tbuckley/cabot-search huggingface dataset:
Genetic counseling and subsequent cascade genetic testing for women with a family history of pathogenic BRCA1 mutation: A cost-effectiveness model.
Authors: Allison Walker, Briana Marmelstein, Corrine Fillman, Monica Dillon, Ashley Graul
Journal: Journal of Clinical Oncology (2024)

10621 Background: BRCA1 pathogenic mutations significantly increase the lifetime risk for breast and ovarian cancer, but risk reducing interventions such as bilateral salpingo-oophorectomy (RRBSO) and mastectomy (RRM) can improve outcomes. For women with a known family history of pathogenetic mutation, genetic counseling and testing is recommended. We sought to determine the cost-effectiveness (CE) of referral to genetic counseling with subsequent cascade testing. Methods: A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine genetics consultation with Ambry panel testing versus no referral. It was assumed that known BRCA1 carriers would undergo annual breast cancer screening with mammogram and MRI at 25yo, RRBSO at 35yo, and RRM at 40yo. Non-carriers underwent routine annual mammogram at 40yo. Additionally, women who did not undergo genetic testing initially do so at the time of diagnosis of first cancer (breast of ovary) and subsequently underwent all recommended risk reducing strategies if found to have a pathogenic BRCA1 mutation. Outcomes included cost, quality adjusted life years (QALYs), ovarian and breast cancer cases and deaths. Univariate and multi-variate analyses were used to investigate the impact of the strategies. Results: In a Monte Carlo Microsimulation cohort of 10,000 women with a first degree relative with a pathogenic BRCA1 mutation, referral to genetic counseling with testing was the dominate strategy. This strategy resulted in a similar mean cost ($185,543 vs $185,171), but with 2,322 additional QALYs and incremental CE ratio (ICER) of 1,605 per QALY. This dominant strategy also resulted in 73 fewer ovarian cancer cases and 545 fewer breast cancer cases. Sensitivity analysis for the age of RRM was remarkable for an annual reduction in breast cancer cases by 97 cases and an annual cost savings of 375,658 for year prior to age 40 that mastectomy was performed. Conclusions: Routine genetic counseling and screening for all patients with a known family history of pathogenic BRCA1 mutation reduces breast and ovarian cancer diagnoses by prompting risk-reducing procedures without significant increase in cost when compared to diagnosis-based testing. Routine access to genetic counseling in a high-risk population would help inform earlier counseling and further decrease cancer risk, particularly as earlier RRM may improve outcomes. This is further supported by the low cost to implement. Improvement in identification and early referral could be targeted. [Table: see text]
Clinical applicability of guideline-recommended molecular targets and genome-targeted cancer therapies.
Authors: Ariadna Tibau, Thomas J. Hwang, Jerry Avorn, Aaron S. Kesselheim
Journal: Journal of Clinical Oncology (2024)

11049 Background: Genomic testing has expanded the possibilities of precision medicine, particularly for advanced, treatment-resistant cancer cases. However, the clinical relevance of most genetic alterations remains uncertain, which can lead physicians to overestimate the benefits of tailored therapies. The National Comprehensive Cancer Network (NCCN) guidelines are cancer-specific treatment recommendations that often determine insurance coverage. We assessed the evidence for clinical benefit and actionability of molecular targets for genome-targeted cancer drugs recommended by NCCN. Methods: We identified genome-targeted therapies for solid cancers from the most recent NCCN guidelines. Trial design characteristics were obtained from publications supporting the NCCN recommendations. Genome target actionability was assessed with the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). This ranges from genome alternation-therapy combinations that lead to improved outcomes (Tier I) to treatments with potential clinical relevance (Tiers II or III) to those with undetermined relevance (Tiers IV to X). Clinical benefit was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT Tier I in combination with a given treatment associated with studies demonstrating substantial clinical benefit by ESMO-MCBS (Grades 4-5) were designated as high-benefit, while those linked to studies achieving an ESMO-MCBS Grade of 3 were categorized as promising but unproven. Results: We extracted411 recommendations from NCCN supporting 74 genome-targeted drugs targeting 50 driver alterations. Most recommendations (346/411, 84%) referred to clinical trial data, while one-sixth (65/411, 16%) relied on case reports or preclinical studies. Clinical trials were mostly Phase I or Phase II (271/346, 78%), single arm (262/346, 76%), and evaluated overall response rate as the primary endpoint (271/346, 78%). Over half of target recommendations had Tier I target actionability (246/411, 60%), over one-third were Tier II or III (142/411, 35%), and the rest were undetermined (23/411, 6%). Among 267 scorable trials,12% (32/267) demonstrated substantial clinical benefit (ESMO-MCBS Grades 4-5) and 45% (121/267) were Grade 3. When combining both frameworks,12% (32/267) genomic-based cancer treatments were high-benefit and 33% (88/267) were promising-but-unproven. Conclusions: About one-eighth of genome-targeted cancer therapies recommended in NCCN guidelines received a high benefit rating, while one-third were identified as having a promising but unproven substantial benefit according to the ESCAT and ESMO-MCBS frameworks. Ensuring NCCN recommendations are aligned with well-documented clinical benefits is crucial for promoting informed, evidence-based genomic-guided treatment decisions.
Decades old communication training influences seen in patient-centric communication skills of transplant hematologists.
Authors: Justine Hung, Rachel Rodenbach, Toby Christopher Campbell
Journal: Journal of Clinical Oncology (2024)

12099 Background: Competency in communication skills was added as a requirement for residencies in 1999. Numerous strategies have since been incorporated into all phases of medical education and beyond. “Ask-tell-ask” and “NURSE” are commonly taught strategies used to guide conversations between physicians and patients. “Ask-tell-ask” provides a structure for assessing and delivering medical knowledge to a patient. “NURSE” outlines methods for incorporating empathy into the medical provider’s statements. We evaluated for the presence of these communication strategies in a high-stakes discussion between a transplant hematologist and a simulated patient facing a new diagnosis of high-risk myelodysplastic syndrome (MDS). Methods: This is a sub-analysis from a mixed-methods, observational study. Our team recruited hematologists who routinely perform hematopoietic cell transplants and designed a patient scenario of a 67-year-old man with recently diagnosed high-risk MDS referred to hematology. Video-recorded virtual encounters simulated an initial hematology consultation appointment between the hematologist and an actor trained to portray the patient. We analyzed transcripts and coded for themes in the discussion content and structure. We evaluated for the use of known communication strategies “ask-tell-ask”, and “NURSE” empathic responses. Results: Of 37 hematologists from 25 academic centers who participated, 73% reported receiving at least some formal communication training. Hematologists ” when teaching patients about their disease and treatment options. For example, nearly all hematologists opened the encounter by asking the patient a perception question regarding their understanding of their disease; nearly all incorporated at least one "NURSE" empathic statement after telling the patient about their disease and its prognostic implications. Most explored the patient’s goals for treatment and described treatment options utilizing an “ask-tell-ask” approach. Nearly all concluded the encounter with a summary and strategy for next steps. Conclusions: While it is commonly held that teaching communication is difficult, these conversations between hematologists and patient actors show the impact of communication training delivered over the past twenty years through the routine incorporation of well-described strategies of “ask-tell-ask” and "NURSE". This observational study provides a window into how these teachings have permeated into medical practice and hematology/oncology specifically. The incorporation of commonly taught communication strategies into these physician-patient encounters provides evidence that teaching high-quality communication may change physician behavior in a sustained and diffuse way.
Relationship between receipt of combined axillary dissection and nodal irradiation and age.
Authors: Sara Myers, Ann H. Partridge, Laura Elizabeth Warren, Rachel Adams Greenup, Elizabeth A. Mittendorf, Tari A. King, Olga Kantor
Journal: Journal of Clinical Oncology (2024)

11043 Background: Combined axillary lymph node dissection and regional nodal irradiation (ALND+RNI) is the greatest risk factor for breast cancer-related lymphedema (BCRL), a lifelong ailment that negatively impacts quality of life. As disability from BCRL may be particularly profound for adults &lt;45 yo with longer life expectancy, we examined the association of age and other sociodemographics with receipt of ALND+RNI to further our understanding of patients at greatest risk for BCRL. Methods: The National Cancer Database (NCDB) was used to examine age-based differences in receipt of ALND+RNI in patients with stage I-III breast cancer treated from 2018-2020. Cohort characteristics were compared by age (&lt;45 yo, 45-64 yo, and 65 yo). Multivariable regression examined the association between age and ALND+RNI adjusting for relevant factors. Sensitivity analyses explored associations between covariates and combined ALND+RNI by age group. Results: Of 155,010 patients, 5.4% were &lt;45 yo, 47.2% were 45-64 yo, and 47.4% were 65 yo. Clinical and pathological node (cN, pN) positive disease, and receipt of ALND, RNI, and ALND+RNI were more common in patients &lt;45 yo (Table). Age &lt;45 yo was independently associated with ALND+RNI (&lt;45 yo OR 1.40; 45-64 yo OR 1.26 vs 65, p&lt;0.001). Residing in areas with a high proportion of high-school graduates (%HSG), Hispanic ethnicity but not race, and lower income were also associated with ALND+RNI in adjusted analyses (all p&lt;0.05). Medicare (p=0.02 vs private insurance) was inversely associated with ALND+RNI. Among clinical factors, pN+ was the greatest risk factor for receipt of ALND+RNI (all p&lt;0.001 vs pN0). Higher cT, cN1 and cN2 categories, lobular tumors, mastectomy, not receiving endocrine therapy, and having chemotherapy were also associated with ALND+ RNI (all p&lt;0.05). Sensitivity analyses showed that while sociodemographics influenced receipt of ALND+RNI for women 45 yos, only clinical factors were significant for ALND+RNI for &lt;45 yo. Among 45-64 yo, high %HSG (p&lt;0.001) and low household incomes (p&lt;0.01) were associated with ALND+RNI. In the 65 yo cohort, high %HSG (p=0.028), and Asian race (p=0.011) were more likely to receive ALND+RNI while Medicare patients were less likely to have ALND+RNI (p=0.012). Conclusions: Our findings suggests that clinical factors predominate in axillary treatment decisions for younger patients; while sociodemographic factors are more prominent for those 45 yo. Given their higher odds of receiving ALND+RNI, BCRL screening may be especially important in patients &lt;45 yo. Further studies are needed to understand the interplay between age and sociodemographics on receipt of ALND+RNI. [Table: see text]
In-hospital mortality patterns and risk factors in patients with cancer with COVID-19.
Authors: Alexander James Didier, Andrew Campbell, Swamroop Nandwani, Alan Fahoury, Camelia Arsene
Journal: Journal of Clinical Oncology (2024)

e23070 Background: The current body of knowledge regarding outcomes of patients with cancer and COVID-19 is conflicting, with some studies suggesting worsened mortality in those with both diseases This study seeks to shed light on the distinctive factors influencing in-hospital mortality in these two cohorts, providing crucial insights that can guide targeted interventions and enhance healthcare strategies for individuals facing the dual burden of cancer and COVID-19. Methods: We conducted a retrospective review of all patients hospitalized with COVID-19 at our institution between January 1, 2021 and April 1, 2023. Patients were stratified into a cohort of those with cancer and coexisting COVID-19 infection and those with solely COVID-19. The cancer and COVID-19 cohort included patients over the age of 18 who had received treatment for cancer within the last 6 months. Information regarding patient demographic characteristics and comorbidities, as well as in-hospital treatment characteristics and outcomes. We performed descriptive analysis and conducted Chi-squared and t-tests to assess for differences in baseline characteristics between cohorts, then developed Cox proportional hazards models to evaluate risk factors for in-hospital mortality. Results: 456 patients with cancer and COVID-19 were compared with 12,566 patients with only COVID-19. In-hospital mortality was 8.2% in the cancer cohort compared with 9.0% in the COVID-19 only cohort. Patients in the cancer cohort were more likely to be male (55.7% vs 48.2%, p = 0.004), older (71 vs 64 years, p &lt; 0.001) with histories of heart failure (27% vs 21%, p = 0.002), chronic kidney disease (50% vs 39%, p &lt; 0.001), COPD (35% vs 24%, p &lt; 0.001), and anemia (57% vs 24%, p &lt; 0.001). The cancer cohort experienced significantly longer length of stay (9 vs 7 days, p &lt; 0.001). Requirement of mechanical ventilation and ICU stay were similar between groups. Multivariate Cox proportional hazards ratios demonstrated similar mortality between cohorts (HR = 0.863, p = 0.361), with age (HR = 1.041, p &lt; 0.001) and history of acute myocardial infarction (HR = 1.275, p = 0.01) being significant predictors of death. Conclusions: Our study demonstrates the complex relationship between cancer, COVID-19, and in-hospital mortality. Despite differences in baseline characteristics between the cohorts, our findings reveal that, after adjusting for confounding factors, there is no significant disparity in mortality rates between patients concurrently battling cancer and COVID-19 and those solely afflicted by COVID-19. The identification of age and a history of acute myocardial infarction as significant predictors of mortality underscores the need for targeted interventions and vigilant management strategies for individuals facing the dual burden of cancer and COVID-19, ensuring equitable and effective healthcare outcomes in this complicated patient population.
Does the most common gynecological cancer have an awareness blind spot? An Israeli preliminary study.
Authors: Bar Levy, Zvi Vaknin
Journal: Journal of Clinical Oncology (2024)

e22540 Background: Our objectives were to assess the awareness of healthy women who present online to endometrial cancer (EC) symptoms and risk factors among the Israeli population. Methods: A survey regarding awareness of EC symptoms and risk factors was published in secure link on popular Israeli feminine social-media groups ( &gt; 20,000 users), for accurate reach. The survey was conducted during May 2023 just before establishing June as Uterine Cancer Awareness Month by IGCS. 1161 healthy women completed the survey voluntarily and anonymously. Results: Thousand-fifty-six women met the survey’s inclusion criteria. About 90% graduated college, all graduated high-school. The respondents were predominantly non-orthodox Jewish. More than quarter had a healthcare background. About two-thirds visit gynecologist at least once a year and about three-quarters had a gynecological examination in the last year. Most respondents were aware of other gynecological cancers, mainly cervical and ovarian cancers. Only about a quarter of the survey population had some awareness of EC symptoms. Nearly half of study population had some idea about signs and symptoms of any gynecological cancer. Regarding EC, more than a quarter were unaware of vaginal bleeding as an EC symptom and about 90% were unaware of any EC risk factors. More than three-quarters were defined as unaware at all. Only about 1% were fully aware. A statistical trend was observed as women older than 45 were more aware than younger. If a symptom occurs, most declared they would visit a gynecologist and only about 8% would refer to their general-practitioner. Conclusions: In our study population, we observed an extremely-low awareness of the most common gynecological cancer in the industrial world (EC) which has easily diagnosed symptoms and risk factors. This striking findings, in a highly-educated and media-exposed group, are a wakeup-call for policymakers and regulators to take further action in order to achieve earlier diagnosis and curative prognosis in EC patients.
Observed germline BRCA1/2 and TP53 tumor genomic profiling allele frequencies.
Authors: Rebecca Wheeler, Catherine Terhaar, Mark Kruzel
Journal: Journal of Clinical Oncology (2024)

e22533 Background: Tumor genomic profiling (TGP) is increasingly used to assist with cancer treatment planning. While these tests are not intended to find germline variants, they are a possible incidental outcome. Currently there are no clear guidelines on when to suspect if a somatic variant identified on TGP may need confirmatory germline genetic testing. Variant allele frequency (VAF) is one tool commonly used to assess if a variant may be germline. While some studies have demonstrated germline VAF ranges on TGP, the data is limited. The purpose of this study was to review VAF ranges of BRCA1/2 and TP53 variants at a large reference laboratory to better understand VAF ranges of confirmed germline variants. Methods: A retrospective review of test results from 184 patients who underwent TGP and hereditary cancer germline testing at a large reference laboratory was performed. Patients were included in the study if they had both TGP and germline testing performed, regardless of the order of testing. Results were analyzed to determine variants identified and VAF. Analysis of BRCA1/2 and TP53 variants included patients who had variants identified on TGP and had germline testing that would have confirmed the variants if present in the germline. The VAFs were obtained, and simple statistics were used to describe the findings. Results: Twenty-one patients were found to have 23 BRCA1/2 variants identified on TGP (2 patients had 2 BRCA1/2 TGP variants). Of these TGP variants, 16 were confirmed on germline testing (69.6%). The TGP VAF for these patients ranged from 38.2% to 85.1%. The mean was 61.0% and the median was 61.8%. The remaining 7 TGP variants that were not confirmed on germline testing ranged from 7.2% to 63.4%. The mean was 31.1% and the median was 28%. Thirty-eight patients were found to have 41 TP53 variants identified on TGP (3 patients had 2 TP53 TGP variants). Of these patients, 1 had a TP53 variant confirmed on germline testing with a VAF of 44.7%. The 40 remaining variants in this dataset were not confirmed on germline testing. The VAF for these 40 variants ranged from 1.3% to 95.3%. The mean was 38.4% and the median was 34.5%. Conclusions: In this study, 69.6% of BRCA1/2 TGP variants were confirmed on germline testing compared to 2.4% of TP53 TGP variants. Confirmed germline variants identified on TGP had VAFs that were &gt; 38%. It’s important to note that TP53 variants may have very high VAFs (up to 95.3% in this study) and not be.
Biomarker testing and targeted therapy use among patients with non-small cell lung cancer in the United States: An analysis using a physician notes real-world database.
Authors: Vernon Videna, Dave Iwanyckyj, Fernando Otalora, Melanie Jardim
Journal: Journal of Clinical Oncology (2024)

11175 Background: Biomarker testing informs treatment decisions by identifying patients who would clinically benefit from targeted regimens, leading to improved patient outcomes. However, the use of guideline-recommended biomarker testing in patients with advanced non-small cell lung cancer (NSCLC) is inconsistent. This study investigates the rates of biomarker testing in patients with NSCLC using a qualitative, real-world database. Methods: Natural language processing (NLP) was used to search and analyze the Amplity Insights database, consisting of transcribed, de-identified, records of physician-patient interactions obtained from patient medical records across the United States. This was a retrospective analysis of patients with a diagnosis of NSCLC (October 2003 - November 2023). Patient characteristics, biomarker testing, and treatment use were summarized and described. Results: 61,018 patients with NSCLC (mean [standard deviation] age of 69.8 [10.5] years) were identified. Among these, 50.6% were female and 87.9% identified as white. Among records with staging information, 26.6% had early-stage disease (stage 0-II) and 73.4% had late stage (stage III-IV) disease. In total, 13.4% (n=8,151) of all patients received biomarker testing. 13.3% (n=879) and 22.4% (n=2,402) of patients with stage III and IV, respectively, had biomarker testing performed; rates were higher in patients who were receiving care from an oncologist (16.8%, 31.0%, respectively). Among patients who had a confirmed actionable mutation (n=6,387), 35.9% received an appropriately matched targeted therapy and 10.1% received a nonindicated targeted therapy without harboring the indicated mutation. Of these, 40.7%, 22.7%, and 37.7% of patients harbored EGFR or ALK mutations, or were PD-L1 positive, respectively, and 35.8%, 17.8%, and 40.2% received the appropriate indicated treatment, respectively, based on testing. ALK-, EGFR-, and PD-L1-targeted therapies were taken by 12.1%, 9.4%, and 1.9% of patients, respectively, without evidence of the indicated biomarkers. Conclusions: These findings suggest that biomarker testing may be underutilized and that many patients may not be benefitting from treatment with precision therapies, highlighting the need for additional educational strategies to optimize precision oncology and elevate patient outcomes.