Markham, Merry Jennifer

PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32–1.67]); Black patients (aOR 1.74; 95 CI 1.24–2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70–6.79) and Other (aOR 2.97; 95 CI 1.71–5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83–12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63–3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20–2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66–3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89–22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701 .

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

PURPOSE: The 21st Century Cures Act mandates the immediate release of clinical information (IRCI) to patients. Immediate sharing of sensitive test results to patients with cancer might have serious unintended consequences for patients and providers. METHODS: A 22-question REDCap survey was designed by the Association of American Cancer Institutes Physician Clinical Leadership Initiative Steering Committee to explore oncology providers' opinions on IRCI policy implementation. It was administered twice in 2021 with a 3-month interval. A third survey with a single question seeking providers' opinions about their adaptation to the IRCI mandate was administered 1 year later to those who had responded to the earlier surveys. The data were analyzed using descriptive statistics such as chi-squared or Fisher's exact tests for categorical variables. The survey was sent to all Association of American Cancer Institutes cancer center members. In the first or second administration, 167 practitioners answered the survey; 31 responded to the third survey. RESULTS: Three quarters of the providers did not favor the new requirement for IRCI and 62% encountered questions from patients about results being sent to them without provider interpretation. Only half of the hospitals had a plan in place to deal with the new IRCI requirements. A third survey, for longitudinal follow-up, indicated a more favorable trend toward adoption of IRCI. CONCLUSION: IRCI for patients with cancer was perceived negatively by academic oncology providers after its implementation. It was viewed to be associated with higher levels of patient anxiety and complaints about the care delivered. Providers preferred to discuss test results with patients before release.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

e24125 Background: Gynecologic, gastrointestinal (GI), and thoracic cancers account for significant morbidity and mortality in the U.S. Women with these types of cancers frequently experience psychological distress, among other poor outcomes. Previous research has indicated that mindfulness-based interventions, such as yoga, can be effective in decreasing distress in cancer patients. Notably, this research has primarily been conducted in a breast cancer population with limited research assessing the feasibility, acceptability, and/or efficacy of this type of intervention in other prevalent and impactful cancers among women. The purpose of the present study was to assess the Feasibility and Acceptability of a yoga intervention for women with gynecologic, GI, or thoracic cancers. Methods: A total of 124 women diagnosed with a gynecologic, GI, or thoracic cancer in the prior year were recruited via outpatient oncology clinics to participate in a 10-week, group-based manualized yoga intervention entitled “Stilling the Waters of Uncertainty” (Author: E. Kacel) that is nearing the end of accrual. Participants completed an Acceptability evaluation following each yoga session with ratings on a 5-point Likert scale from “not at all” to “extremely.” Feasibility of the study was operationalized as percentage of eligible participants who (a) enrolled, (b) attended sessions, and (c) completed post-intervention assessment. Acceptability was operationalized as the percentage of participants with average session ratings of “very” or “extremely” for intervention usefulness, enjoyableness, safety, clarity, relevance, and likelihood of continuing to practice skills. Criteria for operationalizing Feasibility and Acceptability for this study were defined a priori based on recommendations of Bowen and colleagues (2009). A minimum of 80% for each measure of feasibility and acceptability was set as the a priori threshold of success in each domain. Results: All measures of Feasibility were below the a priori benchmark of 80%: Of the 318 eligible patients approached for participation, (a) 124 patients (39.0%) enrolled; 49/124 (39.5%) attended at least 1 yoga session; 44/124 (35.4%) attended at least 8 sessions; and (c) 41/124 (33.1%) completed post-intervention assessment procedures. At least 80% of attendees rated the intervention as “very” or “extremely” useful, enjoyable, safe, and clear; 75.5% and 79.6% of attendees rated the intervention as “very” or “extremely” relevant and likely to be continued to be practiced. Conclusions: The results of this study indicate that a yoga intervention for women with prevalent non-breast cancer types did not meet a priori criteria for feasibility. However, participants who attended at least 1 session rated the intervention as generally acceptable. Future research is needed to improve study/intervention feasibility in this population. Clinical trial information: NCT03385577.

12129 Background: Depression, anxiety, and fear of cancer recurrence (FCR) constitute prevalent psychological concerns necessitating further attention in developing supportive care interventions for women with gynecologic, gastrointestinal, and thoracic cancers. Recent evidence indicates that such concerns may be especially severe among underserved women of color and women affected by low-socioeconomic status (SES). The purpose of the present study is to evaluate the magnitude of changes in depression, anxiety, and FCR associated with a mindfulness-based yoga intervention among a diverse sample of women with these cancers. A second aim is to identify how changes in these concerns may differ across sociodemographic groups. Methods: Women with gynecologic ( n=86), gastrointestinal ( n=17), or thoracic ( n=20) cancers were enrolled in a group-based 10-week yoga intervention utilizing mindfulness meditation, relaxation, and gentle yoga. Prior to and following intervention, participants were administered assessments, including the Beck Depression Inventory – Second Edition (BDI-II) to measure depression, the State-Trait Anxiety Inventory (STAI) to assess anxiety, and the Fear of Cancer Recurrence Inventory (FCRI) to evaluate aspects of FCR. Mixed-linear models evaluated change in outcomes from pre- to post-intervention, with conditional models assessing the effects of age, race/ethnicity, and SES on change. Analyses were conducted prior to trial completion due to approaching accrual period termination. Results: The sample demonstrated a mean age of 58.46 ( SD=10.82) and mean SES score of 3.98 ( SD=1.55) using a 1 to 7 composite scale. Twenty-six percent of participants were of racial and/or ethnic minority status ( n=32). Significant declines in total depressive symptoms, somatic depressive symptoms, state anxiety, and psychological distress due to FCR were observed across the sample. Higher SES was associated with significantly greater reductions in total depressive symptoms and affective depressive symptoms, specifically. Women of color experienced significantly greater declines in somatic symptoms compared to non-Hispanic White women. Conclusions: This mindfulness-based yoga intervention was associated with significant reductions in depressive symptoms, state anxiety, and psychological distress related to FCR among women with gynecologic, gastrointestinal, and thoracic cancers. Higher SES and underserved race/ethnicity status moderated some of these effects. Future research should explore the efficacy of this intervention among diverse women in a randomized clinical trial context. Clinical trial information: NCT03385577.

The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.