Publications by authors named "Charles R Thomas"

328 Publications

The acid test: Call for a paradigm shift in philanthropic priorities for academic medical centers.

J Natl Med Assoc 2021 Apr 24. Epub 2021 Apr 24.

Massey Cancer Center Virginia Commonwealth University, Richmond, VA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jnma.2021.03.006DOI Listing
April 2021

Radiation-Induced Toxicity in the Era of Stereotactic Body Radiation Therapy-Lessons From NRG-BR001.

Authors:
Charles R Thomas

JAMA Oncol 2021 Apr 22. Epub 2021 Apr 22.

Radiation Medicine, Oregon Health Sciences University, Portland.

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http://dx.doi.org/10.1001/jamaoncol.2021.0677DOI Listing
April 2021

Detecting the Dark Matter of Unpublished Clinical Cancer Studies: An Analysis of Phase 3 Randomized Controlled Trials.

Mayo Clin Proc 2021 02;96(2):420-426

The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Unpublished randomized controlled trial (RCT) frequency, correlates, and financial impact are not well understood. We sought to characterize the nonpublication of peer-reviewed manuscripts among interventional, therapeutic, multi-arm, phase 3 oncology RCTs. Trials were identified by searching ClinicalTrials.gov, while publications and abstracts were identified through PubMed and Google Scholar. Trial data were extracted from ClinicalTrials.gov and individual publications. Publication was defined as a peer-reviewed manuscript addressing the primary endpoint. Patient accrual cost was extrapolated from experimental data; investigators/sponsors were contacted to determine nonpublication reasons. Six hundred eighty-four completed RCTs met inclusion criteria, which accrued 434,610 patients from 1994 to 2015; 638 were published (93.3%) and 46 were unpublished (6.7%). Among the unpublished trials, the time difference from primary endpoint maturity to data abstraction was a median of 6 years (interquartile range, 4 to 8 years). On multiple binary logistic regression analysis, factors associated with unpublished trials included lack of cooperative group sponsorship (odds ratio, 5.91, 95% CI, 1.35 to 25.97; P=.019) and supportive care investigation (odds ratio, 2.90; 95% CI, 1.13 to 7.41; P=.027). The estimated inflation-adjusted average cost of patient accrual for all unpublished trials was $113,937,849 (range, $41,136,883 to $320,201,063). Direct contact with sponsors/investigators led to a 50.0% response rate (n=23 of 46); manuscript in preparation and/or in submission (n=10 of 23) was the most commonly cited reason for nonpublication. In conclusion, approximately 1 in 15 clinical oncology RCTs are unpublished and this has a profound impact on the research enterprise. The cooperative group infrastructure may serve as a blueprint to reduce nonpublication.
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http://dx.doi.org/10.1016/j.mayocp.2020.08.015DOI Listing
February 2021

Patterns of Care and Barriers to Utilization of Definitive Concurrent Chemoradiation Therapy for Stage III Non-Small Cell Lung Cancer in Russia.

J Cancer Educ 2021 Feb 2. Epub 2021 Feb 2.

Department of Radiation Medicine, Knight Cancer Institute, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, KPV4, Portland, OR, 97239, USA.

Background: Definitive concurrent chemoradiation (cCRT) is offered to only 3% of Russian patients with stage III NSCLC. To determine the patterns of care and barriers to cCRT utilization in Russia, we conducted a survey of practicing radiation oncologists (ROs).

Methods: Electronic IRB-approved survey containing 15 questions was distributed to Russian ROs. Fisher's exact test or Cochran-Armitage test of trend was used to assess the associations between clinical experience, practice type, and patterns of care.

Results: We analyzed 58 questionnaires completed by ROs-16 respondents from tertiary referral hospitals, and 42 from community or private centers. A total of 88% of respondents formulate treatment recommendations in multi-disciplinary tumor boards. For unresectable stage III NSCLC, the most common recommendation is sequential CRT (50%), followed by concurrent CRT (40%), with an observed higher utilization of cCRT in tertiary centers (9/16, 56% vs 14/42, 33%). Of the respondents, 31% do not offer cCRT to their pts. Among reasons for avoiding cCRT are (1) poor performance of pts (76%); (2) high toxicity of therapy (55%); (3) lack of consensus among tumor board members (33%); and (4) preference for sequential CRT (31%). Only 3% do not irradiate elective LNs. Eighty-six percent of respondents counsel their NSCLC pts regarding smoking cessation.

Conclusions: Despite level 1 evidence, cCRT is rarely used in Russia for pts with locally advanced NSCLC, and preference for sequential therapy and concerns over high toxicity are the most common barriers. Education of Russian ROs may increase cCRT utilization, leading to improved survival, notably in the era of maintenance immunotherapy.
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http://dx.doi.org/10.1007/s13187-021-01966-8DOI Listing
February 2021

Cancer pain management in the emergency department: a multicenter prospective observational trial of the Comprehensive Oncologic Emergencies Research Network (CONCERN).

Support Care Cancer 2021 Jan 22. Epub 2021 Jan 22.

Departments of Emergency Medicine and Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Purpose: Many patients with cancer seek care for pain in the emergency department (ED). Prospective research on cancer pain in this setting has historically been insufficient. We conducted this study to describe the reported pain among cancer patients presenting to the ED, how pain is managed, and how pain may be associated with clinical outcomes.

Methods: We conducted a multicenter cohort study on adult patients with active cancer presenting to 18 EDs in the USA. We reported pain scores, response to medication, and analgesic utilization. We estimated the associations between pain severity, medication utilization, and the following outcomes: 30-day mortality, 30-day hospital readmission, and ED disposition.

Results: The study population included 1075 participants. Those who received an opioid in the ED were more likely to be admitted to the hospital and were more likely to be readmitted within 30 days (OR 1.4 (95% CI: 1.11, 1.88) and OR 1.56 (95% CI: 1.17, 2.07)), respectively. Severe pain at ED presentation was associated with increased 30-day mortality (OR 2.30, 95% CI: 1.05, 5.02), though this risk was attenuated when adjusting for clinical factors (most notably functional status).

Conclusions: Patients with severe pain had a higher risk of mortality, which was attenuated when correcting for clinical characteristics. Those patients who required opioid analgesics in the ED were more likely to require admission and were more at risk of 30-day hospital readmission. Future efforts should focus on these at-risk groups, who may benefit from additional services including palliative care, hospice, or home-health services.
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http://dx.doi.org/10.1007/s00520-021-05987-3DOI Listing
January 2021

The Feasibility of Patient-Specific Circulating Tumor DNA Monitoring throughout Multi-Modality Therapy for Locally Advanced Esophageal and Rectal Cancer: A Potential Biomarker for Early Detection of Subclinical Disease.

Diagnostics (Basel) 2021 Jan 5;11(1). Epub 2021 Jan 5.

Department of Radiation Medicine, Oregon Health & Science University (OHSU), 3181 SW Sam Jackson Park Rd, KPV4, Portland, OR 97239, USA.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal ( = 3) and rectal cancer ( = 2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the Dual-Index Degenerate Adaptor-Sequencing (DIDA-Seq) error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient- and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.
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http://dx.doi.org/10.3390/diagnostics11010073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824834PMC
January 2021

Increasing Rate of Unintentional Firearm Deaths in Youngest Americans: Firearm Prevalence and Covid-19 Pandemic Implication.

J Natl Med Assoc 2021 Jan 11. Epub 2021 Jan 11.

Department of Radiation Medicine and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.

Background: The United States has had, by far, the world's greatest civilian ownership of firearms. An even greater ownership occurred during the Covd-19 pandemic, mostly of handguns and including many new owners. The U.S. has also had the least progress of the 41 highest sociodemographic countries ranked by the Institute for Health Metrics and Evaluation in reducing the unintentional firearm mortality rate in young children. This study characterized the unintentional firearm mortality trends in American 1-4 year-olds by sex and race/ethnicity and evaluated the trends in the context of firearm prevalence in the U.S.

Methods: Mortality data for 1999-2018 were obtained from the U.S. Centers for Disease Control and Prevention and the Institute for Health Metrics and Evaluation, firearm injury and mortality data for 2016-2020 from Everytown for Gun Safety #NotAnAccident database, firearm background check data for 1999-2020 from the National Instant Criminal Background Check System, and civilian firearm prevalence for 2017 from the Small Arms Survey.

Results: In American 1-4 year-olds, the rate of unintentional firearm deaths during 1999-2018 increased exponentially at an average annual percent rate of 4.9 (p < 0.001) and was greatest in non-Hispanic black children. Unintentional firearm deaths had the most rapid increase of all evaluable causes of death in the age group. The unintentional firearm death rate increase was correlated with the concurrent rate of firearm background checks and handgun permits issued (each p < 0.001) and in non-Hispanic white children with handgun prevalence in their families (p = 0.03). Globally, the unintentional firearm death rate was also correlated with firearm prevalence (p = 0.02).

Conclusions: An increase in fatal firearm accidents in the United States death rate among 1-4 year-olds is directly associated with the steadily increasing prevalence of firearms. The acceleration of firearm deaths and injuries among young Americans, especially among non-Hispanic black children, requires urgent solutions to address firearm prevalence and access. The problem is expected to become even more urgent as a result of the record high firearm sales that occurred in the United States during the 2020 coronavirus pandemic.
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http://dx.doi.org/10.1016/j.jnma.2020.12.005DOI Listing
January 2021

Mentorship Initiatives in Radiation Oncology: A Scoping Review of the Literature.

Int J Radiat Oncol Biol Phys 2021 Jun 4;110(2):292-302. Epub 2021 Jan 4.

Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois. Electronic address:

Purpose: Although mentorship is described extensively in academic medical literature, there are few descriptions of mentorship specific to radiation oncology. The goal of the current study was to investigate the state of mentorship in radiation oncology through a scoping review of the literature.

Methods And Materials: A search protocol was defined according to Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Predefined search terms and medical subject headings were used to search PubMed for English language articles published after January 1, 1990, on mentorship in radiation oncology. Additionally, in-press articles from major radiation oncology and medical education journals were searched. Three reviewers determined article eligibility. Included articles were classified based on predefined evaluation criteria.

Results: Fourteen publications from 2008 to 2019 met inclusion criteria. The most commonly described form of mentorship was the dyad (64.3%), followed by team (14.3%) and peer (7.1%); 2 articles did not specify mentorship type (14.3%). The most commonly mentored participants were residents (35.7%), followed by medical students (35.7%) and attendings (21.4%); 1 study included participants of all levels (7.1%). Thirteen studies (92.9%) identified an experimental study design, most of which were cross-sectional (42.9%), followed by cohort studies (28.6%) and before/after (21.4%). Median sample size, reported in 12 of 13 experimental studies, was 132 (coefficient of variation, 1.06). Although outcomes varied widely, the majority described successful implementation of mentorship initiatives with high levels of participant satisfaction.

Conclusions: Although few initiatives are currently reported, the present study suggests that these initiatives are successful in promoting career development and increasing professional satisfaction. The interventions overwhelmingly described mentorship dyads; other forms of mentorship are either less common or understudied. Limitations included interventions not being evaluated in a controlled setting, and many were assessed using surveys with low response rates. This review highlights rich opportunities for future scholarship to develop, evaluate, and disseminate radiation oncology mentorship initiatives.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.049DOI Listing
June 2021

Fucoidan-coated nanoparticles target radiation-induced P-selectin to enhance chemoradiotherapy in murine colorectal cancer.

Cancer Lett 2021 Mar 21;500:208-219. Epub 2020 Nov 21.

Department of Pharmaceutical Sciences, Oregon State University, 2730 S Moody Ave, Portland, OR, 97201, USA; Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. Electronic address:

Colorectal cancer (CRC) is a leading cause of cancer-related death for both men and women, highlighting the need for new treatment strategies. Advanced disease is often treated with a combination of radiation and cytotoxic agents, such as DNA damage repair inhibitors and DNA damaging agents. To optimize the therapeutic window of these multimodal therapies, advanced nanomaterials have been investigated to deliver sensitizing agents or enhance local radiation dose deposition. In this study, we demonstrate the feasibility of employing an inflammation targeting nanoscale metal-organic framework (nMOF) platform to enhance CRC treatment. This novel formulation incorporates a fucoidan surface coating to preferentially target P-selectin, which is over-expressed or translocated in irradiated tumors. Using this radiation stimulated delivery strategy, a combination PARP inhibitor (talazoparib) and chemotherapeutic (temozolomide) drug-loaded hafnium and 1,4-dicarboxybenzene (Hf-BDC) nMOF was evaluated both in vitro and in vivo. Significantly, these drug-loaded P-selectin targeted nMOFs (TT@Hf-BDC-Fuco) show improved tumoral accumulation over multiple controls and subsequently enhanced therapeutic effects. The integrated radiation and nanoformulation treatment demonstrated improved tumor control (reduced volume, density, and growth rate) and increased survival in a syngeneic CRC mouse model. Overall, the data from this study support the continued investigation of radiation-priming for targeted drug delivery and further consideration of nanomedicine strategies in the clinical management of advanced CRC.
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http://dx.doi.org/10.1016/j.canlet.2020.11.021DOI Listing
March 2021

Racial and Ethnic Disparities Among Participants in US-Based Phase 3 Randomized Cancer Clinical Trials.

JNCI Cancer Spectr 2020 Oct 7;4(5):pkaa060. Epub 2020 Jul 7.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Although improving representation of racial and ethnic groups in United States clinical trials has been a focus of federal initiatives for nearly 3 decades, the status of racial and ethnic minority enrollment on cancer trials is largely unknown. We used a broad collection of phase 3 cancer trials derived from ClinicalTrials.gov to evaluate racial and ethnic enrollment among US cancer trials. The difference in incidence by race and ethnicity was the median absolute difference between trial and corresponding Surveillance, Epidemiology, and End Results data. All statistical tests were 2-sided. Using a cohort of 168 eligible trials, median difference in incidence by race and ethnicity was +6.8% for Whites (interquartile range [IQR] = +1.8% to +10.1%; < .001 by Wilcoxon signed-rank test comparing median difference in incidence by race and ethnicity to a value of 0), -2.6% for Blacks (IQR = -5.1% to +1.2%; = .004), -4.7% for Hispanics (IQR = -7.5% to -0.3%; < .001), and -4.7% for Asians (IQR = -5.7% to -3.3%; < .001). These data demonstrate overrepresentation of Whites, with continued underrepresentation of racial and ethnic minority subgroups.
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http://dx.doi.org/10.1093/jncics/pkaa060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667997PMC
October 2020

Linguistic Biases in Letters of Recommendation for Radiation Oncology Residency Applicants from 2015 to 2019.

J Cancer Educ 2020 Oct 27. Epub 2020 Oct 27.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1140, Houston, TX, 77030, USA.

We aimed to investigate whether implicit linguistic biases exist in letters of recommendation (LORs) for applicants to radiation oncology (RO) residency. LORs (n = 487) written for applicants (n = 125) invited to interview at a single RO residency program from the 2015 to 2019 application cycles were included for analysis. Linguistic Inquiry and Word Count (LIWC) software was used to evaluate LORs for length and a dictionary of predetermined themes. Language was evaluated for gender bias using a publicly available gender bias calculator. Non-parametric tests were used to compare linguistic domain scores. The median number of the LORs per applicant was 4 (range 3-5). No significant differences by applicant gender were detected in LIWC score domains or gender bias calculator (P > 0.05). However, LORs for applicants from racial/ethnic backgrounds underrepresented in medicine were less likely to include standout descriptors (P = 0.008). Male writers were less likely to describe applicant characteristics related to patient care (P < 0.0001) and agentic personality (P = 0.006). LORs written by RO were shorter (P < 0.0001) and included fewer standout descriptors (P = 0.014) but were also more likely to include statements regarding applicant desirability (P = 0.045) and research (P = 0.008). While language was globally male-biased, assistant professors were less likely than associate professors (P = 0.0064) and full professors (P = 0.023) to use male-biased language. Significant linguistic differences were observed in RO residency LORs, suggesting that implicit biases related to both applicants and letter writers may exist. Recognition, and ideally eradication, of such biases are crucial for fair and equitable evaluation of a diverse applicant pool of RO residency candidates.
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http://dx.doi.org/10.1007/s13187-020-01907-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591242PMC
October 2020

Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

Pract Radiat Oncol 2021 Jan-Feb;11(1):13-25. Epub 2020 Oct 21.

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. Electronic address:

Purpose: This guideline reviews the evidence and provides recommendations for the indications and appropriate technique and dose of neoadjuvant radiation therapy (RT) in the treatment of localized rectal cancer.

Methods: The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the use of RT in preoperative management of operable rectal cancer. These questions included the indications for neoadjuvant RT, identification of appropriate neoadjuvant regimens, indications for consideration of a nonoperative or local excision approach after chemoradiation, and appropriate treatment volumes and techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: Neoadjuvant RT is recommended for patients with stage II-III rectal cancer, with either conventional fractionation with concurrent 5-FU or capecitabine or short-course RT. RT should be performed preoperatively rather than postoperatively. Omission of preoperative RT is conditionally recommended in selected patients with lower risk of locoregional recurrence. Addition of chemotherapy before or after chemoradiation or after short-course RT is conditionally recommended. Nonoperative management is conditionally recommended if a clinical complete response is achieved after neoadjuvant treatment in selected patients. Inclusion of the rectum and mesorectal, presacral, internal iliac, and obturator nodes in the clinical treatment volume is recommended. In addition, inclusion of external iliac nodes is conditionally recommended in patients with tumors invading an anterior organ or structure, and inclusion of inguinal and external iliac nodes is conditionally recommended in patients with tumors involving the anal canal.

Conclusions: Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for rectal cancer. Future studies will look to further personalize treatment recommendations to optimize treatment outcomes and quality of life.
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http://dx.doi.org/10.1016/j.prro.2020.08.004DOI Listing
October 2020

Performance Status Restriction in Phase III Cancer Clinical Trials.

J Natl Compr Canc Netw 2020 10 1;18(10):1322-1326. Epub 2020 Oct 1.

The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS.

Methods: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time.

Results: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS.

Conclusions: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.
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http://dx.doi.org/10.6004/jnccn.2020.7578DOI Listing
October 2020

Trial Sponsorship and Time to Reporting for Phase 3 Randomized Cancer Clinical Trials.

Cancers (Basel) 2020 Sep 16;12(9). Epub 2020 Sep 16.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

The pace of clinical trial data generation and publication is an area of interest within clinical oncology; however, little is known about the dynamics and covariates of time to reporting (TTR) of trial results. To assess these, ClinicalTrials.gov was queried for phase three clinical trials for patients with metastatic solid tumors, and the factors associated with TTR from enrollment completion to publication were analyzed. Based on the 319 included trials, cooperative-group-sponsored trials were reported at a slower rate than non-cooperative-group trials (median 37.5 vs. 31.0 months; < 0.001), while industry-funded studies were reported at a faster rate than non-industry-supported trials (31.0 vs. 40.0 months; = 0.005). Furthermore, successful trials (those meeting their primary endpoint) were reported at a faster rate than unsuccessful studies (27.5 vs. 36.0 months; < 0.001). Multivariable analysis confirmed that industry funding was independently associated with a shorter TTR ( = 0.006), while cooperative group sponsorship was not associated with a statistically significant difference in TTR ( = 0.18). These data underscore an opportunity to improve cooperative group trial efficiency by reducing TTR.
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http://dx.doi.org/10.3390/cancers12092636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563891PMC
September 2020

Increasing Medical Student Engagement Through Virtual Rotations in Radiation Oncology.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100538. Epub 2020 Aug 29.

Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon.

Corona virus disease 2019 (COVID-19) affected medical student clerkships and education around the country. A virtual medical student clerkship was created to integrate didactic education with disease specific lectures for medical students, contouring, and hands on learning with telehealth. Twelve medical students in their 3rd and 4th year were enrolled in this 2 week elective from April 27, 2020 to June 5, 2020. There was significant improvement of overall knowledge about the field of radiation oncology from pre elective to post elective (P < .001). Feedback included enjoying direct exposure to contouring, telehealth, and time with residents. Overall this 2 week rotation was successful in integrating radiation oncology virtually for medical students. This is now being expanded to multiple institutions as an educational resource and future rotations for medical students.
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http://dx.doi.org/10.1016/j.adro.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456273PMC
August 2020

Progression-free survival is a suboptimal predictor for overall survival among metastatic solid tumour clinical trials.

Eur J Cancer 2020 09 20;136:176-185. Epub 2020 Jul 20.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:

Background: The use of overall survival (OS) as the gold standard primary end-point (PEP) in metastatic oncologic randomised controlled trials (RCTs) has declined in favour of progression-free survival (PFS) without a complete understanding of the degree to which PFS reliably predicts for OS.

Methods: Using ClinicalTrials.gov, we identified 1239 phase III oncologic RCTs, 260 of which were metastatic solid tumour trials with a superiority-design investigating a therapeutic intervention by using either a PFS or OS PEP. Each individual trial was reviewed to quantify RCT design factors and disease-related outcomes.

Results: A total of 172,133 patients were enrolled from the year 1999 to 2015 in RCTs that used PFS (56.2%, 146/260) or OS (43.8%, 114/260) as the PEP. PFS trials were more likely to restrict patient eligibility by using molecular criteria (15.1% versus 4.4%, p = 0.005) use targeted therapy (80.1% versus 67.5%, p = 0.048), accrue fewer patients (median 495 versus 619, p = 0.03), and successfully meet the trial PEP (66.9% versus 33.3%, p < 0.0001). On multiple binary logistic regression analysis, factors that predicted for PFS or OS PEP trial success included choice of PFS PEP (p < 0.0001), molecular profile restriction (p = 0.02) and single agent therapy (p = 0.02). Notably, there was only a 38% (31/82) conversion rate of positive PFS-to-OS benefit; lack of industry sponsorship predicted for PFS-to-OS signal conversion (80.0% without industry sponsorship versus 35.1% with industry sponsorship, p = 0.045).

Conclusions: A PFS PEP has suboptimal positive predictive value for OS among phase III metastatic solid tumour RCTs. Regulatory agency decisions should be judicious in using PFS results as the primary basis for approval.
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http://dx.doi.org/10.1016/j.ejca.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702022PMC
September 2020

Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma.

CA Cancer J Clin 2020 09 19;70(5):375-403. Epub 2020 Jul 19.

Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon.

Despite tremendous gains in the molecular understanding of exocrine pancreatic cancer, the prognosis for this disease remains very poor, largely because of delayed disease detection and limited effectiveness of systemic therapies. Both incidence rates and mortality rates for pancreatic cancer have increased during the past decade, in contrast to most other solid tumor types. Recent improvements in multimodality care have substantially improved overall survival, local control, and metastasis-free survival for patients who have localized tumors that are amenable to surgical resection. The widening gap in prognosis between patients with resectable and unresectable or metastatic disease reinforces the importance of detecting pancreatic cancer sooner to improve outcomes. Furthermore, the developing use of therapies that target tumor-specific molecular vulnerabilities may offer improved disease control for patients with advanced disease. Finally, the substantial morbidity associated with pancreatic cancer, including wasting, fatigue, and pain, remains an under-addressed component of this disease, which powerfully affects quality of life and limits tolerance to aggressive therapies. In this article, the authors review the current multidisciplinary standards of care in pancreatic cancer with a focus on emerging concepts in pancreatic cancer detection, precision therapy, and survivorship.
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http://dx.doi.org/10.3322/caac.21626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722002PMC
September 2020

I Can't Breathe: The Continued Disproportionate Exclusion of Black Physicians in the United States Radiation Oncology Workforce.

Int J Radiat Oncol Biol Phys 2020 11 12;108(4):856-863. Epub 2020 Jul 12.

Department of Radiation Oncology, Stanford University, Stanford, California.

Purpose: Black physicians remain disproportionately underrepresented in certain medical specialties, yet comprehensive assessments in radiation oncology (RO) are lacking. Our purpose was to report current and historical representation trends for Black physicians in the US RO workforce.

Methods And Materials: Public registries were used to assess significant differences in 2016 representation for US vs RO Black academic full-time faculty, residents, and applicants. Historical changes from 1970 to 2016 were reported descriptively. Linear regression was used to assess significant changes for Black residents and faculty from 1995 to 2016.

Results: In 2016, Black people represented 3.2% vs 1.5% (P < .001), 5.6% vs 3.2% (P = .005), and 6.5% vs 5.4% (P = .352) of US vs RO faculty, residents, and applicants, respectively. Although RO residents nearly doubled from 374 (1974) to 720 (2016), Black residents peaked at 31 in 1984 (5.9%; 31 of 522) and fell to 23 (3.2%; 23 of 720) in 2016 across 91 accredited programs; Black US graduate medical education trainees nearly doubled over the same period: 3506 (1984) to 6905 (2016). From 1995 to 2016, Black US resident representation significantly increased by 0.03%/y, but decreased significantly in RO by -0.20%/y before 2006 and did not change significantly thereafter. Over the same period, Black US faculty representation significantly increased by 0.02%/y, whereas Black RO faculty significantly increased by 0.07%/y before 2006, then decreased significantly by -0.16%/y thereafter. The number of Black RO faculty peaked at 37 in 2006 (3.1%; 37 of 1203) and was 27 (1.5%; 27 of 1769) in 2016, despite the nearly 1.5-fold increase in the number of both RO faculty and Black US faculty overall (4169 in 2006 and 6047 in 2016) during that period.

Conclusions: Black physicians remain disproportionately underrepresented in RO despite an increasing available pipeline in the US physician workforce. Deliberate efforts to understand barriers to specialty training and inclusion, along with evidence-based targeted interventions to overcome them, are needed to ensure diversification of the RO physician workforce.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354371PMC
November 2020

Structural Solutions for the Rarest of the Rare - Underrepresented-Minority Faculty in Medical Subspecialties.

N Engl J Med 2020 07;383(3):283-285

From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington School of Medicine and Seattle Cancer Care Alliance, Seattle (K.M.D.); and the Department of Radiation Medicine, Oregon Health and Sciences University, Portland (C.R.T.).

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http://dx.doi.org/10.1056/NEJMms2003544DOI Listing
July 2020

What happens next: Radiation oncology after COVID?

Clin Transl Radiat Oncol 2020 Jul 30;23:89-90. Epub 2020 May 30.

Department of Radiation Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, KPV4, Portland, OR, 97239, United States.

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http://dx.doi.org/10.1016/j.ctro.2020.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261067PMC
July 2020

Longitudinal Health-related Quality of Life among Individuals Considering Treatment for Stage I Non-Small-Cell Lung Cancer.

Ann Am Thorac Soc 2020 08;17(8):988-997

Center to Improve Veteran Involvement in Care and.

Because of improvements in screening, there is an increasing number of patients with early-stage non-small-cell lung cancer (NSCLC) who are making treatment decisions. Among patients with suspected stage I NSCLC, we evaluated longitudinal patient-centered outcomes (PCOs) and the association of changes in PCOs with treatment modality, stereotactic body radiotherapy (SBRT) compared with surgical resection. We conducted a multisite, prospective, observational cohort study at seven medical institutions. We evaluated minimum clinically important differences of PCOs at four time points (during treatment, 4-6 wk after treatment, 6 mo after treatment, and 12 mo after treatment) compared with pretreatment values using validated instruments. We used adjusted linear mixed models to examine whether the association between treatment and European Organization for Research and Treatment of Cancer global and physical quality-of-life (QOL) scales differed over time. We included 127 individuals with stage I NSCLC (53 surgery, 74 SBRT). At 12 months, approximately 30% of patients remaining in each group demonstrated a clinical deterioration on global QOL from baseline. There was a significant difference in slopes between treatment groups on global QOL (-12.86; 95% confidence interval [CI], -13.34 to -12.37) and physical QOL (-28.71; 95% CI, -29.13 to -28.29) between baseline and during treatment, with the steeper decline observed among those who underwent surgery. Differences in slopes between treatment groups were not significant at all other time points. Approximately 30% of patients with stage I NSCLC have a clinically significant decrease in QOL 1 year after SBRT or surgical resection. Surgical resection was associated with steeper declines in QOL immediately after treatment compared with SBRT; however, these declines were not lasting and resolved within a year for most patients. Our results may facilitate treatment option discussions for patients receiving treatment for early-stage NSCLC.
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http://dx.doi.org/10.1513/AnnalsATS.202001-029OCDOI Listing
August 2020

What is our threshold: Departmental planning for radiation oncology's future in the time of COVID-19.

Radiother Oncol 2020 08 7;149:46-47. Epub 2020 May 7.

Department of Radiation Medicine, Oregon Health and Science University, Portland, United States. Electronic address:

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http://dx.doi.org/10.1016/j.radonc.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204682PMC
August 2020

"Was It Worth It?": A Pilot Study in Patient Perspectives on the Worthwhileness of Radiation Therapy.

Am J Clin Oncol 2020 08;43(8):598-601

Department of Radiation Medicine.

Objectives: Radiation therapy is a core oncologic treatment, but literature detailing patient satisfaction post-treatment is sparse. The authors conducted a pilot study to determine whether a simple survey would be feasible to administer and could elucidate factors predictive of satisfaction with radiotherapy.

Materials And Methods: Patients with cancer receiving radiotherapy in an academic radiation oncology department from 2014 to 2015 received a 4-item radiotherapy-focused version of the "Was It Worth It?" questionnaire (r-WIWI) on the last day of treatment and at the first follow-up. Univariate analysis and logistic regression modeling were performed on collected patient and treatment characteristics to explore predictors of satisfaction.

Results: Two hundred patients completed an r-WIWI questionnaire at treatment completion and 60 at the time of the first follow-up. Seventy-one percent and 90% of patients found radiotherapy worthwhile on the last day of treatment and at first follow-up, respectively. Patients treated during the morning and for a longer duration as measured in elapsed days were more likely to report treatment being worthwhile. Age, sex, race, marital status, employment status, treatment intent or modalities, daily radiation treatment delays, distance traveled, insurance type, site of treatment, and cancer stage were not predictive of patient satisfaction.

Conclusions: The r-WIWI survey was feasible to administer and most patients reported treatment being worthwhile on the last day of treatment and at first follow-up. Morning treatment times and longer treatment duration as measured in elapsed days were predictive of higher satisfaction in this pilot study. A broader study of factors associated with patient satisfaction with radiotherapy using the r-WIWI is indicated.
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http://dx.doi.org/10.1097/COC.0000000000000711DOI Listing
August 2020

Socioeconomic Factors Associated With Burnout Among Oncology Trainees.

JCO Oncol Pract 2020 04;16(4):e415-e424

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: Burnout in the medical workforce leads to early retirement, absenteeism, career changes, financial losses for medical institutions, and adverse outcomes for patients. Recent literature has explored burnout in different specialties of medicine. This article examines burnout among medical oncology trainees and identifies factors associated with burnout and professional dissatisfaction, including socioeconomic factors.

Methods: US medical oncology programs were sent a survey that included the Maslach Burnout Index-Human Services Survey as well as demographic, socioeconomic, and program-specific questions tailored to medical oncology fellowship. Primary binary end points included burnout, satisfaction with being a physician, and satisfaction with being a medical oncologist. Binomial logistic models determined associations between various characteristics and end points.

Results: Overall, 261 US fellows completed the survey. Seventy percent of international medical graduates reported no educational debt, whereas only 36% of US graduates reported no educational debt. Eighty-two percent of survey respondents reported their mother had at least a bachelor's degree, and 87% of respondents reported their father had at least a bachelor's degree. At least 27% of respondents had symptoms of burnout. Factors inversely associated with burnout on multivariable analysis included having a mother who graduated college (odds ratio [OR], 0.27), reporting an adequate perceived balance between work and personal life (OR, 0.22), feeling that faculty care about educational success (OR, 0.16), and being in the final year of training (OR, 0.45). Having debt ≥ $150,000 (OR, 2.14) was directly associated with burnout.

Conclusion: Symptoms of burnout are common among medical oncology fellows and are associated with educational debt and socioeconomic factors.
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http://dx.doi.org/10.1200/JOP.19.00703DOI Listing
April 2020

Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.

Clin Lung Cancer 2020 09 7;21(5):443-449.e4. Epub 2020 Mar 7.

Department of Radiation Medicine, Oregon Health & Science University, Portland, OR. Electronic address:

Background: Traditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC.

Materials And Methods: We surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses.

Results: We received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes.

Conclusion: Nearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.
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http://dx.doi.org/10.1016/j.cllc.2020.02.020DOI Listing
September 2020

Differential regulation of microRNA-15a by radiation affects angiogenesis and tumor growth via modulation of acid sphingomyelinase.

Sci Rep 2020 03 27;10(1):5581. Epub 2020 Mar 27.

Department of Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.

Activation of acid sphingomyelinase (SMPD1) and the generation of ceramide is a critical regulator of apoptosis in response to cellular stress including radiation. Endothelial SMPD1 has been shown to regulate tumor responses to radiation therapy. We show here that the SMPD1 gene is regulated by a microRNA (miR), miR-15a, in endothelial cells (ECs). Standard low dose radiation (2 Gy) upregulates miR-15a and decreases SMPD1 levels. In contrast, high dose radiation (10 Gy and above) decreases miR-15a and increases SMPD1. Ectopic expression of miR-15a decreases both mRNA and protein levels of SMPD1. Mimicking the effects of high dose radiation with a miR-15a inhibitor decreases cell proliferation and increases active Caspase-3 & 7. Mechanistically, inhibition of miR-15a increases inflammatory cytokines, activates caspase-1 inflammasome and increases Gasdermin D, an effector of pyroptosis. Importantly, both systemic and vascular-targeted delivery of miR-15a inhibitor decreases angiogenesis and tumor growth in a CT26 murine colorectal carcinoma model. Taken together, our findings highlight a novel role for miR mediated regulation of SMPD1 during radiation responses and establish proof-of-concept that this pathway can be targeted with a miR inhibitor.
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http://dx.doi.org/10.1038/s41598-020-62621-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101391PMC
March 2020

Non-English language validation of patient-reported outcome measures in cancer clinical trials.

Support Care Cancer 2020 Jun 18;28(6):2503-2505. Epub 2020 Mar 18.

The University of Texas MD Anderson Cancer Center, 1400 Pressler St, Unit 1422, Houston,, TX, 77030, USA.

Patient-reported outcome measures (PROMs) are increasingly incorporated as endpoints in oncology clinical trials but are often only validated in English. ClinicalTrials.gov was queried for cancer-specific randomized control trials (RCTs) addressing a therapeutic intervention and enrolling primarily in the USA. Peer-reviewed validation of Spanish and Chinese versions of each PROM was assessed. Of 103 eligible trials, a PROM was used as a primary endpoint in 25 RCTs (24.3%) and as a secondary endpoint in 78 RCTs (75.7%). A total of 61 of the 103 eligible trials (59.2%) and 17 of the 25 trials with a PROM primary endpoint (68.0%) used a PROM with either no Spanish or Chinese validation. The absence of validated PROM translations may diminish the voices of non-English language speaking trial participants. With an increasingly diverse US population, validation of non-English PROM translations may decrease disparities in trial participation and improve generalizability of study results.
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http://dx.doi.org/10.1007/s00520-020-05399-9DOI Listing
June 2020

Management of Muscle Invasive Bladder Cancer with Bladder Preservation in Russia: a Survey-Based Analysis of Current Practice and the Impact of an Educational Workshop on Clinical Expertise.

J Cancer Educ 2020 Mar 4. Epub 2020 Mar 4.

N.N. Blokhin Russian Cancer Center, Moscow, Russia.

Trimodality bladder preservation (BP) is an accepted alternative to radical cystectomy for patients with muscle invasive bladder cancer (MIBC). The global utilization of BP is variable, and practice patterns have not been previously studied in Russia. We sought to elucidate the contemporary BP practice patterns in Russia and determine the impact of the BP workshop on attitudes of Russian radiation oncologists (ROs) towards BP. The workshop was focused on patient workup, selection for BP, chemotherapy choices, radiation therapy (RT) contouring and planning, patient counseling. A total of 77 pre- and 32 matched post-workshop IRB-approved surveys, based on the workshop content, were analyzed using descriptive statistics to determine baseline clinical experience and patterns of care. The impact was judged by changes in participants' responses. A total of 56% of respondents had experience with delivering bladder-directed RT, and 60% of those treated both operable and inoperable MIBC patients. Only 10% felt uncomfortable offering an operable patient BP modality. Prior to the workshop, almost half of respondents estimated universal poor bladder (44%) and erectile functions (47%) after BP. The workshop resulted in dramatic change in participants' attitudes towards long-term urinary (Stuart-Maxwell test, p < 0.01) and sexual (exact McNemar test, p < 0.01) side effects. Prior to the workshop, only 47% of respondents routinely discussed smoking cessation (SC) with their patients, whereas after workshop, 88% agreed that SC discussion is mandatory (exact McNemar test, p = 0.04). BP for MIBC is commonly used in Russia. Our workshop resulted in dramatically improved understanding of long-term BP toxicities and inspired Russian ROs to incorporate SC counseling into routine clinical management.
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http://dx.doi.org/10.1007/s13187-020-01728-yDOI Listing
March 2020

Real-world applications of deep convolutional neural networks in diagnostic cancer imaging.

Chin Clin Oncol 2020 Dec 1;9(6):82. Epub 2020 Feb 1.

Radiation Medicine, Oregon Health & Science University, Portland, OR, USA; Hospital & Specialty Medicine, VA Portland Healthcare System, Portland, OR, USA.

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http://dx.doi.org/10.21037/cco.2020.01.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880057PMC
December 2020