Search

Despite their increased enrollment into medical school, women still face systemic barriers in medicine, whether in an academic or nonacademic setting. Those from Under-Represented Minority (URM) groups face similar issues, which may affect their desire to enter, pursue, and/or maintain a career in medicine. Social media provides unique opportunities for peer-to-peer support among members of URM communities and for amplification of their voices calling for social justice—here defined as a redistribution of power and the quest for equity in access to opportunities, including access to mentorship, professional development, and timely promotion in academic rank. These issues are relevant to oncologists especially as we strive for diversity, equity, and inclusion and to ensure that our patients have equal access to care, regardless of their circumstances. In this article, we review current literature that highlights issues faced by women and historically URM groups in medicine, particularly in oncology. We also discuss the physician's role as a social justice advocate and the concept of the public physician.

PURPOSE To update the American Society of Clinical Oncology guideline on the management of anxiety and depression in adult cancer survivors. METHODS A multidisciplinary expert panel convened to update the guideline. A systematic review of evidence published from 2013-2021 was conducted. RESULTS The evidence base consisted of 17 systematic reviews ± meta analyses (nine for psychosocial interventions, four for physical exercise, three for mindfulness-based stress reduction [MBSR], and one for pharmacologic interventions), and an additional 44 randomized controlled trials. Psychological, educational, and psychosocial interventions led to improvements in depression and anxiety. Evidence for pharmacologic management of depression and anxiety in cancer survivors was inconsistent. The lack of inclusion of survivors from minoritized groups was noted and identified as an important consideration to provide high-quality care for ethnic minority populations. RECOMMENDATIONS It is recommended to use a stepped-care model, that is, provide the most effective and least resource-intensive intervention based on symptom severity. All oncology patients should be offered education regarding depression and anxiety. For patients with moderate symptoms of depression, clinicians should offer cognitive behavior therapy (CBT), behavioral activation (BA), MBSR, structured physical activity, or empirically supported psychosocial interventions. For patients with moderate symptoms of anxiety, clinicians should offer CBT, BA, structured physical activity, acceptance and commitment therapy, or psychosocial interventions. For patients with severe symptoms of depression or anxiety, clinicians should offer cognitive therapy, BA, CBT, MBSR, or interpersonal therapy. Treating clinicians may offer a pharmacologic regimen for depression or anxiety for patients who do not have access to first-line treatment, prefer pharmacotherapy, have previously responded well to pharmacotherapy, or have not improved following first-line psychological or behavioral management. Additional information is available at www.asco.org/survivorship-guidelines .

Purpose: This study reports a phase I immunotherapy trial in 23 women with metastatic breast cancer consisting of eight infusions of anti-CD3 × anti-HER2 bispecific antibody (HER2Bi) armed anti-CD3–activated T cells (ATC) in combination with low-dose IL-2 and granulocyte-macrophage colony-stimulating factor to determine safety, maximum tolerated dose (MTD), technical feasibility, T-cell trafficking, immune responses, time to progression, and overall survival (OS).Experimental Design: ATC were expanded from leukapheresis product using IL2 and anti-CD3 monoclonal antibody and armed with HER2Bi. In 3+3 dose escalation design, groups of 3 patients received 5, 10, 20, or 40 × 109 armed ATC (aATC) per infusion.Results: There were no dose-limiting toxicities and the MTD was not defined. It was technically feasible to grow 160 × 109 ATC from a single leukapheresis. aATC persisted in the blood for weeks and trafficked to tumors. Infusions of aATC induced anti-breast cancer responses and increases in immunokines. At 14.5 weeks after enrollment, 13 of 22 (59.1%) evaluable patients had stable disease and 9 of 22 (40.9%) had progressive disease. The median OS was 36.2 months for all patients, 57.4 months for HER2 3+ patients, and 27.4 months for HER2 0–2+ patients.Conclusions: Targeting HER2+ and HER2− tumors with aATC infusions induced antitumor responses, increases in Th1 cytokines, and IL12 serum levels that suggest that aATC infusions vaccinated patients against their own tumors. These results provide a strong rationale for conducting phase II trials. Clin Cancer Res; 21(10); 2305–14. ©2015 AACR.

Methods and Materials, Supplementary Tables S1-S6. Table S1. Patient characteristics: Prior chemotherapy, ER/PR/HER2 status, aATC dose, disease status, survival and time to progression data. Table S2. Dose Escalation Table S3. Characteristics and Activity of Expansion Product Table S4. Clinical Outcomes: Stable Disease at 14.5 Weeks versus Progressive Disease in HER2 negative and HER2 3+ Metastatic Breast Cancer Patients. Table S5. Clinical Responses to HER2Bi-armed ATC by Dose Level in Phase I Metastatic Breast Cancer (HER2/neu 0-3+) at 14.5 Weeks after Last Chemotherapy/Hormone Treatment. Table S6. Shows tumor marker responses in 14 patients post immunotherapy from base line before IT treatment.

PURPOSE: Hematology and oncology (HO) lags behind all medicine subspecialties in fellows under-represented in medicine (URM) despite a growing minority patient population. Websites have been effectively used in URM recruitment. We evaluated all US HO program websites to facilitate a more informed and URM-considerate recruitment. We also performed a stratified analysis on programs affiliated with National Cancer Institute (NCI) Designated Cancer Centers, National Comprehensive Cancer Center Network (NCCN) member institutions, and ranked as a top 50 cancer hospital by US News, given their stated commitment to outreach. MATERIALS AND METHODS: Websites of all 2019-2020 Accreditation Council for Graduate Medical Education–accredited HO programs were assessed for 28 informational and three diversity categories. Websites with > 70% of categories were comprehensive. Affiliation with NCI, NCCN, and US News was noted. RESULTS: One hundred fifty-six websites were analyzed: 20% were comprehensive and 22% had any diversity information. Inclusion of diversity content and being comprehensive were significantly associated ( P = .001). NCI, NCCN, and US News ranking were significantly associated with inclusion of more information in univariate analyses ( P < .001, P = .008, and P < .001, respectively). Multivariate analyses showed that US News ranking was significantly associated with more information ( P = .005). Diversity-related univariate and multivariate analyses showed a significant association with US News ranking ( P = .006 and P = .029, respectively). CONCLUSION: Most HO fellowship websites are not comprehensive and lack diversity content. Given COVID-19 travel restrictions limit in-person interviews, digital program presence remains an important opportunity. HO programs should offer comprehensive and inclusive websites to better inform applicants, including URM. This may increase institutional diversity and potentially improve URM representation in the HO workforce.

Social media growth has revolutionized health care, facilitatinguser-friendly, rapidand global sharing of content. Within oncology, this allows for new frontiers in communication for cancer patients, caregiversand healthcare providers. As more physicians engage in online spaces, it is imperative that there are resources to assist in establishing a professional presence on social media. This article describeshow to create a social media identity, best practices for engaging both in patient and caregiver spaces and professional communities, and how to address antagonistic and inappropriatebehavior on social media with the goal of helping physicians develop an engaging, productiveand enjoyable experience online.

A growing body of research suggests lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) people—referred collectively as sexual and/or gender minorities (SGM)—experience health disparities. While research is growing, limited evidence exists to inform patient-centered care for SGM people. The collection of demographic data is a cornerstone of quality assurance, yet collection of sexual orientation and gender identity (SOGI) data remains challenging and sparse. SGM people share with racial, ethnic, and other minoritized people stigma and suboptimal social determinants of health that may result in chronic stress and poorer health outcomes compared to cisgender, white, heterosexual people. Challenges are compounded for those who occupy multiple minoritized categories. The stigma and discrimination experienced by SGM are critically tied to behavioral risks related to maladaptive coping. Additionally, stigma impacts screening and other healthcare seeking behaviors. To advance SGM health equity, both clinicians and researchers need training on culturally appropriate collection of SOGI data and the relevance of these data to cancer prevention, screening, treatment, and survivorship.

Social media (SoMe) platforms have the ability to strengthen the oncology community, leading to intellectual connections that with time develop into friendships. SoMe has immense potential in all areas of medicine, and SoMe in oncology is proof of this, raising awareness about clinical trials, promoting cancer prevention techniques, amplifying oncology information, enabling diverse viewpoints into conversations, as well as educating colleagues regardless of geography.

Recent years have seen the emergence of immunotherapy as a promising modality for treating a variety of cancers. However, the initial data have led to the ultimate reality that such a treatment does not work effectively in all cancers, nor does it universally result in long-lasting benefits, which can be partly attributed to the development of drug resistance- itself a major challenge. Worse, in some cases, immunotherapy can lead to accelerated tumor growth known as hyperprogression. Tumor sensitization is being pursued as a means to circumvent resistance to immunotherapy, and perhaps as a means to prevent hyperprogression. Such approaches aim to counteract features of immune resistance demonstrated by refractory tumors, paving the way for improved treatment effectiveness when standard immunotherapies such as immune checkpoint inhibitors are utilized. Sensitizing agents can be categorized by whether their target is a tumor-intrinsic or a tumor cell-extrinsic factor. Tumor-intrinsic sensitization strategies act directly on cancer cells, suppressing their anti-immune tendencies, whereas tumor cell-extrinsic sensitization strategies target the tumor microenvironment to more effectively mediate the desired therapeutic effects of immunotherapy.

PURPOSE: Cancer prevalence and outcomes data, necessary to understand disparities in transgender populations, are significantly hampered because gender identity data are not routinely collected. A database of clinical data on people with cancer, CancerLinQ, is operated by the ASCO and collected from practices across the United States and multiple electronic health records. METHODS: To attempt to identify transgender people with cancer within CancerLinQ, we used three criteria: (1) International Classification of Diseases 9/10 diagnosis (Dx) code suggestive of transgender identity; (2) male gender and Dx of cervical, endometrial, ovarian, fallopian tube, or other related cancer; and (3) female gender and Dx of prostate, testicular, penile, or other related cancer. Charts were abstracted to confirm transgender identity. RESULTS: Five hundred fifty-seven cases matched inclusion criteria and two hundred and forty-two were abstracted. Seventy-six percent of patients with Dx codes suggestive of transgender identity were transgender. Only 2% and 3% of the people identified by criteria 2 and 3 had evidence of transgender identity, respectively. Extrapolating to nonabstracted data, we would expect to identify an additional four individuals in category 2 and an additional three individuals in category 3, or a total of 44. The total population in CancerLinQ is approximately 1,300,000. Thus, our methods could identify 0.003% of the total population as transgender. CONCLUSION: Given the need for data regarding transgender people with cancer and the deficiencies of current data resources, a national concerted effort is needed to prospectively collect gender identity data. These efforts will require systemic efforts to create safe healthcare environments for transgender people.

Our Laboratory was established in 1994 at Univ. of Pennsylvania. Lab members demonstrated initial competencies by performing cell culture, western blots, immunofluorescence, and flow cytometry showing induction of p53/p21(WAF1) in cells treated with chemotherapy. Years later, our Laboratory of Translational Oncology & Experimental Cancer Therapeutics moved to Penn State Univ., Fox Chase Cancer Center/Temple Univ. and then Brown Univ. By 2020, with desire for inclusiveness (everyone succeeds), scientific rigor/reproducibility mandated by NIH, and as a training and mentoring activity (lab scientists/trainees/students mentoring others at High School level and beyond), we established a process for onboarding and training new cancer researchers. By Fall of 2022, there were 17 current Brown University undergraduate students (10 receiving research credit and 7 not receiving credit), HS students, 7 graduate students (PhD, masters, MD/PhD), and 6 medical students working with collaborating faculty at our laboratory at Brown’s Legorreta Cancer Center. After completion of biosafety training, and required trainings such as by IACUC, new lab members complete basic competencies in cell culture, cell viability, and western blot analysis that include technical, presentation quality output, and quantitative/statistical rigor to satisfy current standards for journal publication. For cell culture this includes pathogen free conditions, authentication, attention to details of routine procedures, documentation of morphology, freezing, thawing, passaging, seeding density, and managing cell populations to not run out of cells. Cell viability assessment includes attention to culture conditions, synergy analysis, data robustness, and presentation, and for western blots attention to quality of blots, protein quantification, loading, labeling, antibody specificity and sensitivity controls, presentation at 2022 standards, conventions for splicing, and issues with reproducibility including biological replicates, and generalizability. Additional and advanced competencies include RT-PCR, long-term colony assays, 3-D cultures (spheroids, organoids), transfection (overexpression, knockdown, CRISPR), co-culture and triculture with immune cells and fibroblasts, cytokine profiling, in vivo studies, in vivo imaging, immunohistochemistry, flow cytometric analysis, single cell techniques, viral infection, circulating tumor cell isolation, blood immune and cytokine analysis, and work with transgenic organoids and inducible cancer predisposing alleles. Modeling the tumor microenvironment, relevance to human cancer and translational directions are emphasized. Shared online lab resources, protocols, practices, videos, and manuscripts are available for lab members. The framework herein may be of interest to others involved in similar training programs. Citation Format: Wafik S. El-Deiry, Andrew George, Francesca Di Cristofano, Praveen Srinivasan, Lindsey Carlsen, Kelsey E. Huntington, Arielle De La Cruz, Leiqing Zhang, Marina Hahn, Shuai Zhao, Attila Seyhan, Bradley D. DeNardo, Aaron W. Maxwell, Dae Hee Kim, Alex Raufi, Hina Khan, Stephanie L. Graff, Don S. Dizon, Christopher Azzoli, Abbas E. Abbas, Roxanne Wood, Rishi R. Lulla, Howard P. Safran, Benedito A. Carneiro, Arunasalam Navaraj, Xiaobing Tian, Shengliang Zhang, Lanlan Zhou. Inclusive basic and advanced translational laboratory research competencies for research in cancer biology and therapeutics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4185.

BRCA1/2 genes encode proteins that mediate homologous recombination and repair (HRR). BRCA1/2 mutations increase risk of breast, ovarian, prostate and other cancers. BRCA1/2 mutated tumor cells are sensitive to PARP inhibitors (PARPi), that cause DNA replication fork to collapse. Approximately 40% of patients develop PARPi resistance through different mechanisms. One of the mechanisms of PARPi resistance is through P13k/Akt pathway activation. Imipridones are TRAIL-inducing compounds which are PERK-independent activators of the integrated stress response, and dual inhibitors of Akt/ERK. We hypothesized that combining imipridones with PARPi would overcome PARPi resistance due to Akt activation. PARPi also sensitize various solid tumors to recombinant TRAIL and DR5 agonist antibodies thereby further suggesting possible synergies between imipridones and PARPi. Our lab previously showed efficacy of imipridone ONC201 in BRCA-deficient cancer cells and potential synergy with olaparib (2017 AACR annual meeting abstract), without further investigating potential synergistic mechanisms. We explored combination drug synergy of rucaparib (PARP inhibitor) and imipridones (ONC212 and ONC201) in BRCA1/2-deficient breast, ovarian and prostate cancer cell lines. CellTiterGLO viability assays were performed after 72 hours to demonstrate synergistic effects of combination treatment. Western blots were performed to investigate the effect of combination treatment on the Akt pathway, as well as expression of cellular metabolic stress protein ATF4. Cytokine profiling using the Luminex 200 technology was used to study the effect of treatment on the tumor microenvironment. Combination treatment (rucaparib and ONC212, rucaparib and ONC201) in BRCA–deficient cell lines (HCC1937, PEO1, KURAMOCHI, 22RV1, LNCAP) showed synergistic reduction in cell viability. In the HCC 1937 cell line, combination studies of rucaparib-ONC212 and rucaparib-ONC201 showed a synergystic effect, as calculated by Compusyn software, combination indexes below one were observed at concentration of 0.29-37.5 of µM rucaparib with ONC201 at 1.25-5 µM and ONC212 6.25-50 nM with the best combination index of 0.7 for rucaparib-ONC201 combination and 0.31 for rucaparib-ONC212. We similarly observed synergy in other cell lines with combination treatment. Western blot analysis of rucaparib-ONC212 combination showed total Akt protein reduction and an increase in ATF4 consistent with the synergistic effects. Further studies are ongoing to characterize possible mechanisms and effects of PARP inhibitor-imipridone combination treatment on immune-mediated killing. Our findings identify novel PARP inhibitor-imipridone therapy combinations that can be further developed for treatment of BRCA1/2 deficient cancers. Citation Format: Maryam Ghandali, Kelsey E. Huntington, praveen Srinivasan, Don S. Dizon, Stephanie L. Graff, Benedito A. Carneiro, Wafik S. El-Deiry. PARP inhibitor rucaparib in combination with imipridones ONC201 or ONC212 demonstrates preclinical synergy against BRCA1/2-deficient breast, ovarian, and prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1066.

For patients who complete treatment for breast cancer, national oncologic guidelines recommend yearly mammography surveillance and oncology follow-up especially during the first five years of survivorship. Some studies have shown that older age and insurance type may be risk factors for timely initial follow up after abnormal mammogram however the role in which racial and socioeconomic disparities may contribute to long term non-adherence or loss to follow-up (LTFU) is not known. Investigation into causes of LTFU or non-receipt of recommended surveillance are crucial in improving health care delivery and targeting interventions that prevent LTFU in high-risk patients. An ongoing study at Lifespan Breast Oncology aims to evaluate this issue further among patients treated for stage 1-3 breast cancer. We have completed data collection on 139 of 300 eligible patients diagnosed in 2014 and for whom 5 years of follow up have been completed. We measured adherence to yearly mammography, visit with breast oncologist, continuation of ET, and LTFU in each year of survivorship. LTFU was defined as patient without any further contact with the Lifespan Breast Oncology clinic. We then examined the association between these adherence measures and age, ECOG performance status at diagnosis, Medicaid insurance status, socio-economic factors, and specific adjuvant therapies, using univariate and multivariate generalized estimating equation models for longitudinal data. The models reported odds ratios (OR) for non-adherence or LTFU, with 95% confidence intervals (CI). Patients who experienced relapse or death were removed from the pool in the year of event. Adherence decreased for all measures between year 1 and year 5 of survivorship: from 99% to 82% for oncology visits, 92% to 80% for mammography, and 86% to 71% from ET. LTFU increased from 0% to 17%, respectively (OR per year, 1.96; 95%CI, 1.55-2.48). In univariate analysis, patients age >70 (compared with age ≤50) had a significantly higher risk of LTFU (Table), non-adherence to visits (OR=6.64 versus age ≤50, P=.002), mammography (OR=4.18, P=.020), or ET (OR=5.42, P=.002). Patients with performance status ECOG ≥2 had significantly lower adherence to all measures. Medicaid insurance was associated with significantly higher LTFU, non-adherence to mammography (OR=5.58, P=.008) or oncology visits (OR=6.53, P=.002). Marital, employment, or parenting status were not significantly associated with the risk of LTFU, but employed patients had a higher adherence to mammography and ET. Cancer stage, ER, or HER2 status were not associated with any adherence measure. LTFU was lower among recipients of ET, but not recipients of chemotherapy. In a multivariable model, Medicaid insurance (OR=3.99, P=.027) and receipt of ET (OR=0.32, P=.027) retained significant association with LTFU. Our findings show that Medicaid patients represent a high risk group with potential need for increased resources to ensure adequate follow-up. We plan to continue to expand this cohort and analyze more patients at our institution. Interventions to change barriers and circumvent financial limitations that these patients face in obtaining care could potentially decrease rates of recurrence and potentially impact overall survival. This data could be utilized in future studies to create a risk stratification tool to identify patients who would be at high risk for LTFU. Table. Factors associated with loss to follow-up.N (%)% LTFU at 5yOR95%CIPAll13917Age ≤5032 (23)161.00351-7070 (50.4)120.890.27-2.90>7037 (26.6)223.511.19-10.4ECOG 015 (10.8)71.0071108 (77.7)153.650.43-31.1> 214 (10.1)2920.281.90-216Insurance: private78 (56.1)91.001Medicaid15 (10.8)466.762.03-22.5Medicare45 (32.4)195.131.98-13.3Children: no70 (50.4)121.34yes66 (47.5)191.710.56-5.22Married: no56 (40.3)171.68yes83 (59.7)160.840.38-1.88Employed: no70 (50.4)201.32yes66 (47.5)150.660.29-1.49Stage:187 (62.6)181.66239 (28.1)120.640.24-1.69313 (9.4)220.80.19-3.46ER-23 (16.5)261.27ER+115 (82.7)150.580.22-1.54No ET38 (27.3)291.033ET101 (72.7)120.410.18-0.93No chemotherapy87 (62.6)171.25Chemotherapy52 (37.4)160.60.25-1.43 Citation Format: Rani Chudasama, Adam Olszewski, Don Dizon, Mary Anne Fenton. Patient risk factors for loss to breast oncologic follow up [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-57.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.

The Going Flat movement aims to increase awareness and acceptance of mastectomy alone as a viable option for patients. Little is known about motivations and satisfaction with surgical outcomes in this population. An online survey was administered to 931 women who had a history of uni- or bilateral mastectomy for treatment of breast cancer or elevated breast cancer risk without current breast mound reconstruction. Satisfaction with outcome and surgeon support for the patient experience were characterized using 5-level scaled scores. Mastectomy alone was the first choice for 73.7% of the respondents. The top two reasons for going flat were desire for a faster recovery and avoidance of a foreign body placement. Overall, the mean scaled satisfaction score was 3.72 ± 1.17 out of 5. In the multivariable analysis, low level of surgeon support for the decision to go flat was the strongest predictor of a satisfaction score lower than 3 (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.59–5.72; p

PURPOSE Collecting patient-reported outcomes (PROs) can improve symptom control and quality of life, enhance doctor-patient communication, and reduce acute care needs for patients with cancer. Digital solutions facilitate PRO collection, but without robust electronic health record (EHR) integration, effective deployment can be hampered by low patient and clinician engagement and high development and deployment costs. The important components of digital PRO platforms have been defined, but procedures for implementing integrated solutions are not readily available. METHODS As part of the NCI's IMPACT consortium, six health care systems partnered with Epic to develop an EHR-integrated, PRO-based electronic symptom management program (eSyM) to optimize postoperative recovery and well-being during chemotherapy. The agile development process incorporated user-centered design principles that required engagement from patients, clinicians, and health care systems. Whenever possible, the system used validated content from the public domain and took advantage of existing EHR capabilities to automate processes. RESULTS eSyM includes symptom surveys on the basis of the PRO-Common Terminology Criteria for Adverse Events (PRO-CTCAE) plus two global wellness questions; reminders and symptom self-management tip sheets for patients; alerts and symptom reports for clinicians; and population management dashboards. EHR dependencies include a secure Health Insurance Portability and Accountability Act-compliant patient portal; diagnosis, procedure and chemotherapy treatment plan data; registries that identify and track target populations; and the ability to create reminders, alerts, reports, dashboards, and charting shortcuts. CONCLUSION eSyM incorporates validated content and leverages existing EHR capabilities. Build challenges include the innate technical limitations of the EHR, the constrained availability of site technical resources, and sites' heterogenous EHR configurations and policies. Integration of PRO-based symptom management programs into the EHR could help overcome adoption barriers, consolidate clinical workflows, and foster scalability and sustainability. We intend to make eSyM available to all Epic users.

Objective Pegylated liposomal doxorubicin (PLD) in vitro may have immunomodulatory abilities and preclinical evidence suggests it synergizes with immune checkpoint blockade. We hypothesized that combining PLD and pembrolizumab would be active in patients with platinum-resistant ovarian cancer (PROC). Methods This was a single-arm, multi-center phase II trial. Eligible patients had PROC with ≤2 prior lines of cytotoxic therapy for recurrent or persistent disease. Twenty-six patients were enrolled and given pembrolizumab 200 mg intravenously (IV) every 3 weeks and PLD 40 mg/m2 IV every 4 weeks. Patients were assessed radiographically every 8 weeks. The primary endpoint was clinical benefit rate (CBR), defined as complete response (CR) + partial response (PR) + stable disease (SD) ≥24 weeks. The study was powered to detect an improvement in CBR from 25% to 50%, with rejection of the null hypothesis if at least 10 patients achieved clinical benefit. T-cell inflamed gene expression profiles (GEP) and PD-L1 were assessed and correlated with clinical outcome. Results Twenty-three patients were evaluable for best overall response. The study satisfied its primary endpoint, with 12 patients achieving clinical benefit for a CBR of 52.2% (95% CI 30.6–73.2%). There were 5 PRs (21.7%) and 1 CR (4.3%), for an overall response rate (ORR) of 26.1%. Six patients had SD lasting at least 24 weeks. Combination therapy was well tolerated without unexpected toxicities. Conclusions The combination of pembrolizumab and PLD was manageable, without unexpected toxicities, and showed preliminary evidence of clinical benefit in the treatment of platinum resistant ovarian cancer. ORR and median PFS of combination therapy in this study was higher than historical comparisons of PLD alone or anti-PD-1/PD-L1 agents alone. Trial Registration: Clinicaltrials.gov identifier: NCT02865811

In H+BC, neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates, but the most common anthracycline-free regimen, every 3-week docetaxel and Cb with T and P (TCHP), causes significant hematologic and non-hematologic toxicities. We conducted a pilot study to assess the efficacy and toxicity of a weekly anthracycline-free regimen, and to assess whether patients (pts) with a suboptimal response to this regimen benefit from switching to doxorubicin/cyclophosphamide (AC). Methods Pts with clinical stage II-III H+BC receive wP 80 mg/m2 and Cb AUC 2 weekly with every 3-week T and P (wPCbTP). Investigators may split the week 1 loading dose of P (840 mg) into two weekly doses, and hold the 2nd dose for early onset toxicity, particularly diarrhea. Pts are restaged after 12 weeks with ultrasound or MRI. Responding pts receive another 6 weeks of wPCbTP, while nonresponders are switched to AC x 4, followed by surgery. Study participation is complete after a 3-month post-op visit. Dose modifications and post-op therapy are at investigator discretion. Results Enrollment (30 pts) is complete. Pathologic findings are available for 23 pts; the other 7 are due to undergo surgery by 10/2019. No pts have required switching to AC for suboptimal response at week 12; 2 have been switched for toxicity (1 each for diarrhea and recurrent cytopenias). pCR (T0/isN0) rates are tabulated below: Pt grouppCR% (95% CI)All18/2378 (56-92) %ER(-)10/1191 (59-100) %ER(+)8/1267 (35-90) %Operable (Stage IIA-IIIA)14/1782 (57-96) %Inoperable (Stage IIIB-C)4/667 (22-96) % In 23 pts, grade 3/4 toxicities observed include neutropenia (10/2, but no febrile neutropenia), anemia (3/0), thrombocytopenia (1/0), diarrhea (4/1), and 5 cases of grade 2 (but no grade ≥3) peripheral neuropathy. One pt each has required hospitalization for recurrent urinary tract, port site or breast infections while not neutropenic. wP has been dose-reduced for neuropathy after week 12 in 8 pts. Two pts discontinued Cb after hypersensitivity reactions in week 10. Treatment was discontinued during weeks 12-18 in 8 pts. P was held during weeks 1-6 for diarrhea in 5 pts and discontinued before week 12 in 3 pts; splitting the loading dose of P has not substantially reduced the incidence or severity of diarrhea. Conclusions Treatment with wPCbTP is associated with a high pCR rate (78%), comparable to those reported with TCHP in multicenter phase II-III trials, and is generally well tolerated, with fewer grade ≥3 toxicities, though diarrhea remains a concern. In some pts, cumulative toxicities make it difficult to continue treatment beyond week 12. Thus far, we have failed to identify a subset of pts in whom to test the efficacy of switching to AC after a suboptimal response to wPCbTP. This regimen appears to be worth exploring further, though we might consider switching to a less toxic regimen, or taking pts with an excellent response to surgery, after week 12. Supported by LifeCycle and the Lura Cook Hull Trust Citation Format: Mary Lorraine Lopresti, Jessica J. Bian, Bachir J Sakr, Rochelle S Strenger, Robert D. Legare, Mary Anne Fenton, Sabrina M Witherby, Don S Dizon, Sonali V Pandya, Ashley R Stuckey, David A Edmondson, Jennifer S Gass, Christine M Emmick, Theresa A Graves, Marlene Cutitar, Adam J Olszewski, William M Sikov. Neoadjuvant weekly paclitaxel (wP) and carboplatin (Cb) with trastuzumab (T) and pertuzumab (P) in HER2-positive breast cancer (H+BC): A Brown University oncology group (BrUOG) study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-19.

Background: The prognosis of patients with estrogen receptor positive (ER+) bone-only metastatic breast cancer (B-MBC) is good, with the average life expectancy extending years with contemporary management. In the general population, studies investigating the impact of screening programs designed to detect disease as early as possible in otherwise asymptomatic patients have consistently shown reduction in morbidity and mortality but outcomes among patients living with B-MBC has not been adequately addressed. This study aimed to investigate the rate at which patients with ER+ breast cancer metastatic only to bone underwent cholesterol, breast cancer, colon cancer, and lung cancer screening and to determine if this screening had any impact on overall survival and cause of death. Methods: We conducted a retrospective chart review of patients treated for ER+ B-MBC at the Lifespan Cancer Institute in Providence, RI between 1/1/15 and 5/31/18. Each patient’s medical records and tumor registry information were reviewed. Data on these patients’ disease history were collected along with data on cholesterol, breast cancer, colon cancer, and lung cancer screening. Descriptive statistics were calculated using STATA statistical software. Results: A total of 48 patients with ER+ B-MBC were identified. Median overall survival from initial diagnosis of breast cancer was 148 months; measured from the diagnosis of bone metastasis, it was 52.4 months. Twenty-nine out of the 48 patients received cholesterol screening (60%), 14/48 had mammograms (29%), and only 8/48 had colonoscopy (17%). No patients underwent screening lung CT (Table 1). Compared to those who did not undergo screening, patients who were screened for cholesterol had significantly longer median overall survival (175.4 vs 106 months, respectively, p=.02) and those undergoing mammogram had a trend towards longer survival (187 vs 131 months, p=.08). Screening was not associated with a difference in rates of death attributed to breast cancer. No deaths due to other malignancies were identified. Of those undergoing mammography, only one abnormal report was identified, and biopsy of the lesion was benign. Table 1: Rate of abnormal screening results, median overall survival from index diagnosis, and death from index breast cancer.Abnormal screening resultMedian OS (months)95% CIp valueDeath from IBCp valueCholesterolscreened18/25175.4135 - 2160.02**1/20.30not screened10668 - 1445/6Mammogramscreened1/14187116 - 2590.08*3/40.60not screened131101 - 1626/10OS=overall survival. CI=confidence interval. IBC=index breast cancer. ** = p < 0.05. *= p < 0.1 Conclusions: A large proportion of patients with B-MBC undergo primary preventative screening measures, and of these, cholesterol screening is the most common. Screening was associated with longer overall survival, but did not change the rates of death due to breast cancer. These results suggest that clinicians are offering screening to a subgroup of women who are healthy despite B-MBC. However, our data suggest there is little benefit to screening, and this should be addressed in a larger dataset. Citation Format: Kristina A Fanucci, Mary Anne Fenton, Christine Duffy, Camille Higel-McGovern, Don Dizon. For women with bone-only metastatic breast cancer, is there a benefit to primary prevention? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-13.

Rationale: Choosing Wisely: In an era of genomic medicine, what role does nodal information play in decisions regarding adjuvant chemotherapy for early-stage, hormone receptor-positive breast cancer ? Authors: Fowler RL, Lew KP, Dizon DS, Ciambella CC, Wakeley M, Taneja C, Wiggins DL, Lopresti ML, Constantinou M, Strenger R, Wang Y, Fenton MA, Graves TA. BACKGROUND/OBJECTIVES: For women with hormone receptor-positive (HR+) breast cancer, the Recurrence Score (RS) informs prognosis and impacts treatment decisions; whether and to what degree nodal information impacts these decisions is not clear. We conducted a retrospective review of patients with newly diagnosed HR+ early stage breast cancer who underwent a sentinel lymph node biopsy (SLNB) and had the RS obtained to discriminate the impact both evaluations had on the use of adjuvant chemotherapy. We hypothesized that for these patients, the RS supersedes nodal information in determining adjuvant treatment. METHODS: 416 patients with T1 to T2 breast cancers seen at our multidisciplinary clinic between 2013 and 2017 were identified. Data collected included demographics, node stage, RS, and adjuvant therapies. RS was stratified in to High, Intermediate, and Low Risk according to criteria used in the TAILORx trial. Continuous variables were analyzed using descriptive statistics and categorical variables were analyzed by Chi-Square or Fisher’s Exact Test. All statistics were performed using STATA 15.0. RESULTS: For this cohort, the median age was 59 years (range 27-79). The vast majority (94%) underwent initial surgical excision or mastectomy with SLNB. Of these, 338 patients (81%) had node-negative disease. Of the remaining, 37 patients (8.9%) had micro-metastasis to a single node, 39 (9.3%) had N1a disease, including one patient with 3 positive lymph nodes. RS risk was characterized as high, intermediate, and low in 12, 65, and 23%, respectively. On multivariate analysis, only age at diagnosis (p0.05). CONCLUSIONS: For women with early-stage, clinically node-negative, HR+ breast cancer, the RS and age of the patient was associated with the administration of adjuvant chemotherapy. Although these data are limited to recommendations surrounding adjuvant chemotherapy and not decisions surrounding adjuvant radiation therapy, these data support the Choosing Wisely™ campaign against routine use of SLNB in low-risk patients. Citation Format: Rachel L Fowler, Kaitlyn P Lew, Don S Dizon, Chelsey C Ciambella, Michelle Wakeley, Charu Taneja, Doreen L Wiggins, Mary L Lopresti, Maria Constantinou, Rochelle Strenger, Yihong Wang, Mary A Fenton, Theresa Graves. The impact of recurrence score versus sentinel lymph node biopsy on treatment decisions in early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-20.

Social media integration into research has increased, and 92% of American social media participants state they would share their data with researchers. Yet, the potential of these data to transform health outcomes has not been fully realized, and the way clinical research is performed has been held back. The use of these technologies in research is dependent on the investigators’ awareness of their potential and their ability to innovate within regulatory and institutional guidelines. The Brown-Lifespan Center for Digital Health has launched an initiative to address these challenges and provide a helpful framework to expand social media use in clinical research.

UNSTRUCTURED Social media integration into research has increased, and 92% of American social media participants state they would share their data with researchers. Yet, the potential of these data to transform health outcomes has not been fully realized, and the way clinical research is performed has been held back. The use of these technologies in research is dependent on the investigators’ awareness of their potential and their ability to innovate within regulatory and institutional guidelines. The Brown-Lifespan Center for Digital Health has launched an initiative to address these challenges and provide a helpful framework to expand social media use in clinical research.

Simple Summary Angiosarcomas (AS) are rare, highly aggressive sarcomas with limited therapeutic options. Genomic sequencing techniques have identified recurrent genetic abnormalities. Nevertheless, the association of these findings with etiology, site of origin, prognosis, and therapeutic implications is not well understood. We analyzed Next Generation Sequencing (NGS) and Whole Transcriptome Sequencing (WTS) data in a cohort of 143 AS cases. We identified distinct genomic biology according to the AS primary site. Head and neck AS cases primarily have Immunotherapy (IO) response markers and mutations in TP53 and POT1. On the other hand, breast AS is enriched for cell cycle alterations, predominately MYC amplification. Additionally, a microenvironment with abundant immune cells is present in a minority of cases but distributed evenly among primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS according to its biology at different primary sites. Abstract We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.

243 Background: Patients (pts) undergoing surgery for suspected malignancy may experience burdensome post-operative symptoms which can compromise outcomes and necessitate acute care. In prior randomized controlled trials at academic medical centers, patient-reported outcome (PRO)-based symptom management solutions improved clinical outcomes. Attempts to generalize this approach to real-world surgical pts have been challenged by perceptions that severe symptoms rarely occur, responding to severe symptoms can be burdensome, and uncertainty about which symptoms are likely to be severe and need interventions. Methods: Six US-based healthcare systems deployed eSyM, an EHR-integrated symptom management program. Pts undergoing surgery for suspected or confirmed thoracic (THOR), gastrointestinal (GI), and gynecologic (GYN) malignancies received automated questionnaires via MyChart portal 1-3 times weekly for up to 3 months after discharge. Questionnaires based on the PRO-CTCAE included 10 required and 20 optional symptoms, all scored as 0 (no symptoms), 1 (mild), 2 (moderate), or 3 (severe). Additional questions assessed functional status, overall wellbeing, wound discharge, and wound redness. Frequency and predictors of severe reporting were assessed using descriptive statistics and logistic regression modeling. Results: 21,012 surgical eSyM questionnaires were submitted between October 2019 - March 2022 by 3,781 unique pts (median age 63 years, 66.9% female, 92.1% white, 57.9% married, and 37.5% retired). 17% of questionnaires (16% of GI, 14% of GYN, and 21% of THOR) included at least 1 severe symptom. Frequencies of severe symptom reporting appear in Table with physical function impairment, general pain, and fatigue as the top three. Severe symptoms were more likely to be reported by younger, female, or unemployed pts(p < 0.01). In comparison to GI pts, GYN pts reported fewer and THOR pts reported more severe symptoms (p < 0.03). Conclusions: A meaningful minority of pts reported severe symptoms, suggesting that symptom monitoring could benefit pts without over-taxing clinicians. There were few strong patient-level predictors of severe symptoms, arguing that population surveillance may be preferable to targeted surveillance. Interventions are needed to address common severe symptoms and future studies should define most effective mitigation strategies for these symptoms. Clinical trial information: NCT03850912. [Table: see text]

241 Background: Monitoring electronic patient-reported outcomes (ePROs) improves quality of life, reduces acute care, and extends survival in cancer patients. Different modalities for collecting ePROs exist. Many efforts focus on mobile apps, but optimal methods for reporting are not well established. We sought to determine whether patient engagement and symptom reporting patterns differed by submission modality. Methods: Through the SIMPRO Consortium, ePRO questionnaires (eSyM) were collected from medical oncology (MO) and surgical (SUR) patients at six health systems between September 2019-March 2022. Questionnaires assessing 12 symptoms plus functional status and overall wellbeing were sent 2-3 times per week via patient portal and made accessible through two modalities: a web platform or mobile device app (mobile). Patterns and predictors of reporting modality were ascertained using descriptive statistics and logistic regression. Results: In total, 6460 patients submitted 47,736 questionnaires: 74% via web and 26% via mobile. Of 2679 MO responders, 53% reported via web, 0.7% via mobile only, and 43% via both. Older, black, and unemployed MO patients were more likely to report via web only. Of 3781 SUR responders, 55% reported via web, 0.3% via mobile only, and 45% via both. Older and unemployed SUR patients were more likely to report via web only; disabled SUR patients were less likely to use web only. Patients utilizing both modalities reported significantly more moderate-severe symptoms than web only responders [Table]. Conclusions: Very few patients reported via mobile only, which was unexpected in the context of trends toward mobile-based patient engagement. Moderate-severe symptoms were reported more frequently by dual-modality responders. Patients with access to both modalities may be more likely to report symptoms in real-time compared to web-users who may delay reporting until they have access to a device. The resulting difference between web and mobile reporting modalities could be due to age, race, and employment; future studies should assess other factors, such as locality and cellular coverage. This work emphasizes the importance of deploying ePROs via multiple modalities to maximize accessibility and response rates. Clinical trial information: NCT03850912. [Table: see text]

34 Background: Cancer survivors have complex medical and psychosocial needs and report difficulty accessing specialty care for short and long-term effects of treatment. We created an innovative multi-specialty survivorship clinic to address the medical and psychosocial consequences of cancer and to promote wellness and healthy lifestyle changes. Methods: The “Oncology, Wellness, Lifestyle and Survivorship” (OWLS) clinic was implemented 12/2020 for breast and gyn cancer survivors and extended to all cancer types in 111/2021. Patients complete pre and post-clinic survey to their medical and psychosocial concerns. OWLS is led by an internist and NP expert in survivorship with nurse navigator, physical activity coach, massage therapist on-site. A multidisciplinary team of providers experienced in survivorship care from hem/onc, cardiology, pulmonary, rheumatology, nephrology, dermatology, endocrinology, neurology, psychiatry, sexual health, physical therapy, nutrition, and lifestyle medicine meet monthly to create a comprehensive care management plan presented to survivors at their follow up visit and shared with their PCP and oncologist. Results: The OWLS team has seen 91 patients as of May 2022 and had 12 MDC meetings. Mean survivor age was 50 and the majority were white (80%) had breast cancer(76%) with non-metastatic disease 80%. Most frequent referrals were nutrition, physical therapy, gastroenterology and sexual health. At 6 mos f/u survey almost all were v.satisfied/satisfied with care. All OWLS MDC providers rated it as valuable. Conclusions: The OWLS clinic is an innovate, multi-specialty program that provides a comprehensive survivorship plan for cancer survivors at any stage of their disease. Areas for future growth include extending onsite services, expanding the number of male survivors serviced, and increasing outreach to non-white, non-commercially insured patients.[Table: see text]

242 Background: Among cancer patients (pts) treated with chemotherapy, electronic patient reported outcome (ePRO)-based symptom management programs at quaternary cancer care institutions have improved outcomes. Uptake of ePRO programs in the real-world setting, where less is known about severe symptom reporting, is often complicated by perceptions of increased workload and erroneous severe symptom reporting. The SIMPRO study group, which includes 6 diverse health systems, are implementing an integrated electronic symptom management (eSyM) program to address these challenges. Methods: SIMPRO sites deployed the Epic-embedded eSyM program for thoracic (THOR), gastrointestinal (GI), and gynecologic (GYN) medical oncology (MO) pts, who received PRO-CTCAE-based questionnaires via the patient portal twice weekly for 6 months after starting a new chemotherapy regimen. Symptoms were scored 0 (none), 1 (mild), 2 (moderate), and 3 (severe) and automatically transmitted to care teams within Epic. The distribution and predictors of severe symptom reporting were assessed using descriptive statistics and logistic regression modeling. Results: From September 2019 – March 2022, 47% of eligible pts (2679/5716) submitted 27,062 questionnaires (median age of 67 years, 55% female, 78% white, 53% married, and 49% retired). 17% of eSyM questionnaires included at least 1 severe symptom (15% for GI, 14% for GYN, and 18% for THOR). Table displays the frequencies of all symptoms reported with fatigue, general pain, and constipation being most common. Among respondents, older, black, and employed pts reported significantly fewer severe symptoms (p < 0.03); cancer type was not associated with a greater likelihood of severe symptom reporting. Conclusions: Only approximately 1 of every 6 eSyM responses included a severe symptom, suggesting that routine monitoring in the real-world could help identify patients experiencing bothersome symptoms with minimal disruption to clinical workload. The mix of symptoms commonly reported as severe are challenging to treat with medications alone, arguing that symptom management strategies should provide multidisciplinary supportive care. Interventions that aide both patients and care teams and are embedded within eSyM or Epic could help address these symptoms without overburdening care teams. Clinical trial information: NCT03850912. [Table: see text]

Highlights • Extrapulmonary lymphangioleiomyomatosis is rare and can be associated with tuberous sclerosis. • Recognition of lymphangioleiomyomatosis is important for early disease screening and genetic testing. • Lymphangioleiomyomatosis in lower uterine segment is very rare and can be overlooked.

Survival outcomes in ovarian cancer are poor. The aims of this Phase I progressive design study (NCT02903771) were to evaluate the maximum tolerated dose (MTD), tolerability, and antitumor activity of Cantrixil—a novel third-generation benzopyran molecule—in patients (n = 25) with advanced, recurrent/persistent epithelial ovarian, primary peritoneal, or fallopian tube cancer. All had completed ≥ 2 prior regimens, 3 (12%) had platinum-refractory disease, and 17 (68%) had platinum-resistant disease. Following intraperitoneal (IP) port placement, patients received weekly IP Cantrixil in 3-week cycles as monotherapy (Cycles 1–2), and then in combination with intravenous (IV) chemotherapy (Cycles 3–8). Part A (dose escalation) enrolled 11 patients in 6 dose-level cohorts. An MTD of 5 mg/kg was established with dose-limiting toxicity of ileus. Most treatment-related adverse events were gastrointestinal. Across Parts A and B (dose expansion), 16 (64%) patients received ≥ 1 3-week Cantrixil cycle, and had ≥ 1 post-baseline efficacy measurement available. The results show promising anti-tumor activity in monotherapy (stable disease rate of 56%) and in combination with IV chemotherapy (objective response rate of 19%, disease control rate of 56%, and median progression-free survival of 13.1 weeks). The molecular target and mechanism of action of Cantrixil are yet to be confirmed. Preliminary analysis of stem cell markers suggests that IP Cantrixil might induce ovarian cancer stem cell death and sensitize cells to standard chemotherapy, warranting further evaluation.

Gynecologic clear cell carcinoma is a rare histology, accounting for ~5% of all ovarian and endometrial cancers in the United States. Compared to other types of gynecologic cancer, they are generally less responsive to standard therapy and have an overall worse prognosis. In addition, mounting evidence suggests that the landscape of genetic and molecular abnormalities observed in these tumors is distinct from other cancers that arise from the same sites of origin. On a molecular level, these tumors characteristically display upregulation of the PI3K-AKT-mTOR and RAS-RAF-MAPK signaling axes, frequent loss of ARID1a, and overexpression of MDM2. Evidence also suggests that these tumors are more likely to express programmed death ligand 1 or demonstrate microsatellite instability than other gynecologic cancers. Despite these important differences, there has been relatively little investigation into histology-specific treatment of clear cell gynecologic cancers, representing an opportunity for new drug development. In this article, we review the unique genetic and molecular features of gynecologic clear cell cancers with an emphasis on potential therapeutic targets. The results of completed studies of treatment for clear cell carcinoma are also presented. We conclude with a discussion of ongoing clinical trials and potential avenues for future study.

A diagnosis of breast cancer (BC) can result in multifactorial stress. If not addressed, distress can have a negative impact on outcomes. The experience of patients with newly diagnosed BC has not been sufficiently investigated. This study characterizes distress among new patients in a multidisciplinary care (MDC) clinic. The study aimed to determine the degree of distress at presentation, to characterize the sources, and to evaluate the impact of an MDC visit. A retrospective review was performed from January 2015 to November 2017. Charts were accessed for demographics, tumor characteristics, and treatment data. Distress scores (DS) and problems as captured using the National Comprehensive Cancer Network (NCCN) Distress Thermometer were completed before evaluation and in a subgroup after an MDC visit. Predictors of severe distress (DS ≥4) were investigated using multivariable logistic regression. The paired t test was used to determine the impact of an MDC visit. The mean initial DS (n = 474) was 4.98. The top four sources of distress were worry, anxiety, fears, and sadness. Age younger than 65 years was significantly associated with a higher DS at presentation (p

Definitive chemoradiation (CRT) results in high cure rates of anal cancer, with advanced radiation (RT) techniques improving toxicity. However, there is limited data regarding these patients’ sexual function (SF), quality of life (QOL), and mood. We hypothesized that anal cancer treatment would result in detrimental effects on SF, QOL, and mood. We prospectively surveyed patients with anal cancer treated with definitive CRT. We assessed SF for women with the Female Sexual Function Index (FSFI) and for men with the International Index of Erectile Function (IIEF). For all patients, we assessed QOL using EORTC QLQ-C30 and CR29 and mood using the Hospital Anxiety and Depression Scale (HADS). We reported descriptive statistics for SF, QOL, and mood and used univariate analysis to evaluate predictors of SF for women. Of 50 eligible patients, 84% completed the surveys. Median time from RT until survey was 36 months (1–97 months). Women (n = 34) reported poor SF overall (mean FSFI score = 15, scale 2–36, standard deviation (SD) 10.4). Most women reported poor SF related to satisfaction, desire, orgasm, arousal, pain, and lubrication. Men (n = 8) also had poor overall satisfaction (mean IIEF score = 6.1, scale 2–10, SD 3.6). Men reported poor erectile function and lower satisfaction with intercourse. Mean QLQ-C30 QOL score was 86.5 (SD 16.3). Results from EORTC QLQ-CR-20 demonstrated patients experienced poor sexual interest. Per HADS, 2.5% reported depression and 18% anxiety. Patients with anal cancer experience sexual dysfunction after RT, with QOL and mood symptoms similar to patients with other cancers. Our data support the need for ongoing efforts to understand and address issues with SF, QOL, and mood following RT for these patients.

Hepatic angiosarcoma (HAS) is a rare and highly lethal malignancy with few effective systemic treatments. Relatively little is known about the genetic abnormalities that drive this disease. As a result, there has been minimal progress towards applying targeted therapies to the treatment of HAS. We describe the first reported case of a patient with HAS that harbored a fusion of ROS1 with GOPC/FIG. Similar to other rearrangements involving ROS1, the resulting fusion protein is believed to act as a major driver of carcinogenesis and may be subject to inhibition by drugs that target ROS1 such as crizotinib. We then queried the MSK-IMPACT clinical sequencing cohort and cBioportal datasets, demonstrating the previously unknown prevalence of ROS1-GOPC fusions in soft tissue sarcomas and hepatobiliary cancers. Amplification of these genes was also found to correlate with reduced overall survival. This is followed by a review of the role played by ROS1 rearrangements in cancer, as well as the evidence supporting the use of targeted therapies against the resulting fusion protein. We suggest that testing for ROS1 fusion and, if positive, treatment with a targeted therapy could be considered at the time of diagnosis for patients with angiosarcoma. This report also highlights the need for further investigation into the molecular pathophysiology of this deadly disease.

11551 Background: Immune checkpoint inhibitors (ICI) have limited efficacy for most sarcomas. Yet, responses are seen in particular sarcoma subtypes, highlighting the need for better predictive biomarkers. The T cell inflamed score (TIS), a gene expression signature reflective of an active tumor immune microenvironment, is associated with ICI response in multiple solid tumors. We evaluated the TIS across a large database of sarcomas to identify which histologic subtypes may benefit from ICI. Methods: Next generation sequencing of DNA (592 gene or whole exome)/RNA (whole transcriptome) was performed for 3605 sarcoma patient samples, representing 45 histologic subtypes (Caris Life Sciences, Phoenix, AZ). TIS (18 gene weighted coefficient composite value; Cristescu 2018) was calculated and the Microenvironment Cell Populations-counter tool (Becht 2016) was used to quantify immune cell populations. Results were compared to melanoma (n = 1255), a representative immunogenic tumor type. High TIS was defined as a score within the upper quartile of melanoma TIS (> 5.5). Percentage with high TIS are reported with 95% CI. Results: Median TIS was highest in inflammatory myofibroblastic tumor (IMT), epithelioid sarcoma (EPIS), myxofibrosarcoma (MFS), well differentiated liposarcoma, and solitary fibrous tumor (SFT). These did not differ significantly from melanoma (p > 0.06). Median TIS was lowest in embryonal rhabdomyosarcoma, desmoid tumor (DES), synovial sarcoma (SYNS), and Ewing sarcoma (ES). Histologic subtypes where > 10% of samples had a high TIS included IMT (29.9% ± 21.7%), MFS (23.3% ± 12.6%), pleomorphic sarcoma (PLSARC) (21.9% ± 5.8%), cutaneous angiosarcoma (ANGS) (18.4% ± 13.9%), spindle cell sarcoma (17.5% ± 7.6%), liposarcoma (LPS) (17% ± 10.7%), EPIS (15.4% ± 19.6%), visceral ANGS (13.2% ± 10.7%), pleomorphic LPS (13.6% ± 14.3%), fibrosarcoma (12.5% ± 13.2%), leiomyosarcoma (11.6%± 3.4%), malignant peripheral nerve sheath tumor (MPNST) (10.2% ± 7.7%), and perivascular epithelioid cell tumor (PEComa) (10% ± 10.7%). The relative abundance of immune and stromal cell populations was highly variable across sarcoma subtypes, yet a strong positive correlation between TIS and immune cell populations was observed for most subtypes (e.g. T cells, Spearman R range: 0.56 [P = 0.08] - 0.96 [P < 0.0001]). A notable exception was SFT, which had a relatively high median TIS but low abundance of CD8+ T cells and B cells. Conclusions: We found high median TIS and/or significant proportions of samples with a high TIS in sarcoma subtypes with previously demonstrated responsiveness to ICI, including MFS, PLSARC, LPS, and ANGS, while unresponsive tumor types such as RMS, DES, SYNS, and ES had low TIS. We further identified subtypes with high TIS but limited prior clinical data supporting ICI use, such as IMT, EPIS, MPNST, SFT, and PEComa. Our results warrant prospective exploration of TIS as a predictive biomarker for ICI use in sarcoma.

5598 Background: Clear Cell Carcinoma (CCC) outside the kidney is a rare tumor that can arise from multiple organs, including the ovary, endometrium and cervix. Extra-renal CCC is chemoresistant and has a poor prognosis. Data suggest that CCC of the gynecologic tract resembles the genomic profile of Renal Cell Carcinoma (RCC), which is responsive to immune checkpoint inhibition (ICI) therapy. We are conducting a two-stage phase 2 trial evaluating immunotherapy for extra-renal CCC. The primary objective is to assess overall rate of response (ORR); Progression-Free (PFS), Overall Survival (OS), and correlative biomarker studies are secondary. Here we present the results of Stage 1. Methods: This is a randomized two-stage non-comparative phase II study evaluating nivolumab (240mg IV every two weeks) alone (N) and in combination with ipilimumab (1mg/kg every six weeks, [N+I]) in patients with relapsed extra-renal CCC after at least one prior chemotherapy (no prior ICI), and measurable disease. Treatment was continued until disease progression or unacceptable toxicity. Stage 1 of this trial called for up to 30 volunteers (15 per arm) after which the study was closed. Consideration to reopen to stage 2 called for two or more responses in either arm. Here we present the completion of Stage 1; the release of results was approved by Brown University Oncology Group (BrUOG) Data Safety and Monitoring Committee. Results: Between July 2018 and October 2021, 30 patients were enrolled and 29 were treated (Table). The majority (83%) had CCC of the ovary (n=24). The ORR with N and N+I was 14.2 and 26.7%, respectively. The 6 month PFS rate was 19.1 and 43.8%; median PFS was 2.7 (95%CI 1.3-5.1) and 5.1 months (95%CI 0.9-NR), respectively. Grade ≥3 treatment-related toxicities occurred in 4 (28.6%) on N and 5 (33.3%) on N+I. There were no treatment-related deaths and no new safety signals. One volunteer enrolled on N+I stopped treatment after two years and remains in CR to date. Conclusions: Although sufficient activity was seen in CCC in both arms, the single-agent activity of N is similar to published reports in platinum-resistant epithelial ovarian cancer and decision made not to pursue it further. However, the combination of ipilimumab and nivolumab warrants additional investigation, and the second stage of this study will enroll 14 more patients to receive N+I. Clinical trial information: NCT03355976. [Table: see text]

2630 Background: MDM2/MDM4 are implicated in hyperprogression after immune checkpoint blockade (ICB). Our preclinical studies showed reduced T-cell killing of MDM2-amplified tumor cells that was overcome by an MDM2 antagonist or gene knockdown, and we observed additional tumor killing by T-cells with MDM2 inhibition plus anti-PD1. We hypothesized that MDM2/4 gene amplification/overexpression correlates with resistance to ICB and investigated the association of MDM2/4 alterations to overall survival (OS) following ICB across multiple solid tumors. Methods: Solid tumors tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing on DNA (NGS) were analyzed. MDM2/4 amplification (amp) was tested by NGS and determined as either amp4 (cutoff of >=4.0 copies) or amp6 (>=6.0) or amp8 (>=8.0). Real-world OS was obtained from insurance claims data and calculated from treatment start or tissue collection to last contact. Kaplan-Meier estimates were calculated for molecularly defined groups. X2/Fisher-Exact were used and significance determined as P-value adjusted for multiple comparisons (q