risk factors included demographics, lifestyle, clinical characteristics, treatment-related symptoms, and blood biomarkers. Survival data were collected until August 2020; QOL was measured using Functional Assessment of Cancer Therapy-HNC.

Results: Increased comorbidity, HPV-unrelated, and severer treatment-related symptoms were associated with higher EAA (p=0.03 to <0.001). A non-linear association (quadratic) between body mass index (BMI) and EAA was observed: decreased BMI (when BMI<35,p=0.04) or increased BMI (when BMI≥35,p=0.01), was linked to higher EAA. Increased EAA (per year) was associated with worse OS (hazard ratio (HR)=1.11,95% CI=[1.03,1.18],p=0.004; HR=1.10,95% CI=[1.01,1.19], p=0.02, for EAA at 6-months and 12-months post-treatment, respectively), PFS (HR=1.10, 95% CI=[1.02,1.19], p=0.02; HR=1.14, 95% CI=[1.06,1.23], p<0.001; HR=1.08,95% CI=[1.02,1.14], p=0.01, for EAA before, end, and 6-months post-radiotherapy, respectively), and QOL over time (β=-0.61,p=0.001). An average of 3.25-3.33 years of age acceleration across time, which was responsible for 33% to 44% higher HRs of OS and PFS, was observed in those who died or developed recurrences compared to those who did not (all p<0.001).

Conclusion: Compared to demographic and lifestyle factors, clinical characteristics were more likely to contribute to faster biological aging in patients with HNC. Acceleration in epigenetic age resulted in more aggressive adverse events including OS and PFS. EAA could be considered as a marker for cancer outcomes, and decelerating aging could improve survival and QOL.
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http://dx.doi.org/10.1016/j.ijrobp.2021.04.002DOI Listing
April 2021

Prevalence of Missing Data in the National Cancer Database and Association With Overall Survival.

JAMA Netw Open 2021 Mar 1;4(3):e211793. Epub 2021 Mar 1.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.

Importance: Cancer registries are important real-world data sources consisting of data abstraction from the medical record; however, patients with unknown or missing data are underrepresented in studies that use such data sources.

Objective: To assess the prevalence of missing data and its association with overall survival among patients with cancer.

Design, Setting, And Participants: In this retrospective cohort study, all variables within the National Cancer Database were reviewed for missing or unknown values for patients with the 3 most common cancers in the US who received diagnoses from January 1, 2006, to December 31, 2015. The prevalence of patient records with missing data and the association with overall survival were assessed. Data analysis was performed from February to August 2020.

Exposures: Any missing data field within a patient record among 63 variables of interest from more than 130 total variables in the National Cancer Database.

Main Outcomes And Measures: Prevalence of missing data in the medical records of patients with cancer and associated 2-year overall survival.

Results: A total of 1 198 749 patients with non-small cell lung cancer (mean [SD] age, 68.5 [10.9] years; 628 811 men [52.5%]), 2 120 775 patients with breast cancer (mean [SD] age, 61.0 [13.3] years; 2 101 758 women [99.1%]), and 1 158 635 patients with prostate cancer (mean [SD] age, 65.2 [9.0] years; 100% men) were included in the analysis. Among those with non-small cell lung cancer, 851 295 patients (71.0%) were missing data for variables of interest; 2-year overall survival was 33.2% for patients with missing data and 51.6% for patients with complete data (P < .001). Among those with breast cancer, 1 161 096 patients (54.7%) were missing data for variables of interest; 2-year overall survival was 93.2% for patients with missing data and 93.9% for patients with complete data (P < .001). Among those with prostate cancer, 460 167 patients (39.7%) were missing data for variables of interest; 2-year overall survival was 91.0% for patients with missing data and 95.6% for patients with complete data (P < .001).

Conclusions And Relevance: This study found that within a large cancer registry-based real-world data source, there was a high prevalence of missing data that were unable to be ascertained from the medical record. The prevalence of missing data among patients with cancer was associated with heterogeneous differences in overall survival. Improvements in documentation and data quality are necessary to make optimal use of real-world data for clinical advancements.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.1793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988369PMC
March 2021

Genomic Characterization of Radiation-Induced Intracranial Undifferentiated Pleomorphic Sarcoma.

Case Rep Genet 2021 8;2021:5586072. Epub 2021 Mar 8.

Department of Neurosurgery, Yale School of Medicine, New Haven 06511, CT, USA.

Intracranial undifferentiated pleomorphic sarcoma remains a rare pathology within the sarcoma literature that may arise primarily or secondary after radiation therapy. Despite first-line treatment with maximal surgical resection, followed by nonstandardized adjuvant chemotherapy/radiation regimens, clinical prognosis remains exceedingly poor. Furthermore, there is a lack of genetic or molecular characterization to guide potential for targeted therapies. We present genomic analysis of a radiation-induced intracranial undifferentiated pleomorphic sarcoma in an 83-year-old woman with notable KIT and PDGFRA alterations. Further similar genomic studies of intracranial pleomorphic sarcoma are needed to develop better therapies for this rare but challenging disease entity.
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http://dx.doi.org/10.1155/2021/5586072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960067PMC
March 2021

Mutational Profile Evaluates Response and Survival to First-Line Chemotherapy in Lung Cancer.

Adv Sci (Weinh) 2021 Feb 30;8(4):2003263. Epub 2020 Dec 30.

Department of Medical Oncology Shanghai Pulmonary Hospital and Thoracic Cancer Institute Tongji University School of Medicine No. 507, Zhengmin Road, Yangpu District Shanghai 200433 P. R. China.

Evaluating the therapeutic response and survival of lung cancer patients receiving first-line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long-term survival of lung cancer patients receiving first-line chemotherapy are discovered. Whole-exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non-small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1-C4). The long-term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed ( < 0.001). NSCLC patients can be divided into three subtypes (S1-S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first-line chemotherapy in lung cancer.
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http://dx.doi.org/10.1002/advs.202003263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887584PMC
February 2021

Evaluation of head and neck soft tissue sarcoma 8th edition pathologic staging system and proposal of a novel stage grouping system.

Oral Oncol 2021 03 8;114:105137. Epub 2021 Jan 8.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA; Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: The AJCC 8th edition issued a dedicated staging system for head and neck soft tissue sarcomas (HN-STS) with 2 and 4 cm tumor cut-off points, as well as a T4 classification based on invasion of adjacent structures. Stage groupings were not provided due to a paucity of data.

Methods: We identified HN-STS patients undergoing primary surgery without neoadjuvant therapy patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used multivariable analysis to examine adverse prognosticators. Then, using, recursive partitioning analysis (RPA), we established a stage grouping system that was externally validated in the National Cancer Database (NCDB).

Results: Multivariable analysis in the SEER cohort (N = 546) demonstrated worsened survival with tumors invading adjacent structures (P < 0.001) and increasing de-differentiation (P < 0.001). There was no prognostic difference based on size for T1-3 tumors; however, when assessed as a continuous variable, a 5 cm tumor size cut-off point was predictive of outcome. RPA generated a stage grouping system with the following five-year overall survival: RPA Stage I (pT1-3N0-1G1-2M0) 71.2%, RPA Stage II (pT4abN0-1G1-2M0/pT1-3N0-1G3-4M0) 53.4%, and RPA Stage III (pT4abN0-1G3-4M0) 17.5%. This was successfully externally validated in the NCDB cohort (P < 0.001).

Conclusions: We confirm the importance of structural invasion and grade and demonstrate that the currently used size cut-off points are not prognostic. We propose a novel stage grouping system. A 5 cm tumor size cut-off point for tumor stage should be further evaluated.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105137DOI Listing
March 2021

Emergency Department Visits for Firearm-Related Injuries among Youth in the United States, 2006-2015.

J Law Med Ethics 2020 12;48(4_suppl):67-73

Victor Lee is at the Department of Therapeutic Radiology at Yale School of Medicine in New Haven, CT. Catherine Camp, M.P.H., is at the Yale Law School in New Haven, CT. Vikram Jairam, M.D., is at the Department of Therapeutic Radiology at Yale School of Medicine in New Haven, CT. Henry S. Park, M.D., M.P.H., is at the Department of Therapeutic Radiology and at the Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale School of Medicine in New Haven, CT. James B. Yu, M.D., M.H.S., is at the Department of Therapeutic Radiology and at the Cancer Outcomes, Public Policy, and Effectiveness Research Center at Yale School of Medicine in New Haven, CT.

Firearm injuries are a significant public health problem. Prior studies have analyzed firearm death data or adult firearm injury data, but few studies have analyzed firearm injury data specifically among youth. To inform the current debate surrounding gun policy in the United States, this study aims to provide an estimate of the immense burden of youth firearm injury and its associated risk factors. Therefore, we performed a descriptive analysis of the Nationwide Emergency Department Sample (NEDS), the largest all-payer emergency department database in the United States, from January 2006 to September 2015. All patients age < 21 who presented with any diagnosis of firearm-related injuries were included.There were an estimated 198,839 incidents of firearm-related emergency department visits for patients age < 21 from 2006 through 2015. After presenting to the ED, an estimated 11,909 cases resulted in death. The population adjusted rate of firearm-related emergency department visits was highest in the South and Midwest. This study demonstrates the significant burden of firearm injury among youth. Having a reliable estimate of the number of children harmed by firearms each year is a critical tool for policymakers - and may make common-sense gun safety measures more politically possible.
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http://dx.doi.org/10.1177/1073110520979403DOI Listing
December 2020

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis.

Clin Transl Radiat Oncol 2021 Mar 16;27:15-23. Epub 2020 Dec 16.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

Purpose: Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown.

Methods: Patients with non-metastatic PDAC from 2006 to 2016 who received pre-operative MAC or MAC + RT before oncologic resection were identified in the National Cancer Database. Univariable and multivariable (MVA) associates with R0 resection were identified with logistic regression, and survival was analyzed secondarily with the Kaplan Meier method and Cox regression analysis.

Results: 4,599 patients were identified (MAC: 3,109, MAC + RT: 1,490). Compared to those receiving MAC, patients receiving MAC + RT were more likely to have cT3-4 disease (76% vs 64%, p < 0.001) and cN + disease (33% vs 29%, p = 0.010), but were less likely to have ypT3-4 disease (59% vs 74%, p < 0.001) and ypN + disease (32% vs 55%, p < 0.001) and more likely to have a pathologic complete response (5% vs 2%, p < 0.001) and R0 resection (86% vs 80%, p < 0.001). On MVA, MAC + RT (OR 1.58, 95% CI 1.33-1.89, p < 0.001), evaluation at an academic center (OR 1.33, 95% CI 1.14-1.56, p < 0.001), and female sex (OR 1.43, 95% CI 1.23-1.67, p < 0.001) were associated with higher odds of R0 resection, while cT3-4 disease (OR 0.81, 95% CI 0.68-0.96, p = 0.013) was associated with lower odds of R0 resection.

Conclusion: For patients with localized PDAC who receive pre-operative MAC, the addition of pre-operative RT was associated with improved rates of R0 resection and pathologic response.
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http://dx.doi.org/10.1016/j.ctro.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772693PMC
March 2021

Radiation Dose to the Rectum With Definitive Radiation Therapy and Hydrogel Spacer Versus Postprostatectomy Radiation Therapy.

Adv Radiat Oncol 2020 Nov-Dec;5(6):1225-1231. Epub 2020 Sep 15.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.

Purpose: Management options for localized prostate cancer include definitive radiation therapy (RT) or radical prostatectomy, with a subset of surgical patients requiring adjuvant or salvage RT after prostatectomy. The use of a peri-rectal hydrogel spacer in patients receiving definitive RT has been shown to reduce rectal doses and toxicity. However, in the postprostatectomy setting, a hydrogel spacer cannot be routinely placed. Therefore, we sought to compare rectal dosimetry between definitive RT with a hydrogel spacer versus postoperative RT.

Methods And Materials: We identified patients with prostate cancer who underwent conventionally fractionated RT. Rectal dosimetry was evaluated between 2 groups: definitive RT with a hydrogel spacer (79.2 Gy, group 1) and postoperative RT (70.2 Gy, group 2). Rectal dosimetry values were tabulated and compared using Mann-Whitney test. We implemented a Bonferroni correction to account for multiple comparisons (threshold < .005). Linear regression analysis evaluated predictors of candidate rectal dose-volume parameters.

Results: We identified 51 patients treated during years 2017 to 2018; 16 (31%) and 35 (69%) patients were included in groups 1 and 2, respectively. The rectal volume receiving ≥65 Gy (V65) was significantly lower in group 1 (median, 2.1%; interquartile range, 0.9%-3.1%) than in group 2 (10.7%, 6.6%-14.5%) ( < .001). Use of a hydrogel spacer in the definitive setting was independently associated with lower V65 ( < .001). Similar results were found for V60, V55, V50, and V45 ( < .005 for all).

Conclusions: Rectal dosimetry is more favorable for definitive RT (79.2 Gy) with a hydrogel spacer compared with postoperative RT (70.2 or 66.6 Gy). This may inform shared decision-making regarding primary management of prostate cancer, especially among patients at high risk of needing postoperative RT after prostatectomy.
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http://dx.doi.org/10.1016/j.adro.2020.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718530PMC
September 2020

Revisiting the Radiation Therapy Oncology Group 1221 Hypothesis: Treatment for Stage III/IV HPV-Negative Oropharyngeal Cancer.

Otolaryngol Head Neck Surg 2020 Nov 17:194599820969613. Epub 2020 Nov 17.

Division of Otolaryngology, Department of Surgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Objective: In 2014, the Radiation Therapy Oncology Group 1221 trial was initiated to analyze whether surgery with risk-based radiation therapy or chemoradiation therapy was superior to chemoradiation therapy alone in patients with clinically staged T1-2N1-2bM0 HPV-negative oropharyngeal squamous cell carcinoma. However, the study was prematurely terminated. Given the lack of a randomized controlled trial, we retrospectively approached the same question using large national cancer databases.

Study Design: Retrospective cohort study.

Setting: The National Cancer Database and Surveillance, Epidemiology, and End Results (SEER) program from 2010 to 2016.

Methods: We identified 3004 patients in the National Cancer Database and 670 patients in the SEER database. Statistical techniques included Kaplan-Meier survival analysis, binary and multinomial logistic regressions, Cox proportional hazard regressions, and inverse propensity score weighting.

Results: On weighted multivariable Cox regression, patients recommended to receive frontline surgery had improved overall survival as compared with those recommended to receive chemoradiation therapy alone (hazard ratio [HR], 0.77; 95% CI, 0.68-0.86). On post hoc multivariable analysis based on therapy actually received, frontline surgery with adjuvant chemoradiation therapy was associated with improved overall survival (HR, 0.59; 95% CI, 0.50-0.71) as compared with chemoradiation therapy without surgery. Analysis of the SEER cohort revealed improved overall survival (HR, 0.69; 95% CI, 0.54-0.87) and head and neck cancer-specific survival (HR, 0.59; 95% CI, 0.41-0.84) in patients recommended to receive frontline surgery over chemoradiation therapy alone.

Conclusion: Our findings support the use of surgery with risk-based addition of adjuvant therapy in patients with cT1-2N1-2bM0 HPV-negative oropharyngeal cancer.
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http://dx.doi.org/10.1177/0194599820969613DOI Listing
November 2020

Comparative efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of randomized trials.

Cancer 2021 Mar 29;127(5):709-719. Epub 2020 Oct 29.

Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut.

Background: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI.

Methods: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed.

Results: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs.

Conclusions: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.
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http://dx.doi.org/10.1002/cncr.33269DOI Listing
March 2021

Primary Treatment Selection for Clinically Node-Negative Merkel Cell Carcinoma of the Head and Neck.

Otolaryngol Head Neck Surg 2020 Oct 20:194599820967001. Epub 2020 Oct 20.

Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.

Objective: Merkel cell carcinoma practice guidelines recommend sentinel lymph node biopsy after wide local excision for the initial management of clinically node-negative disease without distant metastases (cN0M0). Despite guideline publication, treatment selection remains variable. We hypothesized that receipt of guideline-recommended care would be more common in patients evaluated at academic centers and institutions with high melanoma case volumes and that such therapy would be associated with improved overall survival.

Study Design: Retrospective cohort analysis.

Setting: The National Cancer Database from 2004 to 2015.

Methods: A total of 3500 patients were included. We utilized Kaplan-Meier analysis and logistic and Cox proportional hazard regressions. Survival analysis was performed on inverse probability-weighted cohorts.

Results: There has been a trend toward evaluation at academic programs at a rate of 1.58% of patients per year (95% CI, 1.06%-2.11%) since 2004. However, the percentage of patients receiving guideline-compliant primary tumor excision and lymph node evaluation has plateaued at approximately 50% since 2012. Guideline-compliant surgical management was more commonly provided to patients evaluated at academic programs than nonacademic programs but only when those institutions had a high melanoma case volume (odds ratio, 2.01; 95% CI, 1.62-2.48). Receipt of guideline-compliant primary tumor excision and lymph node evaluation was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.64-0.76).

Conclusion: Facility factors affect rates of receipt of guideline-compliant initial surgical management for patients with node-negative Merkel cell carcinoma. Given the survival benefit of such treatment, patients may benefit from care at hospitals with high melanoma case volumes.
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http://dx.doi.org/10.1177/0194599820967001DOI Listing
October 2020

Quantifying treatment selection bias effect on survival in comparative effectiveness research: findings from low-risk prostate cancer patients.

Prostate Cancer Prostatic Dis 2020 Sep 28. Epub 2020 Sep 28.

Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Background: Comparative effectiveness research (CER) using national registries influences cancer clinical trial design, treatment guidelines, and patient management. However, the extent to which treatment selection bias (TSB) affects overall survival (OS) in cancer CER remains poorly defined. We sought to quantify the TSB effect on OS in the setting of low-risk prostate cancer, where 10-year prostate cancer-specific survival (PCSS) approaches 100% regardless of treatment modality.

Methods: The Surveillance, Epidemiology, and End Results database was queried for patients with low-risk prostate cancer (cT1-T2a, PSA < 10, and Gleason 6) who received radical prostatectomy (RP), brachytherapy (BT), or external beam radiotherapy (EBRT) from 2005 to 2015. The TSB effect was defined as the unadjusted 10-year OS difference between modalities that was not due to differences in PCSS. Propensity score matching was used to estimate the TSB effect on OS due to measured confounders (variables present in the database and associated with OS) and unmeasured confounders.

Results: A total of 50,804 patients were included (8845 RP; 18,252 BT; 23,707 EBRT) with a median follow-up of 7.4 years. The 10-year PCSS for the entire cohort was 99%. The 10-year OS was 92.9% for RP, 83.6% for BT, and 76.9% for EBRT (p < 0.001). OS differences persisted after propensity score matching of RP vs. EBRT (7.4%), RP vs. BT (4.6%), and BT vs. EBRT (3.7%) (all p < 0.001). The TSB effect on 10-year OS was estimated to be 15.0% for RP vs. EBRT (8.6% measured, 6.4% unmeasured), 8.5% for RP vs. BT (4.8% measured, 3.7% unmeasured), and 6.5% for BT vs. EBRT (3.1% measured, 3.4% unmeasured).

Conclusions: Patients with low-risk prostate cancer selected for RP exhibited large OS differences despite similar PCSS compared to radiotherapy, suggesting OS differences are almost entirely driven by TSB. The quantities of these effects are important to consider when interpreting prostate cancer CER using national registries.
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http://dx.doi.org/10.1038/s41391-020-00291-3DOI Listing
September 2020

National Patterns in Prescription Opioid Use and Misuse Among Cancer Survivors in the United States.

JAMA Netw Open 2020 08 3;3(8):e2013605. Epub 2020 Aug 3.

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.

Importance: Prescription opioids are frequently prescribed to treat cancer-related pain. However, limited information exists regarding rates of prescription opioid use and misuse in populations with cancer.

Objectives: To estimate the prevalence and likelihood of prescription opioid use and misuse in adult cancer survivors compared with respondents without cancer and to identify characteristics associated with prescription opioid use and misuse in adult cancer survivors.

Design, Setting, And Participants: This cross-sectional study is a retrospective, population-based study using data from 169 162 respondents to the National Survey on Drug Use and Health from January 2015 to December 2018. Survey data sets were queried for all respondents aged 18 years or older. Those with a reported history of cancer were termed cancer survivors and further divided into more recent (had cancer within 12 months of survey) and less recent (had cancer more than 12 months prior to survey) cohorts. Respondents with nonmelanoma skin cancer were excluded.

Main Outcomes And Measures: Prescription opioid use and misuse within the past 12 months.

Results: Among 169 162 respondents, 5139 (5.2%) were cancer survivors, with 1243 (1.2%) and 3896 (4.0%) reporting having more recent and less recent cancer histories, respectively. Higher rates of prescription opioid use were observed among more recent cancer survivors (54.3%; 95% CI, 50.2%-58.4%; odds ratio [OR], 1.86; 95% CI, 1.57-2.20; P < .001) and less recent cancer survivors (39.2%; 95% CI, 37.3%-41.2%; OR, 1.18; 95% CI, 1.08-1.28; P < .001) compared with respondents without cancer (30.5%, reference group). Rates of prescription opioid misuse were similar among more recent (3.5%; 95% CI, 2.4%-5.2%; OR, 1.27; 95% CI, 0.82-1.96; P = .36) and less recent (3.0%; 95% CI, 2.4%-3.6%; OR, 1.03; 95% CI, 0.83-1.28; P = .76) survivors compared with respondents without cancer (4.3%, reference group). Younger age (aged 18-34 years vs ≥65 years: OR, 7.06; 95% CI, 3.03-16.41; P < .001), alcohol use disorder (OR, 3.22; 95% CI, 1.45-7.14; P = .005), and nonopioid drug use disorder (OR, 14.76; 95% CI, 7.40-29.44; P < .001) were associated with prescription opioid misuse among cancer survivors.

Conclusions And Relevance: In this study, prescription opioid use was higher among more and less recent cancer survivors compared with the population without a history of cancer. Rates of prescription opioid misuse were low and similar among all 3 cohorts. These findings suggest that higher prescription opioid use among cancer survivors may not correspond to increased short-term or long-term misuse.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.13605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431994PMC
August 2020

Multi-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy.

J Radiosurg SBRT 2020 ;7(1):19-27

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06511, USA.

Patients with small cell lung cancer (SCLC) brain metastasis (BM) typically receive whole brain radiotherapy (WBRT) as data regarding upfront radiosurgery (SRS) in this setting are sparse. Patients receiving SRS for SCLC BM without prior brain radiation were identified at three U.S. institutions. Overall survival (OS), freedom from intracranial progression (FFIP), freedom from WBRT (FFWBRT), and freedom from neurologic death (FFND) were determined from time of SRS. Thirty-three patients were included with a median of 2 BM (IQR 1-6). Median OS and FFIP were 6.7 and 5.8 months, respectively. Median FFIP for patients with ≤2 versus >2 BM was 7.1 versus 3.6 months, p=0.0303. Eight patients received salvage WBRT and the 6-month FFWBRT and FFND were 87.8%. and 90.1%, respectively. Most SCLC patients with BM who received upfront SRS avoided WBRT and neurologic death, suggesting that SRS may be an option in select patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406345PMC
January 2020

Temporal Trends in Opioid Prescribing Patterns Among Oncologists in the Medicare Population.

J Natl Cancer Inst 2021 Mar;113(3):274-281

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.

Background: In the wake of the US opioid epidemic, there have been efforts to curb opioid prescribing. However, it is unknown whether these efforts have affected prescribing among oncologists, whose patients often require opioids for symptom management. We investigated temporal patterns in opioid prescribing for Medicare beneficiaries among oncologists and nononcologists.

Methods: We queried the Centers for Medicare and Medicaid Services Part D prescriber dataset for all physicians between January 1, 2013, and December 31, 2017. We used population-averaged multivariable negative binomial regression to estimate the association between time and per-provider opioid and gabapentinoid prescribing rate, defined as the annual number of drug claims (original prescriptions and refills) per beneficiary, among oncologists and nononcologists on a national and state level.

Results: From 2013 to 2017, the national opioid-prescribing rate declined by 20.7% (P < .001) among oncologists and 22.8% (P < .001) among non oncologists. During this time frame, prescribing of gabapentin increased by 5.9% (P < .001) and 23.1% (P < .001) among oncologists and nononcologists, respectively. Among palliative care providers, opioid prescribe increased by 15.3% (P < .001). During the 5-year period, 43 states experienced a decrease (P < .05) in opioid prescribing among oncologists, and in 5 states, opioid prescribing decreased more among oncologists than nononcologists (P < .05).

Conclusions: Between 2013 and 2017, the opioid-prescribing rate statistically significantly decreased nationwide among oncologists and nononcologists, respectively. Given similar declines in opioid prescribing among oncologists and nononcologists, there is concern that opioid-prescribing guidelines intended for the noncancer population are being applied inappropriately to patients with cancer and cancer survivors.
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http://dx.doi.org/10.1093/jnci/djaa110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936059PMC
March 2021

Nationwide Patterns of Pathologic Fractures Among Patients Hospitalized With Bone Metastases.

Am J Clin Oncol 2020 10;43(10):720-726

Department of Therapeutic Radiology, Yale University School of Medicine.

Objectives: Pathologic fractures from bone metastases can significantly affect quality-of-life, although it is unclear which patients may be at high risk of this outcome. We aim to determine risk factors for pathologic fracture among patients admitted with bone metastases and to evaluate the association of pathologic fracture with clinical and economic outcomes.

Methods: The Healthcare Cost and Utilization Project National Inpatient Sample was queried for all patients hospitalized with bone metastases in 2016. Baseline differences between patients with and without pathologic fractures were assessed by χ and analysis of variance testing. Multivariable logistic regression was used to identify factors associated with fractures.

Results: In 2016, 272,275 hospital admissions were associated with a diagnosis of bone metastases, of which 11,960 (4.4%) had a primary diagnosis of pathologic fracture. Patients with pathologic fractures had a longer length-of-hospital-stay (mean 7.5 vs. 6.4 d; P<0.001) and higher cost-of-hospital-stay (mean $23,611 vs. $15,942; P<0.001) compared to patients without pathologic fractures. Primary cancers associated with increased likelihood of pathologic fracture included liver and intrahepatic bile duct (odds ratio [OR] 2.34; 95% confidence interval [CI], 1.65-3.32), multiple myeloma (OR 1.94; 95% CI, 1.31-2.86), and kidney and renal pelvis cancer (OR 1.89; 95% CI, 1.50-2.37).

Conclusions: Nearly 5% of hospitalizations with bone metastases presented with a concomitant pathologic fracture, which was associated with longer inpatient stay and higher cost. Patients with hepatobiliary, renal cell carcinoma, or multiple myeloma, had a higher likelihood of pathologic fracture. These groups may benefit from increased outpatient monitoring, prophylactic stabilization, or early irradiation.
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http://dx.doi.org/10.1097/COC.0000000000000737DOI Listing
October 2020

Resident attitudes and benefits of mock oral board examinations in radiation oncology.

BMC Med Educ 2020 Jun 26;20(1):203. Epub 2020 Jun 26.

Department of Therapeutic Radiology, Yale School of Medicine, 35 Park Street, New Haven, CT 06516, USA.

Background: Presently, educational programming is not standardized across radiation oncology (RO) training programs. Specifically, there are limited materials through national organizations or structured practice exams for residents preparing for the American Board of Radiology (ABR) oral board examination. We present our 2019 experience implementing a formalized program of early mock oral board examinations (MOBE) for residents in post-graduate years (PGY) 3-5.

Methods: A mixed-methods survey regarding MOBE perception and self-reported comfort across five clinical domains were administered to PGY2-5 residents. MOBEs and a post-intervention survey were implemented for the PGY3-5. The pre and post-intervention score across clinical domains were compared using t-tests. Faculty and residents were asked for post-intervention comments.

Results: A total of 14 PGY2-5 residents completed the pre-intervention survey; 9 residents participated in the MOBE (5/14 residents were PGY2s) and post-intervention survey. This was the first mock oral radiation oncology examination experience for 65% of residents. 100% of residents felt the MOBE increased their clinical knowledge and comfort with clinical reasoning. Overall, there was a trend towards improved resident confidence giving planning dose parameters and (p = 0.08). There was also unanimous request for more MOBE experiences from residents and faculty, but time was identified as a significant barrier.

Conclusions: Future directions for this MOBE program are inclusion of more disease sites, better emulation of the exam, the creation of a more rigorous consolidated format testing all sites at once, and consideration for grading of these sessions for future correlation with certifying oral board examination (OBE) performance.
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http://dx.doi.org/10.1186/s12909-020-02106-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318518PMC
June 2020

Nationwide patterns of hemorrhagic stroke among patients hospitalized with brain metastases: influence of primary cancer diagnosis and anticoagulation.

Sci Rep 2020 06 22;10(1):10084. Epub 2020 Jun 22.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA.

Brain metastases can contribute to a decreased quality of life for patients with cancer, often leading to malaise, neurologic dysfunction, or death. Intracerebral hemorrhage (ICH) is an especially feared complication in patients with brain metastases given the potential for significant morbidity and mortality. We aim to characterize patients with cancer and brain metastases admitted to hospitals nationwide and identify factors associated with ICH. The 2016 Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) was queried for all patients with cancer hospitalized with a diagnosis of brain metastases. Admissions with a primary or secondary diagnosis of ICH were further identified. Baseline differences in demographic, clinical, socioeconomic, and hospital-related characteristics between patients with and without ICH were assessed by chi-square, Mann-Whitney U, and ANOVA testing. Multivariable logistic regression was used to identify factors associated with ICH. Weighted frequencies were used to create national estimates for all data analysis. In 2016, a total 145,225 hospitalizations were associated with brain metastases, of which 4,145 (2.85%) had a concurrent diagnosis of ICH. Patients with ICH were more likely to have a longer length of stay (median 5 days vs 4 days, p < 0.001) and a higher cost of stay (median $14,241.14 vs $10,472.54, p  < 0.001). ICH was found to be positively associated with having a diagnosis of melanoma (odds ratio [OR] 5.01; 95% Confidence Interval [CI] 3.50-7.61) and kidney cancer (OR 2.50; 95% CI 1.69-3.72). Patients on long-term anticoagulation had a higher risk of ICH (OR 1.49; CI 1.15-1.91). Approximately 3% of patients hospitalized with brain metastases also had a diagnosis of ICH, which was significantly associated with longer length of stay and cost. Patients with melanoma, kidney cancer, and on long-term anticoagulation had a higher risk of ICH. Physicians should consider the risks of anticoagulation carefully for patients with brain metastases, especially those with melanoma and kidney cancer.
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http://dx.doi.org/10.1038/s41598-020-67316-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308286PMC
June 2020

National trends in the management of patients with positive surgical margins at radical prostatectomy.

World J Urol 2020 Jun 19. Epub 2020 Jun 19.

Department of Urology, Yale School of Medicine, 789 Howard Avenue, FMP 300, New Haven, CT, 06520, USA.

Purpose: To evaluate practice patterns of planned post-operative radiation therapy (RT) among men with positive surgical margins (PSM) at radical prostatectomy.

Methods: We identified 43,806 men within the National Cancer Database with pathologic node-negative prostate cancer diagnosed in 2010 through 2014 with PSM. The primary endpoint was receipt of planned (RT) within a patient's initial course of treatment. We examined post-RP androgen deprivation therapy (ADT) with RT as a secondary endpoint. We evaluated patterns of post-operative management and characteristics associated with planned post-prostatectomy RT.

Results: Within 12 months of RP, 87.0% received no planned RT, 8.5% RT alone, 1.3% ADT alone, and 3.1% RT with ADT. In a multivariable logistic regression model, planned RT use was associated with clinical and pathologic characteristics as estimated by surgical Cancer of the Prostate Risk Assessment (CAPRA-S) category (intermediate versus low, OR = 2.87, 95% CI 2.19-3.75, P < 0.001; high versus low, OR = 10.23, 95% CI 7.79-13.43, P < 0.001), treatment at community versus academic centers (OR = 1.24, 95% CI 1.15-1.34, P < 0.001), shorter distance to a treatment facility (OR = 0.97 for each 10-mile, 95% CI 0.96-0.98, P < 0.001), and uninsured status (OR = 1.39, 95% CI 1.10-1.77, P = 0.005). The odds of receiving planned RT were lower in 2014 versus 2010 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001). There was no significant change in the use of ADT with RT. High versus low CAPRA-S category was associated with the use of ADT in addition to RT (OR = 5.13, 95% CI 1.57-16.80, P = 0.007).

Conclusion: The use of planned post-prostatectomy RT remained stable among patients with PSM and appears driven primarily by the presence of other adverse pathologic features.
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http://dx.doi.org/10.1007/s00345-020-03298-6DOI Listing
June 2020

Mentorship in Radiation Oncology: Role of Gender Diversity in Abstract Presenting and Senior Author Dyads on Subsequent High-Impact Publications.

Adv Radiat Oncol 2020 Mar-Apr;5(2):292-296. Epub 2019 Oct 31.

Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.

Purpose: To generate insights regarding the role of gender in research mentorship, we analyzed characteristics of abstracts selected for oral and poster discussion presentations at the American Society for Radiation Oncology annual meeting and subsequent high-impact publications.

Methods And Materials: Clinical radiation oncology abstracts selected for oral and poster discussion presentations at the American Society for Radiation Oncology annual meetings in 2014 and 2015 were reviewed. A multivariable logistic regression model evaluated factors associated with subsequent higher-impact publications among abstracts that led to manuscript publications. The primary independent variable was the presenting-senior (last) author gender dyad (divided into 4 groups based on gender of presenting and senior authors, respectively; eg, "MF" indicates male presenting and female senior). Dyads were classified as MF, FM, MM, or FF.

Results: Data were derived from 390 oral and 142 poster discussions. Presenting and senior author pairings were MM for 286 (53.8%), FF for 67 (12.6%), MF for 84 (15.8%), and FM for 94 (17.7%) abstracts. Overall, 403 abstracts led to subsequent publications, of which 52.1% (210) were in a higher-impact journal. Eventual publication in a higher-impact journal was significantly associated with senior author H-index (odds ratio [OR] 3.30 for H ≥ 41 vs < 17; group = .007), grant support for the study (OR 2.09 for funded vs not, = .0261), and with the presenting and senior author gender pairing (group = .0107). Specifically, FM pairings (OR 2.48; 95% confidence interval, 1.32-4.66) and MF pairings (OR 2.38; 95% confidence interval, 1.19-4.77) had higher odds of high-impact publication than MM pairings, whereas there was no significant difference in this outcome between FF and MM pairings.

Conclusions: Although unmeasured confounding remains possible, MF and FM dyads of presenting and senior authors were more likely than MM dyads to obtain journal publication in a higher-impact journal. Institutions and the profession should support the development and maintenance of respectful, collaborative cross-gender mentorship.
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http://dx.doi.org/10.1016/j.adro.2019.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136636PMC
October 2019

Local Ablative Therapies for Oligometastatic and Oligoprogressive Non-Small Cell Lung Cancer.

Cancer J 2020 Mar/Apr;26(2):129-136

From the Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT.

More than half of all patients with non-small cell lung cancer (NSCLC) have metastatic disease at the time of diagnosis. A subset of these patients has oligometastatic disease, which exists in an intermediary state between locoregional and disseminated metastatic disease. In addition, some metastatic patients on systemic therapy may have limited disease progression, or oligoprogression. Historically, treatment of metastatic NSCLC was palliative in nature, with little expectation of long-term survival. However, an accumulation of evidence over the past 3 decades now demonstrates that local ablative therapy to sites of limited metastases or progression can improve patient outcomes for this complex disease. This review examines the evidence behind local ablative therapy in oligometastatic and oligoprogressive NSCLC, with a focus on surgery, stereotactic radiotherapy, and radiofrequency ablation.
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http://dx.doi.org/10.1097/PPO.0000000000000433DOI Listing
April 2021

Adjuvant external beam radiotherapy for surgically resected, nonmetastatic anaplastic thyroid cancer.

Head Neck 2020 05 3;42(5):1031-1044. Epub 2020 Feb 3.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.

Background: EBRT in resected, nonmetastatic anaplastic thyroid cancer (ATC) remains undefined. We evaluated patterns/outcomes with EBRT and chemotherapy in this setting.

Methods: This retrospective analysis included patients identified from the National Cancer Database with nonmetastatic ATC from 2004 to 2014 who underwent non-palliative resection.

Results: Our analysis included 496 patients, including 375 who underwent adjuvant EBRT (among whom 198 received concurrent chemotherapy). The median age was 68 years. On MVA, EBRT was associated with sex (OR 0.5, 95% CI 0.3-0.8, P = .002) and income (OR 2.2, 95% CI 1.4-3.3, P < .001). EBRT was associated with longer OS on UVA (12.3 vs 9.1 months, P = .004) and MVA (HR 0.7 [CI 0.6-0.9], P = .004). Concurrent chemoradiation was associated with longer OS on UVA (14.0 vs 9.1 months, P = .003) and MVA (HR 0.6 [CI 0.5-0.8], P < .001).

Conclusion: Adjuvant EBRT is associated with longer OS in resected, nonmetastatic ATC, with additional improved survival with concurrent chemotherapy.
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http://dx.doi.org/10.1002/hed.26086DOI Listing
May 2020

Adjuvant external beam radiotherapy for surgically resected, nonmetastatic anaplastic thyroid cancer.

Head Neck 2020 05 3;42(5):1031-1044. Epub 2020 Feb 3.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.

Background: EBRT in resected, nonmetastatic anaplastic thyroid cancer (ATC) remains undefined. We evaluated patterns/outcomes with EBRT and chemotherapy in this setting.

Methods: This retrospective analysis included patients identified from the National Cancer Database with nonmetastatic ATC from 2004 to 2014 who underwent non-palliative resection.

Results: Our analysis included 496 patients, including 375 who underwent adjuvant EBRT (among whom 198 received concurrent chemotherapy). The median age was 68 years. On MVA, EBRT was associated with sex (OR 0.5, 95% CI 0.3-0.8, P = .002) and income (OR 2.2, 95% CI 1.4-3.3, P < .001). EBRT was associated with longer OS on UVA (12.3 vs 9.1 months, P = .004) and MVA (HR 0.7 [CI 0.6-0.9], P = .004). Concurrent chemoradiation was associated with longer OS on UVA (14.0 vs 9.1 months, P = .003) and MVA (HR 0.6 [CI 0.5-0.8], P < .001).

Conclusion: Adjuvant EBRT is associated with longer OS in resected, nonmetastatic ATC, with additional improved survival with concurrent chemotherapy.
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http://dx.doi.org/10.1002/hed.26086DOI Listing
May 2020

Proton-Based Chemoradiotherapy-What Level of Evidence Is Necessary to Justify Its Widespread Use?

JAMA Oncol 2020 02;6(2):246-247

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1001/jamaoncol.2019.4875DOI Listing
February 2020

Emergency Department Visits for Opioid Overdoses Among Patients With Cancer.

J Natl Cancer Inst 2020 09;112(9):938-943

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.

Background: Patients with cancer may be at risk of high opioid use due to physical and psychosocial factors, although little data exist to inform providers and policymakers. Our aim is to examine overdoses from opioids leading to emergency department (ED) visits among patients with cancer in the United States.

Methods: The Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was queried for all adult cancer-related patient visits with a primary diagnosis of opioid overdose between 2006 and 2015. Temporal trends and baseline differences between patients with and without opioid-related ED visits were evaluated. Multivariable logistic regression analysis was used to identify risk factors associated with opioid overdose. All statistical tests were two-sided.

Results: Between 2006 and 2015, there were a weighted total of 35 339 opioid-related ED visits among patients with cancer. During this time frame, the incidence of opioid-related ED visits for overdose increased twofold (P < .001). On multivariable regression (P < .001), comorbid diagnoses of chronic pain (odds ratio [OR] 4.51, 95% confidence interval [CI] = 4.13 to 4.93), substance use disorder (OR = 3.54, 95% CI = 3.28 to 3.82), and mood disorder (OR = 3.40, 95% CI = 3.16 to 3.65) were strongly associated with an opioid-related visit. Patients with head and neck cancer (OR = 2.04, 95% CI = 1.82 to 2.28) and multiple myeloma (OR = 1.73, 95% CI = 1.32 to 2.26) were also at risk for overdose.

Conclusions: Over the study period, the incidence of opioid-related ED visits in patients with cancer increased approximately twofold. Comorbid diagnoses and primary disease site may predict risk for opioid overdose.
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http://dx.doi.org/10.1093/jnci/djz233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492769PMC
September 2020

Multi-Institutional Validation of Deep Learning for Pretreatment Identification of Extranodal Extension in Head and Neck Squamous Cell Carcinoma.

J Clin Oncol 2020 04 9;38(12):1304-1311. Epub 2019 Dec 9.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT.

Purpose: Extranodal extension (ENE) is a well-established poor prognosticator and an indication for adjuvant treatment escalation in patients with head and neck squamous cell carcinoma (HNSCC). Identification of ENE on pretreatment imaging represents a diagnostic challenge that limits its clinical utility. We previously developed a deep learning algorithm that identifies ENE on pretreatment computed tomography (CT) imaging in patients with HNSCC. We sought to validate our algorithm performance for patients from a diverse set of institutions and compare its diagnostic ability to that of expert diagnosticians.

Methods: We obtained preoperative, contrast-enhanced CT scans and corresponding pathology results from two external data sets of patients with HNSCC: an external institution and The Cancer Genome Atlas (TCGA) HNSCC imaging data. Lymph nodes were segmented and annotated as ENE-positive or ENE-negative on the basis of pathologic confirmation. Deep learning algorithm performance was evaluated and compared directly to two board-certified neuroradiologists.

Results: A total of 200 lymph nodes were examined in the external validation data sets. For lymph nodes from the external institution, the algorithm achieved an area under the receiver operating characteristic curve (AUC) of 0.84 (83.1% accuracy), outperforming radiologists' AUCs of 0.70 and 0.71 ( = .02 and = .01). Similarly, for lymph nodes from the TCGA, the algorithm achieved an AUC of 0.90 (88.6% accuracy), outperforming radiologist AUCs of 0.60 and 0.82 ( < .0001 and = .16). Radiologist diagnostic accuracy improved when receiving deep learning assistance.

Conclusion: Deep learning successfully identified ENE on pretreatment imaging across multiple institutions, exceeding the diagnostic ability of radiologists with specialized head and neck experience. Our findings suggest that deep learning has utility in the identification of ENE in patients with HNSCC and has the potential to be integrated into clinical decision making.
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http://dx.doi.org/10.1200/JCO.19.02031DOI Listing
April 2020

Strengths and limitations of large databases in lung cancer radiation oncology research.

Transl Lung Cancer Res 2019 Sep;8(Suppl 2):S172-S183

Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.

There has been a substantial rise in the utilization of large databases in radiation oncology research. The advantages of these datasets include a large sample size and inclusion of a diverse population of patients in a real-world setting. Such observational studies hold promise in enhancing our understanding of questions for which evidence is conflicting or absent in lung cancer radiotherapy. However, it is critical that investigators understand the strengths and limitations of large databases in order to avoid the common pitfalls that beset observational analyses. This review begins by outlining the data variables available in major registries that are used most often in observational analyses. This is followed by a discussion of the type of radiotherapy-related questions that can be addressed using such datasets, accompanied by examples from the lung cancer literature. Finally, we describe some limitations of observational research and techniques to mitigate bias and confounding. We hope that clinicians and researchers find this review helpful for designing new research studies and interpreting published analyses in the literature.
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http://dx.doi.org/10.21037/tlcr.2019.05.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795574PMC
September 2019

Impact of contralateral lymph nodal involvement and extranodal extension on survival of surgically managed HPV-positive oropharyngeal cancer staged with the AJCC eighth edition.

Oral Oncol 2019 12 17;99:104447. Epub 2019 Oct 17.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, USA; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Electronic address:

Objectives: Contralateral lymph node (LN) involvement is a prognostic factor in clinical staging of oropharyngeal squamous cell carcinoma (OPSCC), while pathologic nodal staging in the AJCC 8th edition for human papillomavirus-mediated OPSCC (HPV + OPSCC) focuses exclusively on the number of involved LNs (pLN+). This study assessed if the presence of contralateral pLN+ adds prognostic importance to the number of pLN+.

Materials And Methods: The National Cancer Database was queried for pLN+ HPV + OPSCC treated with surgery with 10 or more LN dissected. Data were evaluated with Cox regression, propensity score matching (PSM), and Kaplan-Meier overall survival (OS) analysis.

Results: Of 3407 patients, 152 (4.5%) patients had contralateral pLN+. Subjects with contralateral pLN+ had higher pT/pN stage, more positive margins, extranodal extension (ENE), and lymphovascular invasion (LVI) (all p < 0.05). On univariate analysis, contralateral pLN+ trended toward worse OS (HR 1.58, 95% CI 0.98-2.55, p = 0.061). In the multivariable model (controlling for age, comorbidities, T-stage, N-stage, LN size, ENE, LVI, margin status and adjuvant therapy), LN laterality had no impact on OS (HR 0.87, 95% CI 0.52-1.45, p = 0.520). Further PSM analysis confirmed that contralateral pLN+ is not associated with OS in this population (HR 0.79, 95% CI 0.41-1.53, p = 0.494).

Conclusion: This study supports the AJCC 8th edition pathologic staging for HPV + OPSCC by observing that LN laterality is not associated with OS. ENE was associated with inferior OS and should be considered for future staging systems. Further study should be directed at the importance of nodal size in this population.
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http://dx.doi.org/10.1016/j.oraloncology.2019.104447DOI Listing
December 2019

Clinical Outcomes of Head and Neck Cancer Patients Who Undergo Resection, But Forgo Adjuvant Therapy.

Anticancer Res 2019 Sep;39(9):4885-4890

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, U.S.A.

Background/aim: This study aimed to evaluate the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) who underwent resection and refused the recommended adjuvant therapy.

Patients And Methods: Locoregional recurrence-free survival (LRRFS) and time to progression (TTP) were assessed in HNSCC patients treated with surgery who declined some or all adjuvant therapy (refusal group (RG)) compared to those who received the recommended adjuvant therapy (TG).

Results: With a median follow-up of 23 months, the 2-year LRRFS was significantly lower in the 17 patients from the RG compared to the 152 patients from the TG: 23.1% vs. 69%, HR=0.30, 95% confidence incidence (CI)=0.15-0.59; p<0.001. The mean TTP was 12 months in the RG and was not reached in the TG (p<0.001).

Conclusion: Patients with HNSCC who declined the recommended adjuvant therapy had a recurrence rate of 50% within a year.
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http://dx.doi.org/10.21873/anticanres.13674DOI Listing
September 2019