tbuckley/cabot-search huggingface dataset:
Inpatient outcomes of pathological fractures in metastatic prostate cancer.
Authors: Kriti Ahuja, Prasanth Lingamaneni, hisham laswi, Dennis Danso Kumi, Navika Chhabra, Omnia Darweesh, Kunnal Batra
Journal: Journal of Clinical Oncology (2021)

e17007 Background: Bone is a frequent site of metastasis in prostate cancer and is involved in 88% of patients with metastatic prostate cancer. Metastasis to bone increases the risk of pathological fractures, which are associated with increased morbidity and mortality. We performed a retrospective analysis on inpatient outcomes of pathological fractures in prostate cancer metastatic to bone in comparison to men with osteoporotic fractures. We also examined the disposition of these patients. Methods: We queried the Nationwide Inpatient Sample between 2016 and 2018 to retrospectively identify adult males with osteoporotic fractures and those with pathological fractures secondary to metastatic prostate cancer. We used T-test and chi-square test to compare means of continuous variables and compare proportions of categorical variables respectively. Multivariate analysis of predictors of mortality, length of stay, hospitalization costs and disposition in this group were performed. Results: A total of 22,800 fractures, combining osteoporotic fractures and pathological fractures due to metastatic prostate cancer were identified, of which the latter accounted for 13.6%. Patients with pathological fractures secondary to metastatic prostate cancer were younger (mean age 73.5 vs 77.5 years, p &lt; 0.0001) and more likely to be black (16.4% vs 4.6%, p &lt; 0.0001) or Hispanic (8.4% vs 5.1%, p &lt; 0.0001). Adjusting for demographic variables and comorbidity burden, pathological fractures in patients with prostate cancer metastasis to the bone were not associated with a significant increase in mortality (aOR 1.46, 95% CI 0.82-2.60, p = 0.20) or length of hospital stay. However, they did have higher hospitalization costs by $2,610 per admission (p = 0.01). Patients with pathological fractures secondary to prostate cancer are less likely to be discharged to a nursing facility (aOR 0.50, 95% CI 0.40-0.62, p &lt; 0.001) and are more likely to be transitioned to home health care (aOR 1.49, 95% CI 1.20-1.84, p &lt; 0.001). Conclusions: Pathological fractures secondary to prostate cancer are less frequent than osteoporotic fractures in men and are not independent predictors of mortality or length of stay. This is in keeping with the relatively indolent course of prostate cancer. However, there is an increased cost of hospital stay associated with pathological fractures in metastatic prostate cancer. Interestingly, these patients are more likely to be discharged with home health care and are less likely to go to a nursing facility, making disposition a crucial aspect in the care of these patients.
Family history of breast and/or ovarian cancer (FHBOC) as an independent prognostic factor in triple negative breast cancer overall survival.
Authors: Patricia Rioja, Rossana Ruiz, Zaida Morante, Raul Mantilla, Gabriel Antonio De la Cruz Ku, Maria Lujan-Peche, Jose Manuel Cotrina, Hugo Fuentes, Silvia P. Neciosup, Henry Leonidas Gomez
Journal: Journal of Clinical Oncology (2021)

e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1 st , 2 nd and/or 3 rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1 st , 2 nd , and 3 rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.
Adverse Effects of Medications on Micronutrient Status: From Evidence to Guidelines
Authors: Michael S. Daniels, Brian I. Park, Diane L. McKay
Journal: Annual Review of Nutrition (2021)

Recent dietary reference intake workshops focusing on nutrient requirements in chronic disease populations have called attention to the potential adverse effects of chronic medication use on micronutrient status. Although this topic is mostly ill defined in the literature, several noteworthy drug-nutrient interactions (DNIs) are of clinical and public health significance. The purpose of this narrative review is to showcase classic examples of DNIs and their impact on micronutrient status, including those related to antidiabetic, anticoagulant, antihypertensive, antirheumatic, and gastric acid-suppressing medications. Purported DNIs related to other drug families, while relevant and worthy of discussion, are not included. Unlike previous publications, this review is primarily focused on DNIs that have sufficient evidence supporting their inclusion in US Food and Drug Administration labeling materials and/or professional guidelines. While the evidence is compelling, more high-quality research is needed to establish clear and quantitative relationships between chronic medication use and micronutrient status.
Scalp cooling to reduce alopecia as a barrier to chemotherapy.
Authors: Isabel M. Pupo Wiss, Dina Hagigeorges, Chloe J. Walker, Kelly E. Flanagan, James T. James, Molly C. Geary, Mary Fay, Maryanne M Senna, Steven J. Isakoff
Journal: Journal of Clinical Oncology (2021)

e12537 Background: Chemotherapy induced alopecia (CIA) is one of the most distressing adverse events reported by patients undergoing chemotherapy, yet there is limited data addressing the impact of CIA on treatment acceptance. Scalp cooling (SC) has been shown to decrease CIA. Here we report our assessment of CIA as a barrier to chemotherapy and the efficacy of SC using pre- and post-treatment surveys of patient reported outcomes. Methods: Patients who received alopecia-inducing chemotherapy and utilized SC between November 2018 and September 2020 at our institution were enrolled in a prospective IRB approved registry. Surveys including the Chemotherapy Induced Alopecia Distress Scale (CADS) were administered before and within two weeks after treatment. Using the CADS survey, patients were asked about their hesitation to receive chemotherapy and the burden they feel about alopecia as a side effect of chemotherapy. Results: Of 90 patients who completed the first or last treatment survey, the most common treatment regimens were docetaxel/cyclophosphamide (TC), docetaxel/carboplatin/trastuzumab/ pertuzumab (TCHP), and paclitaxel/trastuzumab (TH). The most common disease type was breast cancer (92.2%) and all participants were females. Of 74 SC patients who completed the pre-treatment survey, the median age was 50.5 (range 26-75) and included 65 (87.8%) Caucasian, 4 (5.4%) Black, and 3 (4.0%) Asian patients. 89.2% used Paxman SC and 10.8% used Penguin SC. Of those who completed the CADS survey prior to treatment, 8 (10.8%) reported ‘quite a bit’ to ‘very high’ hesitation, and 34 (46.0%) reported feeling that alopecia was either ‘quite’ or ‘very much’ a burden of chemotherapy. All 40 SC patients (median age 53.5, range 31-76) who completed the post-treatment survey were Caucasian and used Paxman SC. Self-reported efficacy of SC in these 40 patients was less than 10% hair loss in 10 (25.0%), 11-25% hair loss in 7 (17.5%), 26-50% hair loss in10 (25.0%), 51-75% hair loss in 9 (22.5%), and 76-100% hair loss in 4 (10%). Overall, 27 (67.5%) patients reported SC limited alopecia ‘a lot’ to ‘perfectly’. Conclusions: In our study, alopecia was identified as a notable burden to nearly half our SC patients and 10.8% hesitated when making their decision to receive chemotherapy. After using SC during treatment, 67.5% of patients reported less than 50% hair loss, and 67.5% reported that SC reduced alopecia ‘a lot’ or ‘perfectly’. Our study highlights the significance of alopecia as a chemotherapy burden and potential barrier to accepting treatment, and suggests SC may be efficacious in decreasing CIA, which may allow patients to feel less hesitation towards chemotherapy.
Epithelial ovarian cancer survival by race/ethnicity in an equal-access healthcare population.
Authors: Zhaohui Liao Arter, Daniel Desmond, Jeffrey L. Berenberg, Melissa A. Merritt
Journal: Journal of Clinical Oncology (2021)

e18525 Background: Previous studies in the general population have observed that compared with Non-Hispanic White (NHW) women, Pacific Islander (PI) and Non-Hispanic Black (NHB) women have higher age-adjusted mortality rates from epithelial ovarian cancer (EOC), while Asian Americans (AS) have lower mortality. It is unknown whether these patterns reflect biological differences, environmental exposure or perhaps access to care. Our objective was to investigate whether self-reported race/ethnicity is associated with differences in EOC survival in a Military population where patients have equal access to healthcare. Methods: The study population included women diagnosed with EOC (ovarian, fallopian tube and primary peritoneal cancers) among US Department of Defense beneficiaries reported in the Automated Central Tumor Registry Database (year of diagnosis range: 2001-18). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models following participants from their date of diagnosis until last contact or censoring, whichever occurred first. Multivariable models were adjusted for covariates selected a priori because of their known influence on risk of EOC death; age at diagnosis (continuous), histology, stage and receipt of the first course of chemotherapy treatment. We adjusted for year of diagnosis (continuous) to account for possible changes in treatment over time. Results: The study population included 1151 patients diagnosed with EOC: 796 NHW, 111 NHB, 130 AS, 49 PI and 65 Hispanic (HS). All EOC patients had complete information on age at diagnosis, stage and chemotherapy treatment. During a median (interquartile range) follow-up of 3.5 years (1.8-6.7), 702 EOC patients (61%) died of all causes. When comparing crude EOC patient characteristics by racial/ethnic group, NHW had the highest frequency of EOC leading to death (58% vs. &lt; 49% in other groups). There also were differences in histology; NHW and NHB had a higher frequency of serous tumors ( &gt; 56% of EOCs vs. &lt; 52% in other groups); PI had a high proportion of endometrioid histology (14% of EOCs vs. &lt; 11% in others); 10% of EOCs among AS had clear cell histology (vs. &lt; 9% in others). HS had a high percentage of local disease (23% vs. &lt; 20% in others). In multivariable survival analysis adjusting for clinical factors, we observed that compared with NHW, there were no differences in EOC survival by race/ethnicity: AS, HR = 0.80 (95% CI = 0.61-1.05); NHB, HR = 0.96 (95% CI = 0.72-1.28); PI, HR = 0.92 (95% CI = 0.58-1.46); and HS, HR = 0.82 (95% CI = 0.56-1.21). Conclusions: We observed no racial/ethnic disparities in EOC survival in a Military equal access treatment environment. These results highlight the importance of studying how differences in access to healthcare may impact observed racial/ethnic disparities for EOC.
Ethnic health inequalities: turning evidence into action
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

A year ago, NHS England announced that an organisation should be established1 to identify and tackle the health inequalities facing people from ethnic minority backgrounds. It came after The BMJ highlighted the effects of racism on patients and doctors in a special issue last February (www.bmj.com/racism-in-medicine). The Race and Health Observatory’s first director, Habib Naqvi, tells Zosia Kmietowicz about his plans and ambitions.

> It’s been a fantastic six months. I’ve been given a blank sheet to establish the observatory and it’s been a bit like building a plane while in flight—we’re establishing the architecture and infrastructure while also delivering outputs. We’ve pulled together a fantastic board of experts in inequality, health inequalities, and racial equality2 (see box) and the observatory officially started in April. The diverse representation of the board with its high level of expertise, knowledge, diversity of thought, and innovation is exactly what we need to shift the dial on inequalities in health.
> 
> At the same time there’s been a level of urgency and expectation for delivery. We’ve completed several pieces of work, including some that can have an immediate impact on patients and communities with regards to the pandemic. For example, we’ve been working with the London School of Hygiene and Tropical Medicine on the uptake of the covid-19 vaccine among health and social care staff—we hope to publish on this soon, highlighting some lessons in terms of how the NHS can support frontline staff. But we’ve also been thinking about deep rooted problems that we need to focus on. …
Clinical presentation and outcome of patients with AL amyloidosis requiring salvage therapy.
Authors: Chen Wang, Yumeng Zhang, Lauren Duncanson, Jason B. Brayer, Doris K. Hansen, Melissa Alsina, Taiga Nishihori, Hien Liu, Jose L. Ochoa-Bayona, Kenneth H. Shain, Frederic J. Reu, Rachid C. Baz, Brandon Jamaal Blue
Journal: Journal of Clinical Oncology (2021)

e20043 Background: The diagnosis and upfront management of immunoglobulin light chain (AL) amyloidosis have greatly improved in recent years. However, little is known about the presentation, treatment, and outcome of these patients at first relapse/progression (R/P). Methods: All patients with AL amyloidosis who received salvage therapy for first R/P disease at Moffitt Cancer Center between 2008 and 2020 were included in this retrospective review. Definitions of hematologic and organ R/P were based on 2012 consensus. Overall survival was measured from the time of salvage to last follow up/death. Survival was assessed by Kaplan-Meier with log-rank comparison. Results: Sixty-nine patients were included. The median age at diagnosis was 62 years and 61% were male. Upfront therapy included high dose melphalan with autologous transplant in 36% and bortezomib in 52%. At salvage, 19% had disease refractory to upfront therapy and 40% had not achieved an organ response. The median time from upfront to salvage therapy was 22 months. Salvage regimens included proteasome inhibitors, daratumumab and immunomodulatory drugs in 55%, 13% and 22%, respectively. At least a very good partial response and organ response were achieved in 35% (22/62) and 39% (21/54) with measurable disease. The median overall survival was 60 months. Based on salvage indication, patients were classified into hematologic (n = 29) and organ R/P (n = 40), and the latter showed more frequent lambda-light chain disease (59% vs. 83%, p = 0.028) and low difference of involved-uninvolved free light chain at diagnosis (&lt; 50 mg/L, 8% vs. 44%, p = 0.002). Negative prognostic markers for survival included bone marrow plasma cells ≥20% at diagnosis (median 17 months vs. not reached; p &lt; 0.001) and organ, particularly cardiac R/P (median, 31 months vs. not reached; p = 0.003). Salvage ( p = 0.48) or prior regimens ( p = 0.11) did not impact post-salvage survival. Conclusions: Our study highlights the unmet need of salvage in R/P AL amyloidosis in a real-world setting, given the low rate of deep responses regardless of current salvage options. Patients with bone marrow plasma cells ≥20% at diagnosis and organ R/P at salvage had inferior survival, supporting use of intensive upfront regimens for the former and adjustment of therapy if deep response is not achieved.[Table: see text]
Online CME closes gaps in CSCC management revealed in a virtual patient simulation.
Authors: Shari Dermer, Briana Betz, Piyali Chatterjee-Shin, Vishal Patel, Nikhil I. Khushalani
Journal: Journal of Clinical Oncology (2021)

e23013 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer type. Although highly curable in its early stages, advanced or metastatic CSCC has been associated with mortality rates as high as 70%. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists on the assessment and management of CSCC. Methods: The educational series consisted of 4 online, CME-certified activities in multiple delivery formats, including an initial virtual patient simulation, followed by a clinical practice assessment (CPA) and 2 video discussions with synchronized slides. For the video discussions, educational effect was assessed with a repeated pairs pre-/post-assessment study including a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question, with each participant serving as his/her own control. To assess changes in knowledge, competence, and confidence data from all clinicians who completed both pre- and post-questions were aggregated across activities and stratified by learning theme. McNemar’s test or paired samples t-test ( P &lt;.05) assessed educational effect. The first activity launched June 2019 and the last launched August 2020; data were collected until December 2020. Results: Following education oncologists had significant improvements in knowledge and competence compared with responses from the CPA. Improvement in knowledge and competence measured as relative % change in correct responses pre/post education across the learning themes identified in the virtual patient simulation are reported: Identifying patients who are not candidates for surgical intervention: 9% increase (56% CPA/ 77% pre/ 84% post; n=123-314; P &lt;.05). Tailoring treatment: 30% increase (41% CPA/ 56% pre/ 73% post; n=119-314; P &lt;.05). Tailoring treatment–cemiplimab: 22% increase (32% CPA/ 55% pre/ 67% post; n=123-314; P &lt;.05). Tailoring treatment–cetuximab: 16% increase (15% CPA/ 37% pre/ 43% post; n=123-314; P &lt;.05). New and emerging immunotherapies for CSCC: 47% increase (28% CPA/ 30% pre/ 44% post; n=119-314; P &lt;.05). Conclusions: These results demonstrate the effectiveness of curriculum-based education for oncologists to address specific gaps in care as identified in a virtual patient simulation. This series of CME-certified online educational activities resulted in significant improvements in knowledge and competence in the assessment and treatment of patients with CSCC.
Assessment of objective response rate (ORR) by investigator versus blinded independent central review in pivotal trials of drugs approved for solid tumor indications.
Authors: Marjorie E. Zettler, Choo H. Lee, Ajeet Gajra, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2021)

e13570 Background: Objective response rate (ORR), defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST), is the most common endpoint used in pivotal trials supporting FDA approval of cancer drugs for solid tumor indications. Blinded independent central review (BICR) is frequently employed in clinical trials to minimize bias in evaluation of response rate, as historically, assessment of response by investigators (INV) has been shown to overestimate treatment effect. In this study, we analyzed the variability in assessment of ORR between INV and BICR in trials supporting recent Food and Drug Administration (FDA) approvals of drugs for solid tumor indications. Methods: The FDA’s novel drug approvals (2015-2019) were reviewed to identify drugs receiving primary approval for solid tumor indications. Drug approval packages accessed via the Drugs@FDA database and primary publications for the pivotal trials accessed via PubMed were reviewed for investigator-assessed and BICR-assessed ORR. For trials reporting both assessments, the difference between INV and BICR ORR was determined across all study arms. Data are presented using descriptive statistics. Results: A total of 36 drugs received primary approval for the treatment of solid tumors between 2015 and 2019. Of the 40 supporting trials, ORR was the primary endpoint for 21 (52.5%), progression-free survival for 13 (32.5%), and overall survival for 2 (5.0%). ORR was evaluated in 35 of the 40 trials (87.5%). Eight (22.9%) of the 35 trials evaluated INV ORR only, 5 (14.3%) evaluated BICR ORR only, and 22 (62.9%) evaluated both INV and BICR ORR. Among the 22 trials (29 arms in total), the mean difference between BICR- and INV-assessed ORR was -4.3% (95% CI: -6.4, -2.3); the range was -13.1 to 5. INV-assessed ORR was greater than BICR-assessed ORR in 22 of 29 arms (75.9%). The mean difference between BICR- and INV-assessed ORR among the 6 arms representing placebo or active control was -6.0 (95% CI: -11.0, -0.9), compared with -3.9 (95% CI: -6.3, -1.5) among the 23 experimental arms. Conclusions: Compared with BICR, INV overestimated ORR in three-quarters of the trial arms, including those representing control and experimental treatments. Despite this variability, for one fifth of the trials supporting approval of drugs to treat solid tumors, INV was the only method used to assess ORR. For consistency, and the ability to make relative cross-trial comparisons of ORR between agents, BICR should be considered for evaluation of tumor response in all registrational trials.