bluuebunny/crossref_metadata_2025 huggingface dataset:
EROS: Engendering reproductive health within oncologic survivorship—ECOG-ACRIN E1Q11 paradoxical provision of reproductive health.
Authors: Patel Ashlesha , Lee Ju-Whei , Zaren Howard A. , Radeke Erika K , Lerner Rachel E. , Fukui Jami Aya , Makower Della F. , Tamkus Deimante , Rowland Kendrith M. , Adler William M. , Throckmorton Alyssa , ghamande sharad A. , Croley Jessica Jones , Pippas Andrew William , Qamar Rubina , Fisch Michael Jordan , Cella David , Wagner Lynne I. , Hackney Mary Helen Helen
Published: June 2024

11123

Background: For the 10% of women diagnosed with cancer in the reproductive age, reproductive health (RH) is a critical component of oncologic survivorship. RH includes oncocontraception (OC), oncofertility (OF) and sexuality. Guidelines segregate these components resulting in fragmented reproductive health care management. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. Intervention included RH didactics and decision aids. Childbearing interest was dichotomous, not completed childbearing (including either pregnant or future childbearing interest) or completed childbearing. The objective of this study is to determine provision of OC and OF referral by providers at the baseline visit based on patient’s self-reported childbearing interest at study entry. Chi-square tests were used to compare distribution differences in the referral status (receipt: yes vs. no) between treatment arms. Results: The EROS study enrolled 420 subjects. Of the 63.6% (267/420) completed childbearing, 62.4% (58/93) in the intervention arm and 40.2% (70/174) in the non-intervention arm received an OC referral (p=0.0006), whereas 98.9% (92/93) in the intervention arm and 93.7% (163/174) in the non-intervention arm received an OF referral (p=0.0487). Of the 36.4% (153/420) not completed childbearing, 48.3% (28/58) in the intervention arm and 33.72% (32/95) in the non-intervention arm received an OC referral (p=0.0729), while 77.6% (45/58) in the intervention arm and 70.5% (67/95) in the non-intervention arm received an OF referral (p=0.3388). Conclusions: While the intervention increased the rates of provision of oncocontraception and oncofertility for patients with completed childbearing, our study shows provision of oncofertility referrals at a markedly higher rate than oncontraception. Referral patterns were inconsistent with patient need particularly in completed (receiving OF referral) or delayed childbearing (not receiving OC referral) interest of the patient. The bias favoring oncofertility referral may reflect oncology guidelines emphasizing this aspect of reproductive health despite comprehensive needs of patient.
Unstructured EMR data hold the key to oncology studies: Methods for validating NLP-extracted phenotypes from EMR notes.
Authors: Eldridge Elizabeth H. , Trowbridge Elizabeth , Van Zandt Mui , Adam Atif , Mack Christina D.
Published: June 2024

11133

Background: Natural language processing (NLP) parsers are advanced algorithms designed to parse values of interest from free-text stored in Electronic Medical Records (EMR). Given the importance of information stored in free-text for use in oncology research, it is crucial to understand how accurately NLP algorithms are extracting oncology-specific measures of interest. We focus on validating NLP-parsers that identify three measures critical to oncology research by evaluating how closely the NLP-parser results match manual chart abstractor review: AJCC summary cancer stage group (cancer stage), AJCC TNM stage (TNM stage), and surgical treatment of cancer (surgery). Methods: Following deployment of the parsers on 8,000 non-identifiable free-text notes housed in an aggregated non-identifiable U.S. EMR database, manual chart abstraction was performed on a random selection of notes (n=300) dated between 2008 to 2023 to validate the parsers’ accurate capture of cancer stage, TNM stage, and surgical treatment of cancer. We report true positives (TP), false positives (FP) and positive percent value (PPV). Results: The PPV of AJCC Cancer Stage was 99.0% (n=297 TP, n=3 FP). The PPV of the TNM stage NLP-parser was 97.3% for tumor stage (n=292 TP, n=8 FP), 99.0% for nodal stage (n=297 TP, n=3 FP), and 96.7% for presence of metastases (n=290 TP, n=10 FP). The PPV of the surgery parser was 87.8% (n=468 TP, n=65 FP). Conclusions: These NLP-parsers performed very well identifying the measures of interest, providing confidence in use of these derived measures which are central to oncology research. Validation is a necessary initial step in processing real-world data for use in real-world evidence generation, with unique considerations needed in the oncology research space due to key information being documented in EMR free-text rather than structured data fields.
Analysis of healthcare provider management of immune-related adverse events and concordance with NCCN Guidelines.
Authors: Rosenthal Kristen M. , Cartwright Megan , Andrie Rachael , Thompson John A.
Published: June 2024

11136

Background: Immune checkpoint inhibitors (ICIs) are a mainstay of treatment for many cancers but can cause immune-related adverse events (irAEs) that require prompt recognition and management. In 2017, we developed an online interactive decision support tool [www.clinicaloptions.com/immuneAEtool] for healthcare providers (HCPs) with case-specific recommendations for managing irAEs from a medical oncology expert. In 2019 and 2023, we updated the tool to offer recommendations from the latest National Comprehensive Cancer Network (NCCN) Guidelines. Here, we report a comparison of self-reported irAE management from HCPs using the 2023 tool vs NCCN recommendations and a comparison of practice patterns between the 2023 and 2019 tools. Methods: To use the online tool, HCPs entered the affected organ system, symptom grade/severity, and their planned management strategy. The tool showed the NCCN management recommendation for that irAE and then asked if the recommendation changed their intended management approach. Results: From July to December 2023, 172 HCPs entered 241 case scenarios into the tool; 53% treated <10 patients/month with ICIs, and 38% of HCPs practiced in the United States. The most common irAEs involved the gastrointestinal (GI)/hepatobiliary (hep)/pancreatic (29% of cases) or dermatologic/oral (19%) systems. Overall, the planned irAE management strategy of HCPs matched the NCCN recommendations in 55% of cases, an increase from the 49% concordance rate in our 2019 analysis. In the current analysis, the lowest concordance was observed for infusion-related reactions (20%), musculoskeletal irAEs (46%), and dermatologic/oral mucosa irAEs (46%; Table). Furthermore, US HCPs had a lower overall concordance rate (46%) than non-US HCPs (66%). Approximately one half (56%) of all HCPs indicated that the NCCN recommendations in the tool changed their management plan. Conclusions: These data suggest that many HCPs are challenged to optimally manage irAEs and are not managing their patients in concordance with NCCN guidelines. A detailed analysis of HCP irAE management vs NCCN recommendations, including by organ system and severity, along with a comparison of 2023 vs 2019 practice patterns, will be presented. [Table: see text]
Developing a deep learning algorithm to support decision making for the classification of microsatellite instability (MSI) in cancer, using artificial intelligence(AI).
Authors: Pombo Maria Teresa , Chirkes Julieta , Erbetti Andrea , Sanguinetti Olivia , Perez Adrian , Paschetta Federico , O'Connor Juan Manuel , Gorodisch Ana
Published: June 2024

11152

Background: Digital pathology (DP) is an image-based environment, which allows the acquisition, and interpretation of pathological information from a digitized slide. The objective of this work was to build an AI model for predicting MSI in endometrial, colorectal, and gastric carcinomas, to simplify laboratory processes, in a developing country. Nowadays, it is crucial to recognize patients who will respond to treatments such as immunotherapy. Methods: The computational tool utilized was CLAM (clustering-constrained-attention multiple instance learning). This architecture developed by Lu et al. is a deep learning method that utilizes weak supervision and attention based learning, to identify the most relevant regions for tumor classification, in whole slide images (WSI). CLAM was designed to excel in tumor subtyping tasks which are discernible to human visual perception. We are challenging this architecture by employing it in the detection of a molecular phenomenon. For training and internal evaluation, images from TCGA and CPTAC were obtained for endometrial cancer (EC). For colorectal (CCR) and gastric cancer (GC), only images from TCGA. Archived histological samples with MSI/MMR status from a donor lab , were used for external validation. Results: Tests conducted on an internal cohort of 58 samples for CCR and GC revealed a sensitivity of 76.9%, a specificity of 78.1%, and an AUC-ROC of 76.3%. In the case of EC, where 38 cases were evaluated, the sensitivity was 100%, specificity was 68%, and AUC-ROC reached 92%. Notably, regarding the externalcohort consisting of 109 samples, both models demonstrated a high sensitivity of up to 90% in recognizing positive cases. Due to the models’ specificity (approximately 45%), it was not possible to accurately predict MSS samples in all three types of tumors. Conclusions: Promising results were obtained for the first approach in detecting molecular biology events, such as MSI, using AI. CLAM is a useful platform for digital pathology, but new validations are needed to enhance our work and strengthen the model. It is hypothesized that CLAM may not be the best tool for AI in identifying molecular biology events, so other directions are being explored. For external cohorts, preanalytical changes play an important role in obtaining accurate results with scanners and digitalization. It is crucial to teach healthcare professionals about AI in order to ensure its availability, in every diagnostic laboratory.
Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL).
Authors: Krackeler Margaret , Chee Bryant , Orchanian Arthur K , Law Lisa Y. , Lopez Alfredo R. , Buchanan Susan , Maglinte Gregory A. , Liu Raymond , Zhu Zheng , Sakoda Lori C. , Tavakoli Jahan
Published: June 2024

11158

Background: Zanubrutinib (zanu) is a next-generation selective Bruton’s tyrosine kinase inhibitor (BTKi) with superior efficacy over first generation ibrutinib (ibru) in CLL/SLL patients (pts). Herein we present real-world treatment patterns based on a formulary change from ibrutinib to zanubrutinib in pts with CLL/SLL in an integrated community oncology practice. Methods: We retrospectively analyzed CLL/SLL pts 18 years and older who received at least 3 months of zanubrutinib from October 1, 2018 to September 15, 2023 at Kaiser Permanente Northern California. Treatment patterns, treatment-emergent adverse events (TEAEs: AEs reported during BTKi use), treatment-limiting adverse events (TLAEs: AEs leading to BTKi discontinuation), and mortality were reported. Results: A total of 281 pts received zanu (median age: 71 years; 64% male); 190 pts switched from ibru (ibru-zanu), and 91 pts received zanu only. Most pts were White (75%) followed by Black (10%). Compared with ibru-zanu pts, zanu-only pts were older (median age 74 vs 69 years) and had more comorbidities but were comparable in sex, race, and insurance type. The primary reasons for switching to zanu were formulary change (73%) and progression (15%). Median follow-up time after initiation of first BTKi was longer in the ibru-zanu group (Table). Similar TEAE rates were seen with use of both BTKi therapies, with lower TLAE rates with zanu (Table). Most common TLAE were atrial fibrillation and fatigue for ibru, and cytopenias and rash/bruising for zanu. Cardiac TLAE and non-TLAE rates overall were higher with ibru than zanu, and the rates decreased while on zanu after switching from ibru (Table). Dose modification occurred in 34 pts on ibru and 50 pts on zanu (18 ibru-zanu pts, 32 zanu-only pts), with reductions primarily for grade 1-2 AEs. Of the 281 pts who received zanu, 79% remain on treatment at the end of data collection; 13 pts died (8 from infection, including 5 from COVID), with no reports of treatment-related deaths. Conclusions: In the real-world setting post-formulary change, zanu is effective and safe in pts with or without prior ibru use. Zanu use had lower cardiotoxicity and TLAE rates than ibru though data was limited by a difference in follow-up time. Similar results were seen in zanu-only pts despite being older and having more comorbidities, with discontinuation most often due to grade <3 AEs. [Table: see text]
The benefit of chart curation of electronic health record (EHR) data: Comparing data completeness between curated and structured data.
Authors: Blanc Simon , Rui Anna , Vasudevan Anupama , Gart Mike , Sura Teena , Morgan Erin , Varughese Prateesh , Mena-Allauca Mercedes , Scott Jeffrey A.
Published: June 2024

11165

Background: The main objective of an EHR is to effectively standardize clinical workflow. However, EHR data is also utilized extensively as secondary data for clinical research and quality improvement. Healthcare data exists in different forms such as paper, digital images, and notes, only some of which are recorded as structured data in the EHR. It is therefore essential to curate detailed information from unstructured data so that the patient’s journey can be understood in depth for research and quality studies. Methods: Patients diagnosed with metastatic breast cancer (mBC) between 01-Jan-2020 and 31-Dec-2022 were identified from the Integra Connect PrecisionQ de-identified database of 3 million cancer patients across 500 sites of care across ~80% community oncology and ~20% academic practices. Manual curation was conducted for a sample of these patients and the fill rates of crucial elements were captured as part of this study. Results: A total of 13,763 mBC patients were identified during this study period. The availability of data for the different variables was assessed from structured data in 13,120 patients. Additional information was obtained by manual curation for 643 patients. Information on staging and grade were available for 62.8% in the structured data, while curation increased the availability of these details to 99.5% among those 643 patients. The fill rates for patients’ tumor size and nodal status, as defined by the T and N values, were found to be 99% in the curated data compared to 60% in the structured data. Similarly, the fill rates were more than 98% for estrogen, progesterone, and HER2 receptor by curation, while they were only approximately 65% in the structured data. HER2 low, HER2-ve, and HER2+ve status was identified in 8%, 45.2%, and 10.1% by structured data and in 57.1%, 84.1%, and 14.0%, respectively, by curated data. Furthermore, the fill rates via curation were 97.1% for HER2 immunohistochemistry tests compared to 49.0% for structured data, while the fill rates for in-situ hybridization (ISH) or fluorescent in-situ hybridization (FISH) tests were 61.3% for curated data compared to 28.4% for structured data. This discrepancy is caused by the fact that IHC and FISH/ISH tests are primarily found only in PDF format. Conclusions: This study highlights the need for curation in order to maximize the utilization of EHR data for secondary research purposes and quality studies. Natural language processing and augmented curation methods can further enhance the quality of EHR data for secondary research.
Fragility index analysis of systemic therapy clinical trials in soft tissue sarcoma (STS).
Authors: Braik Dina , Wilson Brooke , Abdul Razak Albiruni Ryan , Salawu Abdulazeez
Published: June 2024

11581

Background: The fragility index (FI) measures the robustness of randomized clinical trials (RCT) that have positive results based on statistical p-values. It estimates the minimum number of events that are needed to reverse the trial results from positive to negative. Here, we perform FI analysis on RCTs evaluating systemic treatments for STS. Methods: A systematic search of the Medline and Embase databases for RCTs in adults with advanced STS (Jan 1998 to Dec 2023) was conducted. Gastrointestinal stromal tumor trials were excluded. The FI framework was adapted to allow the use of time-to-event (TTE) outcomes – progression-free survival (PFS) or overall survival (OS) as previously described (Desnoyers et al 2021). Survival tables were reconstructed from published data on positive TTE outcomes, using the Parmar Toolkit. Positive secondary endpoints were used only if the primary endpoint was negative. The number of additional events that would result in a non-significant effect for the hazard ratio (HR) of the positive endpoint of each trial (FI) was calculated and expressed as a proportion of the size of the experimental arm (fragility quotient; FQ). The number of censored patients – those who withdrew consent or were lost to follow-up (Cn) was noted. Results: Among 47 RCTs, 16 (8 phase II; 8 phase III) trials had positive outcomes. The primary endpoint was positive and used for FI analysis in 11/16 trials (68.8%). PFS was the most common positive outcome, evaluated in 13 trials (81.3%). The median FI was 6 (range 2 – 52), with FI < 10 observed in 11 trials (68.8%). Median FQ was 7% (range 1 – 59%) and 10 trials (62.5%) had FQ < 10%. Among 14 trials that reported data, Cn was ≥ FI in 7 trials (50%). Only 2 of 4 trials (50%) that led to regulatory approval had FI > 10 or FQ > 10%. Of the other 2, one drug approval was subsequently withdrawn (Table). Conclusions: Most positive clinical trials in STS were fragile and their outcomes may be confounded by the level of censoring. Real-world evaluation of approved systemic therapies and value scales such as ESMO Magnitude of Clinical Benefit scale or ASCO value framework are needed to confirm clinical benefit of systemic treatments in STS.[Table: see text]
Systemic therapy in NF-1 associated malignant peripheral nerve sheath tumors (MPNST).
Authors: Munnangi Pujita , King Bridgette L , Chiang Y. Sabrina , Conley Anthony Paul , Araujo Dejka M. , Livingston J. Andrew , Ludwig Joseph Aloysius , Nakazawa Michael , Nassif Haddad Elise F , Ravi Vinod , Ratan Ravin , Zarzour Maria Alejandra , Patel Shreyaskumar , Torres Keila E , Somaiah Neeta
Published: June 2024

11583

Background: MPNST are rare sarcomas that have a poor prognosis and are challenging to treat. Around 50% of MPNSTs are associated with NF1, 40% are sporadic, and 10% are radiation-associated. Doxorubicin (D) based chemotherapy (CT) regimens are commonly used in the front-line, and combinations have better response rates than single agents. Response to second-line regimens is not well documented. The objective of this study is to document efficacy of systemic regimens in MPNST as a benchmark for future novel therapeutics in this space. Methods: 72 patients (pts) with NF1-associated MPNSTs in an MD Anderson database were reviewed retrospectively from EMR. Variables collected included demographics, primary MPNST location, localized vs metastatic, and treatments received (+/- radiation, +/-surgery, +/- lines of CT). Responses (progressive disease (PD), stable disease (SD), partial response (PR)) as interpreted by treating physician and radiology reports and time on treatment for 1st and 2nd line chemotherapy regimens were assessed. Cox proportional-hazard regression was used to investigate associations of variables with overall survival (OS: from time of diagnosis to death or last follow-up). Results: Demographic and CT details are provided (Table). The median age at diagnosis was 34.5 yrs (range: 9-71). The most common MPNST location was the trunk (56.94%). D based regimens were the most frequent 1st-line CT (65.7%), and gemcitabine- docetaxel was the most frequent 2nd-line CT (33.3%). In pts with metastases, 74.4% got 1st line, 44.7% 2nd line, 25.5% 3rd line, and 12.7% got 4th line therapy. Median follow-up was 2.46 yrs (IQR 1.24-9.52). The median time on treatment for 1st and 2nd line CT was 110 (IQR 48-153) and 57 (IQR 41-133) days, respectively. In the multivariate COX model for the entire cohort, male sex (HR: 0.35, 95%CI: 0.18-0.68), lower extremity primary (HR: 0.09, 95%CI: 0.02-0.40), and absence of metastases at last follow up (HR: 0.05, 95%CI: 0.02-0.17) were associated with decreased risk of death. Additional analysis on efficacy and survival of the systemic therapy regimens will be presented at the meeting. Conclusions: In this study < 50% pts with advanced NF1 related MPNST made it to 2nd line CT and outcomes were inferior to the predominantly D based 1st line regimens. This highlights an area of high unmet need. [Table: see text]
Off-label use of fam-trastuzumab deruxtecan-nxki with early activity in a cohort of patients with desmoplastic small round cell tumor.
Authors: Slotkin Emily K , Burke Chelsey , Hameed Meera , Antonescu Cristina R. , Agaram Narasimhan P , Bhanot Umesh , Behr Gerald , Price Anita , Pandit-Taskar Neeta , Domenico Dylan , Glade Bender Julia Lynne , Dela Cruz Filemon S , Reed Damon R.
Published: June 2024

11584

Background: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive sarcoma occurring predominantly in pediatric, adolescent and young adult biologic males, and is molecularly characterized by the pathognomonic EWSR1-WT1 fusion. Despite aggressive multi-modality therapy outcomes for those with DSRCT remain poor, and more effective therapies are urgently required. Prior pre-clinical data and transcriptomic analyses of DSRCT patients has suggested the relevance of the ERBB2 pathway in this disease, prompting the off-label use of fam-trastuzumab deruxtecan-nxki (T-DXd) in the treatment of patients of DSRCT patient with relapsed and refractory disease. Methods: Patients with relapsed/refractory DSRCT received T-DXd 5.4 mg/kg intravenously in 21-day cycles. Whole body PET and CT of the chest, abdomen and pelvis were used for monitoring. Response was correlated with HER2 immunohistochemistry (IHC) status and transcriptomic analysis by RNA sequencing (RNAseq) when available. Results: Seven patients received the agent, and at the time of submission 3 patients had at least one follow up imaging test after receiving between 6 and 9 cycles of T-DXd. Treatment was overall well tolerated with the only grade 3 toxicity of transaminitis (in patients with known liver metastases), which self-resolved. All other toxicities including constipation, nausea, and fatigue were grade 2 or less. All 3 patients have experienced clinical benefit including one patient with a RECIST 1.1 partial response and two patients with stable disease. Additionally, favorable responses were noted by PET imaging. Four additional patients with relapsed/refractory DSRCT have initiated off-label treatment with T-DXd and are pending imaging responses. 7/7 and 4/7 patients have available IHC and ERBB2 RNA expression data available respectively. All ERBB2 RNA expression data is elevated when compared with the median across all evaluated pediatric tumors in our institutional series. Conclusions: The use of anti-HER2 therapy in a limited and unselected group of heavily pre-treated DSRCT patients is demonstrating an early signal of activity with minimal toxicity and suggests that formal assessment as monotherapy or in other relevant combinations in clinical trials is warranted. Further correlation with IHC and RNAseq expression data may help optimize correlatives and/or generate biomarkers for future clinical trials.
Patient-reported symptom interference with activity- and mood-related functioning prior to start of an early-phase oncology combination trial including immune checkpoint blockade.
Authors: George Goldy C , Piha-Paul Sarina A. , Dumbrava Ecaterina Elena , Subbiah Vivek , Fu Siqing , Tsimberidou Apostolia Maria , Pant Shubham , Appleton Grace , Noor Laila , Yap Timothy A. , Rodon Ahnert Jordi , Meric-Bernstam Funda , Cleeland Charles S , Mendoza Tito R. , Hong David S.
Published: June 2024

12084

Background: We examined symptom interference with activity- and mood-related functioning at baseline in early-stage trials of combination treatments that included at least one immune checkpoint inhibitor, and its association with quality of life (QOL)-, clinical-, and trial-related factors. Methods: Patients scheduled to begin an early-phase trial of a combination treatment with immune checkpoint blockade, and who had not received trial-related treatment were recruited into a prospective longitudinal study design (NCI R01CA242565), and completed the following validated patient-reported outcome (PRO) measures prior to trial start: MD Anderson Symptom Inventory- Immunotherapy (score range: 0-10, higher scores = worse symptom interference); NCI’s PRO Common Terminology Criteria for Adverse Events (0-4, higher = worse severity); EuroQoL-5 dimensions assessing health status (0-100, higher = better health) and problems with self-care, and the Sloan Global QOL scale (0-10, higher = better QOL). Statistical tests included Spearman’s correlation rho (r) and multivariable linear regression. Results: 977 baseline PRO measures were completed by 247 patients (median age = 59 y; 46% female). Worst symptom-related interference was with activity (3.0 on a 0-10 scale), work (2.9), and enjoyment of life (2.4). Composite score means were 2.8 for symptom interference with walking, activity, and work (WAW; activity-related functioning), and 2.1 for interference with relationships, enjoyment of life, and mood (REM; mood-related functioning). Symptoms most associated with worse WAW were fatigue (P<0.001) and appetite loss (P=0.001). Worse WAW was linked to worse REM (r=0.78, P<0.001). Diminished sexual interest/mood (DSI) was associated with worse WAW (r=0.35, P<0.001) and REM (r=0.33, P<0.001). Worse WAW was linked to shorter trial duration (P=0.003) and worse response (progression of disease/immune-related progression) on the clinical trial (P=0.05). Conclusions: This first, comprehensive and prospective examination of symptom interference with functioning at trial baseline found that worse symptom interference was linked to worse QOL, poorer clinical outcomes, and shorter trial duration. These findings suggest that baseline patient-reported symptom interference with functioning can serve as a potential biomarker of poor prognosis in investigational trials, and that trial patients may benefit from initiation of supportive care prior to trial start. [Table: see text]
Prescribers of opioids for head and neck cancer (HNC) survivors.
Authors: Salz Talya , Mishra Meza Akriti , Bradshaw Patrick T , Jinna Sankeerth , Moryl Natalie , Kriplani Anuja , Tringale Kathryn Ries , Flory James , Korenstein Deborah , Lipitz-Snyderman Allison
Published: June 2024

12085

Background: Older HNC survivors often experience post-treatment pain, and they have concerningly high rates of unsafe opioid prescribing per CDC guidelines (e.g., high doses, concurrent benzodiazepines). Because interventions to improve opioid safety should target providers who prescribe opioids to HNC survivors, we aimed to identify post-treatment opioid prescriber specialty. Methods: Using the national linked Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data, we identified adults age >65 diagnosed 2014-2017 with stage I-III HNC and who had ≥6 months treatment-free follow-up prior to censoring at further treatment, new cancer, hospice, death, or end 2019. Each opioid fill was assigned to a prescriber specialty: oncology (medical, radiation), surgery, primary care (internal medicine, family practice, geriatrics), pain, or other. Prescriber patterns (number of fills, duration of fill, annual opioid receipt) were summarized across follow-up and stratified by year. Multinomial logistic regression models captured trends in prescribing, accounting for clinical and sociodemographic characteristics. Results: Among 5547 HNC survivors, 2951 (53%) had ≥1 opioid fill (median 2.1 years follow-up). Primary care providers (PCPs) prescribed 49% of all fills (46%-53% each year). PCPs prescribed opioids to 49% of survivors with ≥1 opioid fill, a greater share than other specialties. PCPs prescribed longer supplies of opioids (median 30 days/fill and median 45 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncologist or surgeon was ≥5 times lower than by a PCP. Over follow-up, rates of opioid prescribing by oncologists decreased relative to rates of prescribing by PCPs (Table). Conclusions: Primary care involvement in opioid prescribing remains high over post-treatment HNC survivorship. Interventions to address unsafe opioid prescribing for HNC survivors should target the primary care setting, as is typical for opioid-reduction efforts in the non-cancer population. [Table: see text]
Multidisciplinary PAIN management features of pediatric oncology patients in a pediatric cancer center in Turkiye: A developing country experience.
Authors: Tacyildiz Nurdan , Incesoy Ozdemir Sonay , Canakci CEM , Yigit hande Irem , Maharramova Vafa , Dincaslan Handan , Unal hanzade Aybüke , Asik Ibrahim , Ozgencil Enver , Unal Emel Cabi
Published: June 2024

e22002

Background: Pain is one of the most important problems that affects more than half of cancer patients at any stage of the disease and disrupts the quality of life of patients. The aim should be to relieve pain as soon as possible and prevent its recurrence. In this study, we aimed to evaluate the clinical characteristics of our patients who were followed up with a diagnosis of cancer in our clinic and whose pain management was planned in a multidisciplinary manner with the department of Algology. The clinic where the study was conducted is the reference center of a middle income developing country. Therefore, the data obtained will represent the characteristics of developing countries. Methods: In this retrospective descriptive study, patients followed up with diagnosis of cancer at Ankara University Faculty of Medicine, Department of Pediatric Oncology between 2018 and 2023 and consulted to Department of Algology for pain management were included. Patients whose file information could not be accessed from the hospital information system were excluded from the study. Demographic and clinical parameters of the patients were recorded. The data were evaluated with descriptive statistical methods appropriate to distribution. Results: A total of 33 patients, 19 girls and 14 boys, aged between 2.2 and 23.5 (median 14.4) were evaluated in the study. For each case, a median of 2 (1-16) consultations were made. The most frequent cancer diagnosis was bone tumors with 42% (n:14). Nociceptive pain was present in 25 of the patients, nociceptive and neuropathic pain were present together in 8 patients. It was determined that the most commonly used treatment for pain management was paracetamol, which was used in all patients. Other agents used, in order of frequency: Fentanyl in 19 (57.6%) of the patients, NSAID in 13 (39.4%), gabapentin in 9 (27.3%), oxycodone in 12 (36.4%), 7 (3%) 21.2) were tramadol, 4 (12.5%) were morphine, and 1 (3%) was codeine-paracetamol. Intravenous patient-controlled analgesia (PCA) was used in one patient. Side effects were observed in 3 patients. Fentanyl-related constipation was observed in 1 patient, fentanyl-related globe vesicale was observed in 1 patient, and thrombocytopenia was observed in 1 patient due to gabapentin. Conclusions: Pain is an important factor affecting the quality of life and treatment compliance of children with cancer. Therefore, it is important to ensure effective treatment and to raise the awareness of physicians and care providers by keeping it constantly on the agenda especially in developing countries. Prospective studies will be most useful guide for clinicians.
Clinical and histological profiling of triple-negative breast cancer at Chihuahua´s state cancer center: An observational study.
Authors: Baylon Valdez Victor , Gonzalez-Gonzalez Luisa F , Zamudio Lozoya Enrique Jose , Ochoa-Elizondo Patricio , Mendoza-Muraira Paolo , Martinez-Garcia Lascurain Regina , Martinez-Sanciprian Rafael , Bates Rodriguez Valeria , Mares García América Susana , Reza Bravo Gustavo Gil , Gonzalez Mendoza Rene Lazaro
Published: June 2024

e22529

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. This subtype is associated with a poorer prognosis and higher recurrence rates compared to other breast cancer subtypes. Understanding the histopathological and clinical characteristics of TNBC is crucial for improving early detection, clinical management, and treatment outcomes. In this context, a descriptive analysis was conducted to explore the association between TNBC and histological grade, histopathological type, and clinical stage at the State Cancer Center. Methods: A retrospective, single-center study was conducted at Chihuahua's State Cancer Center, where medical records of patients aged ≥ 18 years old diagnosed with TNBC between January 2018 and December 2022 were retrospectively reviewed. Data related to weight, histological grade, histopathological type, and clinical stage at TNBC diagnosis were collected. Frequency analysis was performed to determine the distribution of these characteristics in the TNBC patient population. Additionally, the association between histological grade and clinical stage at diagnosis was examined using appropriate statistical tests. Results: During the study period, 753 patients were diagnosed with breast cancer. Of these, 84 (11%) were diagnosed with triple-negative breast cancer and were included in the study. The mean age was 49 ± 13 years, with a mean BMI of 28 ± 5. The most common histologic subtype in this group was invasive ductal carcinoma, accounting for 78 (93%) of the TNBC cases. At the time of diagnosis, 19 (23%) were diagnosed with stage IIA, 17 (20%) with stage IIIA, 9 (11%) with stage IV, and 4 (5%) were detected in situ. Overall, the majority were identified as grade 3 tumors (44; 52%). Finally, within the stage IIA group, the majority were grade 3 tumors (58%). Conclusions: As seen in other cohorts, we found a similar frequency of TNBC among patients with breast cancer in our facility in the northwest of Mexico. The distribution of clinical stages highlights the varying degrees of disease progression at the time of diagnosis, with a considerable portion presenting at advanced stages. Moreover, these insights underscore the urgent need for improved screening strategies and early detection methods.
Pathogenic germline variants among Thai patients with colorectal cancer: A study in Genomics Thailand Project.
Authors: Roila Nutdanai , Pithukpakorn Manop , Thuwajit Chanitra , Trakarnsanga Atthaphorn , Chantharasamee Jomjit
Published: June 2024

e22534

Background: Germline variant testing in colorectal cancer (CRC) patients (pts) has been applied in many countries. Limited data is known regarding germline CRC prevalence in Thailand and other low to middle-income countries in Southeast Asia. Identifying the variants in different ethnicities may show the variety in frequency of the pathogenic germline variants (PGVs) and their relationship with clinical characteristics. Our study reports on the distribution of PGVs and their clinical findings in Thai CRC pts. Methods: We use the germline testing results from the Genomics Thailand Project during 2020-2023, which performed next-generation sequencing on 50,000 pts in 5 disease groups. CRC pts in our institution with a potential risk of carrying PGVs were sent to a geneticist to obtain a family history prior to undergoing germline testing with 25-96 cancer-predisposing genes. Pts with complete pedigree data and germline testing results were enrolled in our retrospective cohort to analyze the variants and clinical findings from chart reviews. Descriptive statistics, the Cox proportion hazards model, and the Kaplan-Meier method were used to evaluate the results. Results: We included 137 CRC pts with a mean age of 47 years at diagnosis, and 58.4% were male. Of these, 38/137 (27.8%) pts were identified as pathogenic/likely pathogenic(P/LP). 26/38 (68.4%) were pathogenic Lynch syndrome (LS), 16 (42.1%) MLH1, 6 (15.8%) MSH2, 2 (5.3%) MSH6, and 2 (5.3%) PMS2. Among pathogenic non-LS, the most frequent variant was 4 (10.5%) APC, followed by 3 (7.9%) ATM, 2 (5.3%) BRCA2, 1 (2.6%) PTEN, 1 (2.6%) BARD1, and 1 (2.6%) monoallelic MUTYH. The LS group was significantly associated with a family history of CRC (p < 0.001), endometrial cancer (p = 0.001), and a synchronous/metachronous CRC (p = 0.003) compared to the non-PGVs group. Likewise, the presence of CRC in a first-degree relative (p = 0.025), more than one CRC pts in the family (p = 0.027), or early onset CRC (p = 0.012) in a first-degree relative was also significantly higher in the pathogenic non-LS group compared to the non-PGVs group. CRC pts who had more than one primary cancer in a lifetime were not significant in the LS or non-LS group compared to the non-PGVs group. At a median follow-up time of 60 (range 7-453) months, Pts in the PGVs group tended to have a shorter median time from the first CRC diagnosis to a second event defined as any of metachronous/synchronous CRC, recurrent CRC, or second cancer in a different organ compared to the non-PGVs group (135 vs. 228 months, p = 0.11). Conclusions: 27.8% pts in our cohort carried P/LP germline variants. The PGVs group was associated with a shorter time to the second event and a higher rate of familial cancer. Our study supports the benefits of genetic cancer screening. [Table: see text]
Defeating cancer through education, prevention, and youth athletics.
Authors: Barrett William , Anderson Sherwin , Frankart Andrew , Thompson Samuel , Mackey William
Published: June 2024

e22548

Background: Barriers to effective scientific learning exists for elementary students, particularly in socially and financially disadvantaged settings. Maintaining interest, concentration and focus can be difficult for children, particularly when confronted with complex material and multiple distractions. Methods: We implemented a scientific educational program for children attending an urban community center after-school program entailing tutoring stations conducted during a basketball practice. Five tutoring stations included human physiology, astronomy, geography, geology and cancer. Five children spend 3 minutes with tutors who are medical students or residents while five other children are on the basketball court going through drills with a coach. After 3 minutes the kids on the court and the kids being tutored switch places. The sequence is repeated until each child has rotated through each of the 5 tutoring stations and through each of the 5 basketball drills. After this, each child rotates through each tutoring station for one minute where they are quizzed on what they were taught and the end of practice scrimmage begins with a score based upon each team of fives’ performance on the quiz. Results: The method proved to be highly effective in the children’s ability to understand and retain scientific concepts. Within weeks nearly every child could list the planets of the solar system in order, calculate their pulse and explain its importance, list the most common symptoms of the most prevalent cancers, correctly identify continents, oceans, countries and states on maps and explain the origin of volcanos, earthquakes, hurricanes and tsunamis. Conclusions: This novel teaching method proved highly effective with children being able to maintain interest, focus and concentration in a setting where physical exertion is rapidly alternated with educational instruction. Parents and teachers commented that the kids learned more in 45 minutes with this method than in 2 weeks of conventional classroom teaching. The approach is widely applicable to students from diverse backgrounds.
Associations between prognosis and primary endpoint selection in phase III oncology trials in the United States.
Authors: Uemura Nariaki , Ono Shunsuke
Published: June 2024

e23022

Background: Overall survival (OS) is commonly used as a primary endpoint in phase III oncology trials in the United States, serving as direct evidence of clinical benefit and as an objective outcome measure. Other endpoints such as progression-free survival (PFS) and objective response rate (ORR) are also utilized. Factors such as a cancer type and treatment line are considered important for primary endpoint selection, however, the fundamental factor influencing primary endpoint selection across various cancer types or treatment lines remains unclear. I hypothesize that the prognosis of the target patient population is one of the key fundamental factors across any groups in primary endpoint selection. This study aims to investigate the associations between the prognosis and the type of primary endpoint. Methods: All phase 3 clinical trials conducted in the US, focusing on drug therapies for cancer, between January 1, 2015 and Dec 31, 2022 were included. Multinomial logistic regression was utilized to assess the relationships between prognosis, indicated by the median overall survival of the control arm, and the type primary endpoint among OS, non-OS time-to-event endpoints (Other TTE), and response or remission rate (RR). Models were adjusted for cancer type, treatment line, the primary endpoint of the previous clinical study for the same target patient population, monotherapy, mechanism of action (MOA), biomarker for the drug, orphan drug designation (ODD), and accelerated approval (AA) before regulatory approval. Results: Out of 5,877 phase 3 clinical trials, 151 studies and 167 evaluation sets were included in the analysis. When the prognosis and the type of primary endpoint were tested, this factor demonstrated a statistically significant difference with a positive coefficient for Other TTE, RR, and a co-primary endpoint of OS and Other TTE compared to OS. The prognosis, the median OS of the control arm, was 10.5 months (95% CI 5.00-16.6) for OS, 18.5 months (95% CI 7.50-34.3) for Other TTE, 32.9 months for RR, and 13.6 months (95% CI 8.7-46.6) for the co-primary endpoint of OS and Other TTE respectively. No effect modification was observed for Other TTE and the co-primary endpoint of OS and Other TTE. Conclusions: A better prognosis is associated with the selection of surrogate endpoints in phase 3 oncology trials among many factors. The associations between the prognosis and the type of primary endpoint were observed for Other TTE and a co-primary endpoint of OS and Other TTE. These findings elucidate one of the fundamental factors for primary endpoint selection and emphasize the importance of prognosis in selecting a primary endpoint in phase 3 clinical trial in oncology in the US. However, further study is required to comprehensively understand the impact of RR on primary endpoint selection, as this analysis was limited by the lack of median OS data for RR.
Impact of frailty on hospitalized patients with prostate cancer: A retrospective analysis.
Authors: Patel Rushin , Patel Mrunal , Chitkara Akshit , Patel Zalak , Patel Darshil , Anamika Fnu , Onyechi Afoma
Published: June 2024

e23054

Background: The impact of Hospital frailty risk score on outcomes in hospitalized patients with prostate cancer has not been previously studied. This research aimed to examine the association between frailty and prostate cancer outcomes. Methods: This retrospective study utilized hospitalization data from the National Inpatient Sample (NIS) between January 1, 2020, and December 31, 2020. Data of patients with a primary or secondary discharge diagnosis of prostate cancer (ICD10-CM codes C61.0, D07.5, and Z85.46) were obtained. The objective was to evaluate the correlation between frailty and prostate cancer. Multivariate analysis was performed, stratified by race, age, Charlson index, median annual income in the patient's zip code, hospital bed size, teaching status, and census division of the hospital. Results: A total of 51,980 hospitalizations for prostate cancer were identified, with 72.7% in the intermediate to high frailty score (IHFS) group and 27.3% in the low frailty score (LFS) group. The IHFS group had a higher unadjusted in-hospital mortality rate than the LFS group (5.85% vs. 1.2%). Patients with IHFS had increased odds of adjusted mortality compared to those with LFS (adjusted odds ratio [aOR] = 4.45, 95% Cl [3.80-5.22], P < 0.01). Hispanic and Black race patients also had increased odds of adjusted mortality compared to Caucasian race patients (aOR = 1.42, 95%CI [1.19-1.70], P < 0.01); aOR = 1.16, 95%CI [1.00-1.32], P = 0.037, respectively). Additionally, the IHFS group had longer lengths of stay (5.65 ± 0.038 vs. 3.26 ± 0.28 days) and higher adjusted total costs ($66,107 ± 850 vs. $64,308 ± 1066) compared to the LFS group. Conclusions: Patients with prostate cancer and a high hospital frailty risk score exhibited significantly higher mortality rates, longer lengths of stay, and increased total adjusted costs. Frailty assessment plays a crucial role in predicting outcomes in patients with prostate cancer. Physicians can use frailty assessment to stratify patients based on risk and improve their ability to anticipate consequences.
Factors linked to patient rehabilitation disposition following surgical treatment of bone-related complications.
Authors: Corabi Jagger , Yan Vivian , Mallick Atrayee B. , Binder Adam F.
Published: June 2024

e23061

Background: Cancer in the skeletal system, whether primary or metastatic, can cause fractures or impending fractures needing stabilization. Patients with pathologic fractures or impending fractures needing prophylactic fixation have lower home discharge rates than non-malignant hip fracture cases, a recognized quality metric. We initiated a single-center retrospective study to identify modifiable risk factors for improving home discharge rates in this population. Methods: We reviewed orthopedic surgery patients at Thomas Jefferson University Hospital (TJUH) from July 2020 to April 2023. We assessed demographics, living situation, admission-to-surgery time, surgery-to-physical therapy time, in-hospital complications, pathological fracture site, and weight-bearing status. Patients were stratified into discharge groups: home, subacute rehabilitation, and acute rehabilitation. Differences in rehabilitation facility versus home discharges were analyzed using pairwise two-sample t-tests and Fisher exact tests. Results: In this study, 102 cancer patients underwent orthopedic intervention at TJUH. The cohort comprised 57 women (55.9%), 67 non-Hispanic white individuals (63.7%), with median age of 66.6 (52.4-80.8). Living alone increased the likelihood of discharge to an acute rehabilitation facility compared to home (13 vs. 5, p<.001). Lower median age correlated with home discharge compared to subacute and acute discharge (age 62.4 vs. 74.7, p<0.001; 62.4 vs. 66.9, p<0.05). Higher in-hospital complications, like sepsis, were associated with acute rehabilitation discharge versus home (24 vs. 17, p<.05). Conclusions: These results link living alone, older age, and in-hospital complications to rehabilitation facility discharge. No modifiable risk factors for home discharge were identified. This study reinforces the importance of caregiver support for patient outcomes and high-quality care. In the future, we intend to investigate if the in-hospital complications were avoidable and, thus, modifiable. A larger patient cohort may be required to reveal potential areas for improvement. [Table: see text]