bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravitreal chemotherapy (IVC) in retinoblastoma: A study of clinical variables and ocular preservation outcomes.
Authors: Epelman Sidnei , Mutran Thamires MJ , Teixeira Luiz Fernando , Gorender Ethel Fernandes , Carvalho Filho Neviçolino Pereira de
Published: June 2024

10059

Background: Retinoblastoma, a primary intraocular malignancy, poses unique challenges in preserving life and vision. This retrospective study aims to analyze the impact of IVC in a population of retinoblastoma patients. The primary objective to avoid external radiotherapy, a recognized risk factor for second neoplasms, particularly in germline retinoblastoma cases. Methods: We conducted an analysis of retinoblastoma patients from 2011 to 2024. Clinical variables, including sex, age, laterality, intraocular retinoblastoma staging, and therapies employed, were prospectively documented. Results: The study included 59 patients (37 male; 22 female). Thirty-three percent of patients had unilateral tumors and an average age of 28 months at diagnosis, and 67% had bilateral tumors with an average age of 15 months. Sixty-one eyes were treated and classified at diagnosis as follow: 6 (9.8%) in groups A and B, 10(18%) in group C, 37(64%) in group D, 6(11%) in group E, and 2(3%) without initial information. IVC was administered as part of a multimodal treatment approach. A total of 203 cycles of IVC were performed, averaging 3.4 cycles per patient. Melphalan was used in 39% of cycles, followed by the combination of melphalan and topotecan in 35%, and topotecan alone in 26%. Seven of 61 (11.5%) were enucleated. Three of 61 eyes (4.9%) received radiotherapy. Control of vitreous seeds and vision preservation were achieved in 57/61 eyes (93%). No grade 3 or 4 adverse events occurred. Conclusions: IVC emerges as a crucial component in the management of retinoblastoma, offering a viable alternative to external radiotherapy. The analysis highlights the importance of this approach in preserving ocular integrity, thereby avoiding enucleation and reducing the risk of second neoplasms, particularly in germline retinoblastoma patients.
Racial differences in background parenchymal enhancement, a novel marker of breast cancer.
Authors: Mahmoud Mattia , Ehsan Sarah , Mack Elizabeth , Edmonds Christine E , Kontos Despina , Chen Jinbo , Fayanju Oluwadamilola Motunrayo , McCarthy Anne Marie
Published: June 2024

10528

Background: Breast density is a risk factor for breast cancer that can guide eligibility for supplemental screening including MRI, but Black women are less likely to qualify for supplemental screening due to having less dense breasts on average despite higher rates of breast cancer mortality. Background parenchymal enhancement (BPE), the enhancement of fibroglandular breast tissue on contrast-enhanced MRI, is a novel biomarker that has been shown to be a superior breast cancer risk marker than breast density. Women with high BPE levels have up to a four-fold increased risk of breast cancer, even after adjusting for density, but no studies have examined BPE exclusively among Black women. Methods: We identified Black and white women ages 40-74 with no prior history of breast cancer who had a mammogram and subsequent MRI as part of a screening or diagnostic work-up from 2016-2022 at our institution. BPE was qualitatively defined according to BI-RADS (Breast Imaging Reporting and Data System), with four ordinal levels of increasing enhancement: minimal, mild, moderate, and marked. We conducted a cross-sectional study to perform a logistic regression with race as the exposure and moderate or marked BPE as the outcome, using minimal and mild BPE as the reference group, adjusted for age and BI-RADS density. Results: We included 1027 Black women and 4834 white women in our analysis. Fewer Black women had extremely dense breasts compared to white women (6% vs 13%, p= 0.04), however, there was a larger proportion of high BPE (moderate or marked) in Black women compared to white women (32% vs 28%, p = 0.03) (Table). There was an inverse association between age and BPE levels (p = 0.03), and a positive association between density and BPE levels regardless of race (p< 0.01) (not shown). Black women were 39% more likely to have high BPE levels (95% CI: 1.39 [1.19, 1.63]), adjusted for age and density. Conclusions: Black women have lower density but higher BPE than white women, suggesting that BPE may improve identification of breast cancer risk for Black women. Participants [Table: see text]
Health equity in multi-cancer early detection (MCEDs): A literature review and content analysis.
Authors: Negash Rosa , Doubeni Chyke , Bridges John F.P. , Crossnohere Norah L
Published: June 2024

10549

Background: Multi-cancer early detection tests (MCEDs) are an emerging screening technology to identify biomarkers of up to 50 different types of cancer using a single blood sample. While there is potential for MCEDs to advance health equity in cancer screening, considerations for how to do so are not established. We sought to identify emerging health equity themes related to MCEDs, and to explore where along the MCED evaluation process they have been considered. Methods: We conducted a targeted review of white and grey literature to identify references discussing health equity and MCEDs. We searched PubMed and Google Scholar from 2015-2024, using key search terms including “MCEDs,” “health equity,” and “diversity, equity and inclusion.” We used thematic analysis to identify health-equity related themes raised across included records. We then used content analysis to describe where these themes arose along the phases of cancer screening evaluation described by the CanTest Framework (product design, test performance, clinical feasibility, clinical effectiveness, and screening implementation). Results: We identified 22 records for inclusion, which varied in their content and depth when exploring health equity considerations for MCEDs. Thematic analysis of the records revealed five overarching health equity themes: access, acceptability, affordability, bias, and disparities. Acceptability, which included topics such as patient preference and measuring benefit/harms, and disparities, such as racial/ethnic differences in cancer deaths, were the most discussed themes (55% of records; Table). Bias, including provider discrimination, was the least discussed theme (32% of records). Content analysis revealed that health equity themes mostly arose across cancer screening evaluation phases of clinical feasibility, effectiveness, and implementation (82%, 73%, 64% of records respectively). No records explored health equity themes of acceptability, access, or bias in the product design phase (0%). Conclusions: Current literature considering health equity for MCEDs consistently address equity aspects related to clinical feasibility, clinical effectiveness, and implementation, but generally fails to consider health equity in early phase evaluation. Increasing consideration of health equity across all phases of the screening lifecycle is crucial if MCEDs are to advance health equity.[Table: see text]
Sugar-sweetened beverage intake and risk of oral cavity cancer: Results from 3 prospective US cohort studies.
Authors: Gomez Castillo Luis , Norouzi Armita , Cushing-Haugen Kara , Ferrandino Rocco , Rizvi Zain , Futran Neal D. , Marchiano Emily , Rodriguez Cristina P. , Harris Holly , Barber Brittany
Published: June 2024

10570

Background: Approximately 65% of adults in the US consume sugar-sweetened beverages (SSBs) daily, and consumption of SSBs substantially increased across successive birth cohorts in the US until 2000. Previous authors have identified an association between early-onset digestive tract cancers and SSBs. Recently, early-onset (<50 years) oral cavity squamous cell carcinoma has been observed in non-smoking, non-drinking individuals. The objective of this study was to investigate the association between SSBs and development of oral cavity cancer (OCC) in smokers, non-smokers, and those <50 years of age. Methods: We prospectively examined the association between SSB intake and OCC risk among 165,212 women in Nurses’ Health Study (NHS, 1986-2014) and Nurses’ Health Study II (NHSII, 1991-2015), and 45,790 men in the Health Professionals Follow-Up Study (HPFS, 1986-2014). All participants completed validated food frequency questionnaires (FFQs) every 4 years. Cox proportional hazards models adjusted for age, caloric intake, tobacco pack-years, alcohol intake, and BMI were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SSB intake and OCC incidence. Results: We identified 129 incident OCC cases in NHS/NHSII over 36 years of follow-up and 99 cases in HPFS over 30 years of follow-up for HPFS. The mean age at study baseline was 44.4 years for NHS/NHSII and 54.1 years for HPFS. Notably, in the multivariable adjusted model, increasing SSB intake was associated with a higher risk of OCC only among female participants in NHS/NHSII. Specifically, those in the highest quartile of SSB intake had a 229% increased risk of OCC compared to the lowest quartile (95% CI 1.29-4.07, ptrend=0.04). In non- or light-drinkers (<5g/day) in NHS/NHSII, SSBs was associated with OCC (HR=2.58, 95% 1.16-5.70, ptrend=0.10, N=81 cases). However, in non- or light-smokers (<5 pack-years), SSB intake was not associated with risk of OCC, though power was limited due to low case numbers (HR=1.56, 95% 0.66-3.68, ptrend=0.45, N=64). In contrast, no association of SSB intake with OCC risk was observed in the male HPFS cohort, overall (N=99) or among non-smokers (N=44). Early-onset OCC (<50 years) was limited to 9 patients, and thus a subset analysis could not be performed. Conclusions: Higher SSB intake was associated with a higher risk of developing OCC in women, but not men, after controlling for known risk factors. Reduction of SSB consumption may serve as a potential strategy to address the increase in OCC observed in recent years.
Prevalence of pathogenic genetic variants in patients with gastric cancer ascertained through multi-gene panel testing.
Authors: Gilad Ophir , Keel Emma , Russell Emily M. , Nielsen Young Sarah M. , Heald Brandie , Esplin Ed , Korn W. Michael , Roberts Maegan , Burke Carol A. , Kupfer Sonia S.
Published: June 2024

10578

Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. The role of pathogenic/likely pathogenic variants (PVs) in cancer predisposition genes is not well understood. We aimed to assess the prevalence of PVs in GC patients undergoing germline genetic testing (GGT) via multi-gene panel testing (MGPT) at a large commercial laboratory. Methods: Retrospective review of MGPT (>10 genes) in GC patients at a large commercial laboratory (Invitae Corp.) from March 2015 to July 2023 was performed. GC included diffuse type, intestinal type or unspecified type, as provided by ordering clinicians. Association of patient characteristics with positive GGT results was assessed with logistic regression with a significance threshold of p < 0.05. Results: 3,706 GC patients underwent GGT(Table). Overall, 495 (13.4%) patients were found to carry ≥1 PV, including 29 patients with 2 PVs and 3 patients with 3 PVs. GGT was negative in 1,890 (51.0%) patients, 1,199 (32.4%) had a variant of uncertain significance-only and 121 (3.3%) carried a single PV in a gene associated with autosomal recessive inheritance. PVs were identified in 38 genes; 77.7% (385/495) were in a gene previously associated with GC, primarily the homologous recombination repair genes ( BRCA1, BRCA2, PALB2and ATM, 34.9%), the Hereditary Diffuse Gastric Cancer genes ( CDH1and CTNNA1, 19.6%) and mismatch repair genes ( MLH1, MSH2, MSH6, PMS2and EPCAM, 17.4%). Males were more likely to carry a PV than females (OR 1.4, 95% CI 1.1-1.7) and having a personal history of another cancer increased the odds of carrying a PV (OR 1.3, 95% CI 1.0-1.7). Age, number of genes tested and histology were not significantly associated with PV. Conclusions: In this large study of GGT in GC patients, the prevalence of PVs in cancer associated genes was 13.4%, higher than previous estimates of 3-5%. PVs were predominantly in genes associated with GC. Male sex and history of other cancers were associated with a PV. Limitations include incomplete histologic data, varying panel size, and ascertainment bias as patients may have had additional personal/family history that prompted GGT. These results support consideration of GGT in all GC patients as prevalence of PVs is similar to other cancer types for which guidelines recommend universal genetic testing.[Table: see text]
Attitudes and engagement about cascade genetic testing in a population-based cohort of women diagnosed with cancer.
Authors: Katz Steven Jay , Ward Kevin C , Hamilton Ann S. , Abrahamse Paul , Hodan Rachel , Kurian Allison W. , Wallner Lauren P. , Hawley Sarah T.
Published: June 2024

10589

Background: Cascade testing in families with hereditary cancer syndromes is challenging because patients are responsible for engaging their relatives about test results and clinical support is limited. There are concerns that patient engagement with relatives may not be well matched to the clinical relevance of their test results, with particular concern about variants of uncertain significance (VUS). Methods: We selected patients from the Georgia California Genetic Linkage Initiative, which identified all patients diagnosed with cancer 2013-19 in the 2 states who linked to a germline genetic test. We surveyed 2100 women diagnosed with breast, ovarian or uterine cancer in 2018-19 in Georgia and California who reported "a pathogenic variant (PV) that increases the risk of cancer" on testing about 4 years after diagnosis. We also surveyed a comparable sample of 1300 women diagnosed during the same period who reported a VUS-only result. The expected response rate from the cohorts is 55% (N=1900). We present preliminary results on patient attitudes about cascade family testing and report of engagement with genetic counselors and relatives about test results. Results: The 2 cohorts were comparable in age (mean 54 vs 58 for VUS, p<.001) and education (college graduate or more 52% vs 53% for VUS p=.971). The Table shows that for patients who reported a PV, belief in the utility of testing in relatives (test results useful for family; wanted family members tested) was high. A substantial proportion reported that a genetic counselor encouraged them to talk to relatives and talked directly with relatives about testing. PV carriers informed most first-degree relatives about their test results. Patients who reported VUS only were less likely to endorse the utility of testing in relatives; less likely to report that a genetic counselor encouraged family engagement or engaged family directly about testing; and were less likely to have informed relatives about their test results. Conclusions: Compared to patients with VUS-only test results, women with PVs on germline genetic testing after diagnosis of cancer had more positive attitudes about the utility of testing of family members and greater engagement with clinicians and family members about test results. These findings suggest that engagement with family about genetic testing after cancer diagnosis matches the clinical relevance of the results. [Table: see text]
Germline sequence variation in Rwandan patients with breast and prostate cancer.
Authors: Manirakiza Achille Van Christ , Fadelu Temidayo , Baichoo Shakuntala , Uwineza Annette , Uwinkindi Francois , Dukundane Damas , Ngendahayo Edouard , Rubagumya Fidel , Muhawenimana Emmanuel , Nsabimana Nicaise , Besada Jeffrey , Nielsen Sarah M. , Bucknor Brianna A. , Koeller Diane R. , Andrews Caroline , Rebbeck Timothy
Published: June 2024

10591

Background: Clinically relevant cancer genetic data from Sub-Saharan Africa (SSA) are limited, despite the observation that cancers in this region are frequently diagnosed at an early age and follow an aggressive course. A prospective pilot study was undertaken to explore the feasibility of implementing germline genetic testing (GGT) and counseling in breast and prostate cancer patients in Rwanda. Methods: Consecutive female breast (FBC), male breast (MBC) and prostate (PC) cancer patients from hospitals in Rwanda underwent GGT. Demographic, disease, and treatment information were collected. A commercial 84-gene multi-cancer panel (Invitae Corp.) was used to identify pathogenic variants (PV) and variants of uncertain significance (VUS). Descriptive statistics were utilized. Results: 342 total patients underwent GGT: PV were observed in 32/175 (18.3%) FBC, 7/161 (4.3%) PC, and 1/6 (16.7%) MBC patients. PV were most frequently identified in BRCA2: FBC (n=14), MBC (n=1), PC (n=2). BRCA1 was almost common in FBC (n=11). The majority of PV in FBC cases were in established breast cancer susceptibility genes (94%), while 43% of PV in PC involved PC susceptibility genes. Notably, of 40 total PV identified, 35 (88%) were in DNA damage repair (DDR) genes. 224 patients (65%) had > 1 VUS in the absence of a PV finding, including 109 (68%) in PC and 115 (64%) in FBC/MBC combined. Recurrent PV were observed in BRCA1, BRCA2, or ATM in apparently unrelated FBC cases. Conclusions: The high proportion of PV, observed in these Rwandan breast and prostate cancer cases, particularly in DDR genes, suggest that GGT should be more routinely implemented into cancer care and prevention strategies in this population. More widespread GGT may also help to resolve the high VUS rates. The recurrent variants identified warrant further investigation into founder effects. [Table: see text]
Timing of genetic testing referral and genetic testing results in patients with multiple primary cancers.
Authors: Hodan Rachel , Ritter Victor , Han Summer S. , Narayan Shilpa , Satoyoshi Mina , Kurian Allison W.
Published: June 2024

10592

Background: An individual diagnosed with a metachronous or synchronous cancer that arises independently, not due to recurrence or metastasis, has multiple primary cancers (MPC). Practice guidelines recommend germline genetic testing based on specific combinations of primary cancers and ages of diagnoses but do not recommend testing for all patients with MPC. In prior work (PubMed ID 37276540), we found that patients with breast cancer are more likely to receive testing than patients with other primary cancer types. Here, we evaluated whether a first breast cancer was more likely than another first cancer type to prompt testing referral. Methods: Using Oncoshare, a breast cancer research database that integrates data from electronic medical records and the California Cancer Registry, we identified female patients with MPC diagnosed between January 2000 and June 2023 with breast cancer as either the first or second cancer and seen at Stanford University. We analyzed testing rates after first vs. second cancer diagnosis and the yield of pathogenic variants (PV). We evaluated the association between the receipt of genetic testing and the timing of breast cancer (1st or 2nd), using both univariate and multivariable logistic regression that adjusted for age at first diagnosis, race/ethnicity, and time between the first and second diagnoses. Results: 1,069 patients met the study eligibility; 75% were non-Hispanic White, and 73% had breast as the first cancer. 342 (32%) patients had testing, and 113 (33%) had at least one PV. Most patients had testing after the first cancer (44%, n=150) or after the second cancer (48%, n=165) (Table). Those with breast cancer as their first primary tended to have a higher testing rate, (OR 1.62, 95% CI 0.9-3.0), however, the statistical significance of this association was attenuated in the multivariable model with more parameters (P=0.11), possibly due to small sample size. Overall PV yield (33%) was high, consistent with a tertiary referral center. Conclusions: In this academic clinic-based sample of patients with MPC, we observed a higher testing rate when breast vs. another cancer was the first primary although it did not reach statistical significance. Additional research is needed to validate this finding in a larger cohort and determine whether similar referral patterns are observed in community practice, where most U.S. patients receive cancer care. [Table: see text]
Universal germline testing for cancer susceptibility and actionable noncancer disorders among 19,842 patients: Initial findings from the City of Hope INSPIRE study.
Authors: Gray Stacy W. , Solomon Ilana , Hampel Heather , Garcia Michael , Shaktah Lawrence , Dreike Sandra , Idos Gregory , Gima Lauren , Lindsey Sidney S. , Luong Marilan , McDonnell Kevin , Nehoray Bita , Park Wai , Shehayeb Susan , Sobotka Elise , Xiao Yi , Zukin Elyssa , Bonner Joseph D. , Hamilton Stanley R. , Gruber Stephen B.
Published: June 2024

10594

Background: Germline testing can be essential for risk stratification and therapeutic decision making. However, guideline-based testing misses ~50% of people with inherited cancer risk. To address this gap, we launched the INSPIRE study, offering universal germline testing (31 non-cancer and 154 cancer genes) to consented patients affected and unaffected with cancer. Methos: In 2020, we initiated a scalable in person/remote consent model without formal pre-test counseling. Consenting patients opted-in for one, both, or neither germline test. Research staff placed orders. Results were reviewed by a genetic counselor. Pathogenic/likely pathogenic (P/LP) and increased risk allele (IRA) results were disclosed by phone and scheduled for a genetic consult. Variant of uncertain significance (VUS)/negative results were disclosed by letter with a genetic consult available on request. Descriptive statistics and chi-squared tests evaluated a priori hypotheses regarding potential factors impacting genetic testing uptake and actionability. Results: We approached 26,920 patients: 22,115 (82%) enrolled, 1,830 (7%) declined, 2,975 (11%) deferred a decision. Consented patients opted for testing for germline cancer (21,871/ 99%), non-cancer (21,731/98%), or neither (160/0.7%). We have returned results to 19,842 patients: mean age 62, 69% female; 72% white, 14% Asian, 5% Black, 9% other; 24% Hispanic. Most patients (15,578) had cancer, 13% with multiple primaries. Among the 19,842 patients, 4,456 (23%) had at least one P/LP/IRA variant; 3,971 (20%) in a cancer risk gene and 589 (3%) in a non-cancer gene. Variant proportion by category was 1,466 (30%) high-penetrance, 847 (18%) moderate-penetrance, 1,127 (23%) low-penetrance, 1,282 (28%) recessive, and 34 (0.7%) preliminary evidence. Penetrance prevalence differed by sex: high penetrance variants were more common in females (33% vs. 27%; p=<0.001) and moderate penetrance variants were more common in males (21% vs. 17%; p=0.003). 16,883 (85%) individuals carry at least one VUS. Conclusions: A scalable model to increase germline genetic testing among unselected cancer and unaffected patients across >20 sites was highly feasible. A significant proportion of patients had actionable findings in cancer and non-cancer genes. Next steps include analyses to establish variant prevalence across groups, a longitudinal assessment of psychological outcomes and an evaluation of the impact of result disclosure on cost, patient care, and outcomes.
A targeted panel of actionable high-risk hereditary cancer predisposition genes to identify patients with pathogenic/likely pathogenic variants (PVs) irrespective of meeting established NCCN testing criteria.
Authors: Lee Sarah S. , Zhang Jingwen , Mackall Mia , Bristow Sara L. , Malhotra Meenakshi , ElNaggar Adam , Souter Vivienne , Liu Minetta C. , Pothuri Bhavana
Published: June 2024

10596

Background: Current germline cancer testing guidelines are limited to patients who meet specific personal and family cancer history (PH, FH) criteria. Our objective was to determine if differences in PV rates exist based on meeting National Comprehensive Cancer Network (NCCN) testing criteria in patients who underwent testing for known actionable genes. Methods: 29 genes with actionable NCCN management guidelines were evaluated. Consecutive patients (N=195,615) aged 18 to 100 years had hereditary cancer testing at a commercial laboratory at the ordering clinician’s discretion that included at least the 29 genes between June 2020 and August 2023. Per clinician-reported patient features (e.g. FH, PH, age), patients were categorized as meeting or not meeting current NCCN testing criteria for breast/ovarian/pancreatic (BOP v2.2024), and colorectal cancer (v1.2023). PV rates were calculated for all genes associated with breast, endometrial, ovarian, prostate, pancreatic, and colorectal cancer risk. Results: PVs were reported in 6634/105,194 (6.3%) patients that met the testing criteria and 5134/90,421 (5.7%) that did not. Of patients with a PV, 5134/11,768 (43.6%) did not meet NCCN testing criteria. When comparing patients with PVs based on NCCN testing criteria, patients were similar in age (median [Q1, Q3], 43.6 [35.0, 56.1] v 42.5 [34.7, 56.6] years) and sex (female 91.5% v 91.3%). While PH and FH were comparable, a PH of cancer (31.5% v 36.1%, OR=0.81, 95% CI 0.75-0.88, p<0.001) and/or a FH of cancer (83.9% v 97.1%, OR=0.16, 95% CI [0.13-0.18], p<0.001) were slightly lower in patients who did not meet criteria compared to those who met testing criteria. On evaluating results in genes associated with individual cancer types, similar PV rates between the groups were observed (Table). Among all patients with PVs, the most common genes were CHEK2, BRCA1, BRCA2, and ATM. Most patients had only 1 PV reported (met: 96.5%, not met: 97.5%). Conclusions: In this cohort of patients who underwent germline testing, approximately 40% of patients with PVs in this study did not meet existing NCCN testing criteria. PV rates were similar between patients that met criteria and those that did not. Broadening existing testing criteria may reduce the number of patients who would otherwise be missed, thereby allowing for treatment decision-making and cascade testing of family members. [Table: see text]
NSQIP audit of enhanced recovery after surgery protocols for radical cystectomy.
Authors: Pfail John , Passarelli Rachel , Kaldany Alain , Chua Kevin J. , Lichtbroun Benjamin , Srivastava Arnav , Golombos David , Jang Thomas L , Packiam Vignesh T. , Ghodoussipour Saum
Published: June 2024

11009

Background: Utilization of enhanced recovery after surgery (ERAS) protocols for radical cystectomy (RC) has been associated with improved postoperative recovery and shorter hospital stays. The multiple components within ERAS leads itself to heterogenous implementation across different institutions. We aimed to assess the impact of increasing compliance to ERAS components on postoperative outcomes in patients who underwent RC. Methods: The National Surgical Quality Improvement Program database included 3,708 patients who underwent RC from 2019 to 2021. ERAS components of interest included regional anesthesia block, no bowel prep, no prolonged NGT or NPO status, VTE prophylaxis with mechanical and pharmacologic means, and antibiotic duration < 24 hours. Baseline characteristics and complications were stratified by number of ERAS components utilized (≤ 3, 4, or 5). Statistical endpoints included thirty-day complications, length of stay (LOS), and readmissions. Optimal RC outcome was defined as absence of any postoperative complication, reoperation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable analyses with Bonferroni correction were performed to assess the association between ERAS compliance and outcomes. Results: Of the 3,708 patients who underwent RC with ERAS components utilized, 1,506 (41%) received ≤ 3 interventions, 1454 (39%) received 4, and 748 (20%) received 5. Baseline characteristics were relatively similar across the three groups. On multivariable analysis adjusted for multiple hypothesis testing, when compared to patients who received ≤ 3 interventions, patients who received 4 and 5 interventions had lower rates of any complication (OR 0.71; 99% CI [0.58 - 0.88], OR 0.74 [0.57 - 0.95], respectively), and shorter LOS (β -1.32 [-1.69, -0.95], β -1.74 [-2.19, -1.28], respectively). Moreover, patients with increased ERAS compliance experienced increased odds of an optimal outcome (OR 1.68 [1.38 – 2.05], OR 1.97 [1.55 – 2.51], respectively). Conclusions: Greater adherence to ERAS protocol interventions yielded superior post-operative outcomes for patients who underwent RC. This large-scale analysis supports that ERAS protocols are beneficial in a dose-dependent fashion and should be utilized. [Table: see text]
5-year multicenter analysis of clinical trial participation and total cost of care for older adults with cancer.
Authors: Subbiah Ishwaria M. , Indurlal Puneeth , Alam Naiyar , Ives Hope , Staggs Stuart George , Wilfong Lalan S.
Published: June 2024

11013

Background: Clinical trial access particularly for older adults aged 65 years and above with cancer is impacted by multilevel barriers, including cost concerns to payers in the usual models of cancer care delivery. Alternative models recently studied include the Centers for Medicare and Medicaid Innovation’s Oncology Care Model (OCM), a value-based care pilot to enhance quality & reduce costs. Here, we investigated the association between clinical trial participation (CTP) and the total cost of care (TCOC) within this non-traditional model. Methods: We identified prospective longitudinal observational cohort of patients cared for in 11 states within 323 clinics in 14 multi-site community practices participating in OCM, in The US Oncology Network and extracted data (episode claims, medical records, episodes) from OCM performance periods (PP) 3-11 between 7/1/17 and 6/30/22. Propensity score matching by PP, age, gender, date of death, cancer type identified the analysis cohort of matched episodes, then stratified by trial participation (CTP vs usual care) to compare TCOC and drug expenditures. Results: Over 5 years, 121,717 unique patients (94% of whom were aged 65y+) received 282,604 episodes of cancer care in the community, most common cancers being breast, lung, multiple myeloma. Propensity score matching identified 13,260 matched episodes (6630 usual care, 6630 CTP). The actual expenditure differed by $2,341 per episode between CTP & usual care (CTP $43,890 vs usual care $41,548; p < 0.0001), while trial participation had significant savings against the OCM CTP benchmark ($4816 saved per CTP episode), compared to usual care vs its benchmark ($826 saved per usual care episode, p < 0.0001). Drug costs per episode did not differ between the two groups (CTP $29,516 vs usual care $30,553; p 0.54). Further breakdown shows that drug spending on anticancer agents (CTP $28,008 vs usual care $29,139) and other drugs including supportive care meds (CTP $1,511 vs usual care $1,414) did not differ significantly. Conclusions: Clinical trial participation saw relative cost savings against the benchmark compared to usual care, owing largely to the higher benchmark prices for CTP episodes in OCM’s risk-adjusted price prediction model, rather than an absolute cost savings to payers. Drug expenditures remain the largest contributor to total cost of care in this alternative model. The contributors to both drug expenditures as well as the absence of absolute cost savings between the two cohorts represent key areas for further investigation. CMMI Disclaimer: The statements contained in this document are solely those of the authors and do not necessarily reflect the views or policies of CMS. The authors assume responsibility for the accuracy and completeness of the information contained in this document.
Evaluation of the study of control arms in randomized clinical trials of cancer.
Authors: Jain Sandeep Kumar , Zauderer Marjorie Glass , Sethi Tarsheen , Schoen Martin W. , Rubinstein Sam , Nguyen Ryan Huu-Tuan , Nagpal Seema , Mohan Sanjay , Madireddy Sathwik , Lythgoe Mark , Liang Wayne , Kulkarni Amit , Kothari Shalin , Hilal Talal , Hadfield Matthew James , Goyal Gaurav , Ganta Teja , Dholaria Bhagirathbhai R. , Brown Alaina J. , Warner Jeremy Lyle
Published: June 2024

11023

Background: Randomized clinical trials (RCTs) in cancer typically compare experimental to control arm regimens. The choice of an appropriate control (ctrl) arm can have a major impact on the expected success of an RCT. The frequency with which cancer RCTs use control arms based on established dosing and scheduling protocols has not been described. Methods: The HemOnc knowledgebase (KB) was used to identify systemic anti-cancer therapy (SACT) regimen variants, defined as regimens with identical components that differ in dosing, scheduling, and/or route. Non-cancer, nonrandomized, and non-SACT studies were excluded. Study publication year was used to define standard variants as those evaluated in the experimental arm of a positive phase 3 RCT >1 year prior to publication as a control arm, regardless of cancer type or context of treatment. Study-variant dyads were evaluated to determine whether the variant was standard. Success rates of RCTs with standard vs non-standard control arms were evaluated with Fisher’s exact test. Results: 5221 studies were associated with ≥1 named variant in the HemOnc KB, as of 2024-02-06. After exclusions, there were 3511 study-variant dyads (2386 studies; 1714 variants). The 9 most common regimens are shown in the Table. The median (IQR) number of variants per regimen was 2 (1-3); carboplatin & paclitaxel (CP) had the most variants (n=33). Across all control arm study-variant dyads, 2228/3492 (64%) utilized non-standard variants. For example, 60/97 studies (62%) of docetaxel as control used the 75 mg/m2 q3wk variant after it was established in 2000, whereas n=27 others used 19 non-standard variants. Trials that used a standard control arm had a numerically higher success rate, 45% vs 42% (OR 1.10, 95% CI 0.92-1.32). Conclusions: Non-standard regimen variants are frequently used in cancer RCTs. Reasons for this could include toxicity, patient convenience, or emerging data from smaller studies that establish comparable efficacy or improved toxicity to standard variants. However, the a priori efficacy of non-standard control arms is less rigorously established, and trials with standard control arms might be more successful. Future directions include quantifying the granular differences between standard and non-standard variants and investigating whether certain types of non-standard variation (e.g. fewer cycles, lower doses) associate with trial success rates. [Table: see text]
Examining the financial landscape of cancer: An analysis of debt and bankruptcy among patients in Massachusetts (2010-2019).
Authors: Uppal Nishant , Gomez-Mayorga Jorge , Fleishman Aaron , O’Donoghue Ashley L. , Bogdanovski Anastasia , Esselen Katharine , James Benjamin
Published: June 2024

11032

Background: Financial toxicity is commonly reported by patients following a cancer diagnosis. Prior patient surveys indicate that up to one-third of cancer patients incur medical debt, of which 55% carry balances exceeding $10,000. In addition to debt and bankruptcy, credit scores are an important indicator of socioeconomic well-being following cancer diagnosis, because they affect housing stability, transportation access, and may even be predictive of health. Limited studies quantify incurred debt, bankruptcy rates, or credit scores following a cancer diagnosis compared with patients without a cancer diagnosis. Methods: Individuals with a cancer diagnosis in Massachusetts from 2010 to 2019 were identified through the Massachusetts Cancer Registry, and patient-level records on debt, bankruptcy, and other measures of financial well-being were linked using data from a major United States credit bureau. Changes in medical debt, credit score and bankruptcy filings were evaluated over time and compared with a random sampling of individuals residing in Massachusetts over the same time period that did not have a cancer diagnosis and were matched based on demographic factors. Results: 99,175 individuals with cancer and 188,875 individuals without cancer were identified, and average annual total debt balances were $758 and $669, respectively, throughout the study period. The highest total debt balances were observed among individuals with thyroid cancer ($913). Average annual medical collection balances were $45 for individuals without cancer and $52 among those with cancer with the highest balances among those with liver cancer ($66). Across the study period, the average annual bankruptcy incidence rate per 100 persons was 7.15 for those without cancer and 6.22 among those with cancer, with the highest incidence rates among those with thyroid cancer (7.34). Although there was a gradual increase in credit score in the control population, survivors of bladder, liver, ovarian, colorectal and lung cancers experienced a decline in credit scores. Conclusions: High rates of financial toxicity among individuals with cancer suggest that widespread healthcare and consumer finance reforms have not yet fully alleviated medical debt and bankruptcy in Massachusetts. Further research is needed to understand drivers of financial burden over time among those with cancer.
Development and validation of point-of-care mobile solution to guide the diagnosis of malnutrition: A multicenter, prospective cohort study.
Authors: Zhou Xueyan , Lin Nan , Ma Xuelei
Published: June 2024

11042

Background: Malnutrition has negative effects on patients with chronic diseases, leading to reduced treatment tolerance, increased risk of clinical complications, and even death. This research was aimed to develop a point-of-care program based on facial features to screen malnourished inpatient patients. Methods: In this prospective, multicenter, cohort study, we retrieved facial photograph and malnutrition screening scales from 4 different hospitals. We utilized a variety of machine learning models to explore whether the ocular area could serve as an enhanced region for facial recognition nutrition. Last, we utilized a facial area segmentation and weighted approach to retain the information of full-face features using a BP neural network and validated using Delong-test, IDI-test, and NRI-test. Overall, 619 inpatients’ facial photographs and their corresponding nutrition screening questionnaires were used to train, validate and test the machine learning model. Results: The Pearson correlation analysis showed a significant correlation (p<0.05) between the two questionnaires in all groups. The average AUC obtained from the five-fold cross-validation set was 0.886 (CI 0.843-0.930), 0.834 (CI 0.764-0.904), and 0.927 (CI 0.899-0.955) for the Cancer Inpatient Group, Other Inpatient Group, and All Inpatient Group, respectively, with the corresponding AUC obtained from the external validation set being 0.860 (CI 0.817-0.904), 0.843 (CI 0.796-0.889), and 0.887 (CI 0.829-0.944). Conclusions: The facial photograph-based point of-care mobile solution can screen malnutrition with good accuracy, showing its potential for screening malnutrition in inpatients in the hospital in different types of diseases.
Association of cancer survivors’ experience of care with financial toxicity: Results from a national survey.
Authors: Halpern Michael T. , Knowles Reegan Kate , Thamm Carla , Chan Raymond J
Published: June 2024

11099

Background: Financial Toxicity (FT), negative economic impacts resulting from cancer or cancer treatment, can adversely affect quality of life, treatment adherence, and clinical outcomes. Patient experience of care (EoC) captures information from patient’s perspectives on interactions with healthcare providers and systems and receipt of medical care services. While EoC is used to evaluate health care system and provider quality, the impacts of EoC on FT are unknown. Methods: To examine associations of EoC and FT, we used data from the from the 2016-2017 Experience of Cancer Survivorship Supplement of the Medical Expenditure Panel Survey (MEPS), the most recent years available of this national U.S. household survey. EoC was assessed using patient-reported frequencies (rated “never/sometimes”, “usually”, or “always”) of their health professionals explaining things in a way that was easy to understand; listening carefully; showing respect; and spending enough time with the patient in the past 12 months. FT was based on 9 MEPS items and classified as material FT (borrowing money, making financial sacrifices due to cancer), psychologic FT (worry about paying medical bills or financial stability), and behavioral FT (delaying/forgoing cancer care due to costs). Analyses were performed using multivariable logistic regressions controlling for patient sociodemographic and clinical characteristics and weighted to produce nationally representative estimates and address survey non-response. Results: Data included 1068 individuals diagnosed with cancer at age 18 or older; 30% reported material FT, 35% psychologic FT, and 27% behavioral FT. Examining EoC, 64% of respondents indicated their health professionals always explained things; 60% that they always listened; 66% that they always showed respect; and 57% that they always spent enough time with the patient. In multivariable regressions, the odds of psychologic FT were significantly (p<0.05) lower among patients reporting their health professionals always (vs. never/sometimes) listened (odds ratio [OR] 0.37, 95% CI 0.19-0.70), showed respect (OR 0.36, 95% CI 0.16-0.81), and spent enough time with the patient (OR 0.47, 95% CI 0.26-0.86). Significant associations with EoC were also found with individual psychologic FT questions from the MEPS on worry about paying bills, financial stability, and keeping job/income. Conclusions: Worry/anxiety regarding costs can be a major factor affecting individuals with cancer. Improving patient-provider interactions to enhance patient EoC may help reduce this aspect of FT.
Viral hepatitis screening in patients with early breast cancer receiving cancer therapy: A quality improvement initiative.
Authors: Klein Katherine , Hwang Jessica Park , Valero Vicente , Ramirez David Luis , Kaushik Jaime
Published: June 2024

11125

Background: ASCO guidelines recommend screening all patients for hepatitis B virus (HBV) before initiation of cancer therapy. Comprehensive screening for HBV includes measuring HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), and antibody to HBV surface antigen (anti-HBs). ASCO also recommends hepatitis C virus (HCV) screening in patients with cancer. Cancer patients receiving cancer therapy represent a vulnerable population and reactivation of undetected hepatitis virus can lead to devastating consequences such as liver failure and death. At MD Anderson Cancer Center, rates of hepatitis screening for all cancer patients has been historically low. For example, rates are around 29% for HBV screening in patients receiving cancer therapy in 2019-2021. The aim of this quality improvement study is to increase rates of HBV and HCV screening in early breast cancer patients in the Breast Medical Oncology clinic at MD Anderson before undergoing cancer therapy to at least 50%. Methods: Quality improvement measures were implemented by 1) creation of an order panel in the electronic medical record (EMR) which contains all tests needed for comprehensive HBV and HCV screening (HBsAg, anti-HBc, HBsAb, and anti-HCV), and 2) an educational session to providers in the Breast Medical Oncology clinics. Data was collected for patients seen at MD Anderson initiating cancer therapy (start of cycle 1) between April 1, 2023 until September 30th, 2023. Inclusion criteria were early breast cancer patients (Stage I-III) and receiving chemotherapy at MD Anderson. Exclusion criteria were Stage IV disease, or those receiving chemotherapy at an outside institution. Results: A total of 340 patients were screened, and 219 were determined to meet inclusion criteria for data extraction. In total, 105 patients (48%) received comprehensive HBV screening, with 137 (63%) receiving at least one HBV test. A total of 122 (56%) patients were screened for HCV. Combining data for both HBV and HCV, 88 (40%) received both comprehensive HBV and HCV screening (HBsAg, anti-HBc, anti-HBs, anti-HCV). A majority of patients (91% for HBV and 93% for HCV) were screened prior to cycle 1 of cancer therapy. The EMR order panel was utilized in 51 (23%) of patients. Anti-HBc was positive in 8 of those tested, and HBsAg was positive in 1 patient. No patients tested positive for HCV. Conclusions: Screening rates for HBV and HCV individually were near or exceeded our goal, however rates of combined HBV and HCV screening were lower. Going forward, additional education to providers as well as increased awareness of the available order panel will be needed to ensure we are comprehensively screening for both HBV and HCV in our patients. [Table: see text]
Commercial health plan spending on oncology drugs approved via the accelerated approval pathway and later withdrawn from the market.
Authors: Patel Tejas , Curran Eamonn , Hellems Sarah S
Published: June 2024

11134

Background: The U.S. Food and Drug Administration (FDA) introduced the Accelerated Approval Program in 1992 to expedite the approval of drugs that can be used to treat certain conditions and fill an unmet medical need. Clinical trials conducted to achieve accelerated approval status often use surrogate outcomes as primary endpoints to reduce the time it takes to get FDA approval. Drug manufacturers must conduct further research to verify and report the projected clinical benefit and safety. The FDA may issue traditional approval to previously accelerated approved drug or may request the manufacturer to withdraw a drug from the market based on the clinical benefit and/or safety demonstrated in the confirmatory trial(s). We report members impacted, total drug claims, and total drug cost incurred by a commercial health plan associated with the coverage of oncology drugs approved by the FDA and later withdrawn from the market between 2020 to 2023. Methods: Fifteen unique indications associated with oncology drugs that received accelerated approval and later withdrawn by the FDA were identified between 2020 to 2023. A cohort of patients enrolled in commercial health plan was further identified using the ICD-10 code related to the drug indication being withdrawn. To calculate total paid amount for drugs, de-identified administrative claims data submitted on behalf of this cohort were sorted and summed in this time period using either J-code for drugs covered under medical benefits or national drug code (NDC) for drugs covered under pharmacy benefits. Results: Between 2020 to 2023, 8 oncology drugs were withdrawn because of later failing to demonstrate clinical benefit in the confirmatory trials, 2 drugs were withdrawn due to safety concerns, and 5 drugs were withdrawn due to drug manufacturer unable to complete a confirmatory trial. In this population, we identified 18,430 unique members with 103,743 administrative claims. The total paid amount was $1,392,553,995 in this time period. The average drug cost per administrative claim was $13,423 and the average drug cost per member was $75,559. Conclusions: Drug costs established by manufacturers are not differentiated based on the approval status - accelerated or regular. While drugs approved via accelerated approval pathway may provide benefit to certain patient population, the cost associated with accelerated approved drugs needs more attention. Indication-specific pricing model may help alleviate the cost burden associated with drugs approved via accelerated approval pathway. [Table: see text]