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Background: Fatigue often interferes with functioning in patients with advanced cancer, resulting in increased family caregiver burden. Acceptance and commitment therapy, a promising intervention for cancer-related suffering, has rarely been applied to dyads coping with advanced cancer. Aim: To examine the feasibility, acceptability, and preliminary efficacy of acceptance and commitment therapy for patient-caregiver dyads coping with advanced gastrointestinal cancer. Primary outcomes were patient fatigue interference and caregiver burden. Design: In this pilot trial, dyads were randomized to six weekly sessions of telephone-delivered acceptance and commitment therapy or education/support, an attention control. Outcomes were assessed at baseline and at 2 weeks and 3 months post-intervention. Setting/participants: Forty patients with stage III–IV gastrointestinal cancer and fatigue interference and family caregivers with burden or distress were recruited from two oncology clinics and randomized. Results: The eligibility screening rate (54%) and retention rate (81% at 2 weeks post-intervention) demonstrated feasibility. At 2 weeks post-intervention, acceptance and commitment therapy participants reported high intervention helpfulness (mean = 4.25/5.00). Group differences in outcomes were not statistically significant. However, when examining within-group change, acceptance and commitment therapy patients showed moderate decline in fatigue interference at both follow-ups, whereas education/support patients did not show improvement at either follow-up. Acceptance and commitment therapy caregivers showed medium decline in burden at 2 weeks that was not sustained at 3 months, whereas education/support caregivers showed little change in burden. Conclusions: Acceptance and commitment therapy showed strong feasibility, acceptability, and promise and warrants further testing. Trial Registration: ClinicalTrials.gov NCT04010227. Registered 8 July 2019, https://clinicaltrials.gov/ct2/show/NCT04010227?term=catherine+mosher&draw=2&rank=1

Despite improved treatment strategies for multiple myeloma (MM), patient outcomes in low- and middle-income countries remain poor, unlike high-income countries. Scarcity of specialized human resources and diagnostic, treatment, and survivorship infrastructure are some of the barriers that patients with MM, clinicians, and policymakers have to overcome in the former setting. To improve outcomes of patients with MM in Western Kenya, the Academic Model Providing Access to Healthcare (AMPATH) MM Program was set up in 2012. In this article, the program's activities, challenges, and future plans are described distilling important lessons that can be replicated in similar settings. Through the program, training on diagnosis and treatment of MM was offered to healthcare professionals from 35 peripheral health facilities across Western Kenya in 2018 and 2019. Access to antimyeloma drugs including novel agents was secured, and pharmacovigilance systems were developed. Finally, patients were supported to obtain health insurance in addition to receiving peer support through participation in support group meetings. This article provides an implementation blueprint for similar initiatives aimed at increasing access to care for patients with MM in underserved areas.

PURPOSETreatment patterns and survival outcomes of patients with multiple myeloma (MM) in Kenya have not been adequately characterized. The objectives of this study were to describe the clinical, laboratory, and imaging findings at diagnosis, to describe the treatment offered, and to determine the survival outcomes of patients with MM over an 11-year period.PATIENTS AND METHODSA retrospective chart review was carried out for all patients who were diagnosed and treated for MM at Moi Teaching and Referral Hospital from 2009 to 2019. The Kaplan-Meier method was used to estimate survival. Factors affecting survival were identified using univariate and multivariate analyses.RESULTSA total of 221 patient charts were analyzed of which 124 belonged to male patients (56.1%). The median age at diagnosis was 61 years. Bone pain was the most common presenting complaint observed in 69.6% of 194 patients assessed. Out of 102 patients who received imaging studies, 60 (58.8%) had lytic lesions, 30 (29.4%) had fractures, whereas 30 (29.4%) had spinal cord compression. Anemia, renal failure, and hypercalcemia were observed in 87/187 (46.5%), 22/161 (13.7%), and 23/42 (54.8%) patients, respectively. Thalidomide and dexamethasone (65.2%); bortezomib, thalidomide, and dexamethasone (14.6%); and melphalan and prednisolone (11.9%) were the most prescribed initial chemotherapy regimens among 219 patients analyzed. Overall survival at 1 and 5 years was 70% and 21%, respectively; median overall survival was 29.0 months. In multivariate analysis, male sex (hazard ratio [HR] 1.9), baseline anemia (HR 1.8), and baseline renal failure (HR 3.2) were associated with significantly shorter survival.CONCLUSIONSurvival outcomes were poor despite increased use of multiagent-based chemotherapy regimens. Greater access to available diagnostics and treatments is required to achieve rational treatment and increased survival.

BACKGROUND Despite favorable clinical outcomes, a subset of patients with thymic epithelial tumors (TETs) develop metastasis. The Cancer Genome Atlas (TCGA) provides genomic data on primary TETs (pTETs). This study assessed the molecular alterations and uncovered targetable pathways in metastatic TETs (mTETs). METHODS From 2015 to 2020, 49 patients with stage IV TETs underwent Clinical Laboratory Improvement Amendments–based sequencing using whole-exome sequencing (n = 33), panel-based testing (n = 12), and/or liquid biopsy (n = 24). Specimens were obtained from a metastatic organ (n = 36) or relapsed primary mediastinal mass (n = 10), whereas four patients underwent a liquid biopsy only. Data on pTETs were derived from the TCGA. RESULTS Compared with the pTET data set, patients with mTETs were younger (54 years v 60.5 years, P = .009) and had more aggressive histologies, with the most common tumor type being thymic carcinoma (n = 22, 40.7%) and B3 thymoma (n = 15, 27.8%). GTF2I was the most altered gene in primary thymomas (48.80%, n = 60). In metastatic thymoma and thymic carcinoma, TP53 was the most common genetic alteration (31% and 36%, respectively). In mTETs, the genomic alteration occurred in the TP53/CDK, EGFR/RAS, and PI3K/mTOR pathways. Biopsies obtained from distant metastasis were more commonly found to contain targetable mutations. There was an overlap of 61% (22 of 36) between tissue and liquid biopsy genomic alterations. CONCLUSION Clinically actionable genomic alterations are frequently observed in mTETs, indicating a value of repeat biopsy (preferably from a metastatic site of TETs for sequencing at the time of recurrence (TCGA data).

Background and Hypothesis:Thymic Epithelial Tumors are uncommon tumors of the anterior mediastinum composed ofthymomas and thymic carcinomas (TC). TC’s are known to have worse disease outcomes andlower rates of survival in comparison to thymomas and are suspected to have lower responserates to chemotherapy as well. As these tumors are rare, little data exists assessing the trueefficacy of chemotherapeutic regimens for TC patients. Due to this lack of data, and that theIndiana University Health Simon Cancer Center treats a high percentage of TET patients, adatabase of these patients covering a variety different disease characteristics and treatmentshas been established. We hypothesize, upon evaluation of this database, response rates toanthracycline based regimens (PAC) will be superior to non-anthracycline based regimens (i.e.,PE, Carbo/Taxol) for TC patients. Methods:In this project, a collection of patients seen by Dr. Patrick Loehrer and/or Dr. Kenneth Keslerwas acquired, and a database was created using these patients in RedCap. Once established,we evaluated patient medical records in Cerner and entered data related to diseasecharacteristics and treatments. These patients were then analyzed accordingly to evaluatechemotherapy response rates. Results:The database yielded 123 instances of chemotherapy treatment for TC. Of which, the mostpopular treatments were PAC and Carbo/Taxol. The data suggests that PAC generates a higherresponse rate (65.5%) than other therapies (Carbo/Taxol: 27.6%, PE: 58.3%, etc.). Therefore,there is evidence that anthracycline based regimens may be more effective at generatingresponse rates in comparison to non-anthracycline based regimens. Conclusion and Potential Impact:This project will help elucidate the effectiveness of recommended systemic therapies for thymiccarcinoma patients from one of the largest TET databases constructed. Ultimately, we hope thatwith clarity of the effectiveness of treatment, this can serve as a reliable reference for evidencebasedmedicine for the care of TC patients.

Background and Objective:Thymic epithelial tumors (TETs) include thymic carcinomas and thymomas, the latter of which can be further categorized by the World Health Organization (WHO) histologic classification based on the morphology of epithelial cells and the ratio of lymphocyte to epithelial cells. TETs are rare malignancies with an incidence of 0.15 per 100,000 in the United States. While their etiologies remain unknown, these tumors are associated with distinctly high rates of autoimmune disorders and paraneoplastic syndromes. Approximately 30% of patients with thymoma also carry a diagnosis of myasthenia gravis (MG). For the present retrospective study, we created a database of patients with TETs and examined prevalence of each histologic subtype in patients with MG. Methods:Drs. Patrick Loehrer, Kenneth Kesler, and colleagues have collaborated at the Indiana University Simon Comprehensive Cancer Center to care for over 1000 patients with TETs. The electronic health records of these patients were accessed via Cerner and used to input demographic, diagnostic, and histologic data into a REDCap database. These tumors were further categorized by WHO classification, and those comprising multiple histologic types were included separately in each subgroup. Results:Of 626 patients deemed to have sufficient documented histologic and diagnostic data, 110 had both MG and a TET diagnosis confirmed by pathology report. The greatest prevalence of WHO histologic type in patients with thymoma and MG was Type B2 (47), followed by Type B3 (34), Type B1 (22), Type A (9), Type AB (7), and unspecified thymoma (7). Notably, only 3 of 159 (1.87%) total patients with thymic carcinoma had comorbid MG in contrast to 107 of 467 (22.91%) patients with thymoma and MG; this suggests a uniquely favorable microenvironment of thymoma in patients with MG. Clinical Impact and Implications:Future work will aim to determine whether histologic classification has a predictive value for tumor prognosis in patients with and without MG. Furthermore, patterns of gene expression associated with thymoma in patients with and without MG may elucidate the etiologic mechanisms for the development of this autoimmune disorder.

Background: Thymic epithelial tumors (TET’s), including thymomas (5 histological subtypes) and thymic carcinomas, are rare tumors with an estimated incidence of 0.15 per 100,000 person-years in the United States. While their etiologies remain largely unknown, some are associated with uniquely high rates of paraneoplastic syndromes and an elevated risk of secondary malignancies. And, though thymomas were once thought to be benign tumors, it is now well-documented that all TET's can metastasize. The gold-standard in TET staging, the Masaoka-Koga system, defines metastatic disease as Stage IV, further specifying pleural/pericardial metastases as Stage IVa and lymphogenous/hematogenous metastases as IVb. Unfortunately, little is known about patient prognosis as it relates to metastasis location. Here, we assemble and analyze one of the largest single-institution databases of TET patients in the world and seek to examine trends in metastases and their correlation with patient prognosis. Methods: Files of 1023 TET patients seen at Indiana University Hospital were accessed via Cerner, after which a standardized information list including demographics, diagnostics, tumor histology, treatments used, disease course, and patient outcome at last follow-up was extracted and input into a RedCap database. Results: Stage IV disease cases were filtered, yielding a total of 428 patients. Of these patients, 122 (29%) had carcinoma, making carcinoma the single largest histology represented in Stage IV. Locations of metastases also varied, with 284 patients (66%) having pleural metastases, 171 (40%) having lung, 71 (17%) liver, 58 (14%) bone, 56 (13%) pericardium, 37 (9%) neck lymph nodes, 12 (3%) brain, and 5 (1%) kidney. Moreover, 98 (23%) patients presented in stage IVb without any pleural/pericardial metastases. At last follow-up, 10% (19) of Stage IVa patients had no recurrence compared to only 3% (7) of IVb patients. Potential Impact: These data altogether suggest that disease spread outside the thorax occurs much more commonly than previously reported, and that rates of metastasis vary with tumor histology. Future analysis will elucidate the exact differences in the patterns of spread among histological types, how these patterns correlate with prognosis, and the implications of this on screening and treatment options.

Objective: A longitudinal study was conducted among women living with HIV in Kenya to determine if duration of anti-retroviral (ART) usage altered detection and persistence of oncogenic (high-risk) human papillomaviruses (HR-HPV). Methods: Women living with HIV without cervical dysplasia were enrolled at a cervical cancer screening clinic. Three cervical swabs, HIV viral loads, and CD4 cell counts were obtained at enrollment and at two annual visits. HPV genotyping was performed on swabs (Roche Linear Array). Linear regression models assessed effects of ART duration on HR-HPV detection and persistence. Results: Seventy-seven women, median age 38 years, completed three study visits and were included in the analysis. The mean time from HIV diagnosis to enrollment was 9.6 years (SD 3.9 years). The mean ART duration was 6.2 years (SD 3.1 years). Most women had undetectable HIV viral loads and CD4 cell counts above 500 cells/L. Each additional year of ART use reduced the likelihood of detection of HR-HPV by 10–15% and persistent detection of A9 HR-HPV by 20%. Conclusion: Among Kenyan women living with HIV, longer duration of ART use was associated with significantly reduced risk of all detection and persistent detection of HR-HPV.

Background: Cancer care coordination across major academic medical centers and their networks is evolving rapidly, but the spectrum of organizational efforts has not been described. We conducted a mixed-methods survey of leading cancer centers and their networks to document care coordination and identify opportunities to improve geographically dispersed care. Methods: A mixed-methods survey was sent to 91 cancer centers in the United States and Canada. We analyzed the number and locations of network sites; access to electronic medical records (EMRs); clinical research support and participation at networks; use of patient navigators, care paths, and quality measures; and physician workforce. Responses were collected via Qualtrics software between September 2017 and December 2018. Results: Of the 69 responding cancer centers, 74% were NCI-designated. Eighty-seven percent of respondents were part of a matrix health system, and 13% were freestanding. Fifty-six reported having network sites. Forty-three respondents use navigators for disease-specific populations, and 24 use them for all patients. Thirty-five respondents use ≥1 types of care path. Fifty-seven percent of networks had complete, integrated access to their main center’s EMRs. Thirty-nine respondents said the main center provides funding for clinical research at networks, with 22 reporting the main center provides all funding. Thirty-five said the main center provided pharmacy support at the networks, with 15 indicating the main center provides 100% pharmacy support. Certification program participation varied extensively across networks. Conclusions: The data show academic cancer centers have extensive involvement in network cancer care, often extending into rural communities. Coordinating care through improved clinical trial access and greater use of patient navigation, care paths, coordinated EMRs, and quality measures is likely to improve patient outcomes. Although it is premature to draw firm conclusions, the survey results are appropriate for mapping next steps and data queries.

In recognition of the rising incidence and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has prioritized efforts to enhance its engagement at a global level. Among the recommendations included in the 2016 Global Oncology Leadership Task Force report to the ASCO Board of Directors was that ASCO should promote the recognition of global oncology as an academic field. The report suggested that ASCO could serve a role in transitioning global oncology from an informal field of largely voluntary activities to a more formal discipline with strong research and well-defined training components. As a result of this recommendation, in 2017, ASCO formed the Academic Global Oncology Task Force (AGOTF) to guide ASCO’s contributions toward formalizing the field of global oncology. The AGOTF was asked to collect and analyze key issues and barriers toward the recognition of global oncology as an academic discipline, with an emphasis on training, research, and career pathways, and produce a set of recommendations for ASCO action. The outcome of the AGOTF was the development of recommendations designed to advance the status of global oncology as an academic discipline.

PurposeTo investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas.MethodsThis was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective response rate (complete response [CR] + partial response [PR]). Secondary endpoints included toxicity; progression free survival (PFS); overall survival (OS); disease control rate (DCR), i.e., the percentage of patients who achieve either PR or CR or stable disease [SD] for at least 4 months.ResultsBetween 10/13/2014 and 1/18/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23–74). 71% were females and 71% white. All patients had WHO B2 (29%) or B3 (71%) thymoma. Patients received buparlisib for a median of 4.5m (2–33). At a median follow up of 16.6m (2.4–31.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 – 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7–31.3). Most common grade 3-4 adverse events related to buparlisib were dyspnea (21%), rash (14%), elevated transaminases (14%), cough (7%), pneumonitis (7%), anxiety (7%), fatigue (7%) and hyperglycemia (7%). Reasons for treatment discontinuation included progression of disease (n= 5), rash (n=4), pulmonary toxicity (n=3), sinusitis (n=1), and disseminated toxoplasmosis plus autoimmune cholangitis (n=1). As of 3/2021, 8 patients have died, 7 due to disease progression and 1 due to central nervous system toxoplasmosis and autoimmune cholangitis.ConclusionBuparlisib showed modest activity in patients with relapsed or refractory thymomas. Further investigation of PI3K pathway targeted therapy in thymoma is warranted. (clinicaltrials.gov ID: NCT02220855).Clinical trial registrationclinicaltrials.gov, identifier (NCT02220855)

731 Background: The incidence of PDAC is on the rise and it is predicted to be the 2nd leading cause of cancer related mortality in the next decade. Most patients present with advanced disease at diagnoses with limited systemic treatment options. Fluoropyrimidines are active in PDAC. Lonsurf (L) is an orally administered combination of a thymidine-based nucleic acid analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil hydrochloride. Preclinical data demonstrate Lonsurf may have activity in 5-FU resistant malignancies. This phase I study combines Gem, nab-P, and L. Methods: Gem and nab-P are dosed on days 1 and 15 IV on a 28 day cycle. L (20-30mg/m2) is dosed twice daily on days 2-6 and 16-20 (table 1). Dose escalation is by 3+3 design. Key eligibility include pts with untreated locally advanced or metastatic PDAC, ECOG 0-1, and adequate hepatic and bone marrow function. Results: 14 pts (median age 62 yrs [range 43-74]) have been enrolled. Dose was initiated at DL1. The first 3 pts were treated without DLT. DL2 exceeded the MTD with 1 patient experiencing grade 3 infection (cholangitis). Dose expansion to 7 patients was completed at DL 1 with no further DLTs. The RP2D is Gem 800mg/m2, Nab-P 100mg/m2, and L 25mg/m2. Of the 10 patients with evaluable disease, 2 (20%) had PR and 7 (70%) had SD. Pts were on study a median of 14 months (range 4 -31+). Most common grade 3/4 AEs include fatigue (46%,) neutropenia (38%), anemia (31%) anorexia (15%), nausea (15%), vomiting (15%), abdominal pain (15%), hyperglycemia (15%). No grade 5 events occurred. Conclusions: The RP2D is Gem 800mg/m2, Nab-P 100mg/m2, and L 25mg/m2. This combination was well tolerated with expected toxicities of myelosuppression with prolonged responses seen. Clinical trial information: NCT04046887 . [Table: see text]

Objectives There are limited treatment options for patients with thymic malignancies. Here we present data supporting treatment with single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor. Materials and methods This was a phase 2 open-label, single arm trial of amrubicin in patients with thymoma (T) or thymic carcinoma (TC), conducted at two academic institutions. Patients were included if they had received at least one prior chemotherapy regimen. The first 18 patients received amrubicin at 40 mg/m2 IV days 1–3 repeated every 3-weeks. Due to the high incidence of febrile neutropenia, dosing was subsequently amended to 35 mg/m2 for the final 15 patients. Results A total of 33 patients (14 T/19 TC) were enrolled from 2011 to 2014. Median number of prior therapies was 2. Best response included 6 partial responses, 21 stable disease, and 6 progressive disease (all TC). Objective response rate was 18% (90% exact binomial CI 8.2%–32.8%; T = 4/14 (29%), TC = 2/19 (11%)). Median progression-free survival was 7.7 months (T: 8.3 months; TC: 7.3) and median overall survival was 29.7 months (T: 54.1 months; TC: 18 months). There was a high rate of febrile neutropenia (7 patients) that occurred despite a reduction in amrubicin dose and one related death. Five patients had reduction in LVEF below 50% during the course of treatment resulting in treatment discontinuation in one patient. Conclusion Amrubicin shows promise as a single agent in heavily pre-treated patients with thymic malignancies. Notable side effects include febrile neutropenia and the use of growth factor support is essential. Further investigation of this agent is warranted.

Background Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women. Methods Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher’s exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software. Results Compared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007–1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1.206–8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764–0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565–0.883) were associated with reduced detection. Conclusion HIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.

Background Fatigue interference with activities, mood, and cognition is one of the most prevalent and bothersome concerns of advanced gastrointestinal (GI) cancer patients. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing responsibilities. Evidence-based interventions jointly addressing cancer patient fatigue interference and caregiver burden are lacking. In pilot studies, acceptance and commitment therapy (ACT) has shown promise for addressing symptom-related suffering in cancer patients. The current pilot trial seeks to test a novel, dyadic ACT intervention for both advanced GI cancer patients with moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden or distress. Methods A minimum of 40 patient-caregiver dyads will be randomly assigned to either the ACT intervention or an education/support control condition. Dyads in both conditions attend six weekly 50-min telephone sessions. Outcomes are assessed at baseline as well as 2 weeks and 3 months post-intervention. We will evaluate the feasibility, acceptability, and preliminary efficacy of ACT for improving patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities, psychological flexibility, and quality of life. We will also explore the effects of ACT on patient and caregiver physical and mental health service use. Discussion Findings will inform a large-scale trial of intervention efficacy. Results will also lay the groundwork for further novel applications of ACT to symptom interference with functioning and caregiver burden in advanced cancer. Trial Registration ClinicalTrials.gov, NCT04010227. Registered 8 July 2019.

e20625 Background: Thymoma is an uncommon malignancy often associated with paraneoplastic syndromes including pure red cell aplasia (PRCA), occurring in up to 5% of patients with thymoma. Considering the rarity of thymoma-associated PRCA, optimal treatment regimens and impact on thymoma disease course have yet to be established. Methods: A retrospective chart review was conducted for patients seen at the IUSCCC with thymoma and PRCA to extract and synthesize data on patient demographics, thymoma histology, hemoglobin levels, timeline of diagnoses, treatment regimens, and outcomes. Results: From 1993 to 2022, 10 patients (M:F = 4:6) with thymoma and PRCA were identified. Median follow-up duration was 75.0 months (range 32-202). Median age at thymoma diagnosis was 53.5 (range 40-80). Median age at PRCA diagnosis was 64.0 (range 40-80). Mean hemoglobin at PRCA diagnosis was 6.6. WHO classifications of thymoma included 10.0% A, 40.0% B1, 10.0% B2, 10.0% B2/B3, 30.0% not otherwise specified. Masoaka stages of thymoma included 20.0% stage I, 10.0% stage II, 10.0% stage III, 30.0% stage IVA, 30.0% stage IVB. Patients initially presented with thymoma (n = 7), PRCA (n = 1), or concurrent thymoma and PRCA (n = 2). For those initially presenting with thymoma, PRCA was subsequently diagnosed after a median 19.5 months (range 9-144). Of these 7 patients 3 experienced a relapse or progression of their thymoma at time of PRCA diagnosis, 3/7 had stable disease (1-insufficient data). Additional paraneoplastic syndromes were seen in 6 patients (hypogammaglobulinemia-2; pure white cell aplasia-1; myasthenia gravis-1; autoimmune neutropenia-1; colitis -1). Other diminished immunologic parameters observed were: immunoglobulin levels (n = 3); CD4 counts (n = 2); CD4:CD8 ratio (n = 4); and total B cell (n = 6). The primary outcome of the study was transfusion dependence, defined as requiring ≥1 PRBC transfusion per month for ≥3 months. Six achieved transfusion independence, while 3 remained transfusion dependent despite therapy (1 LTFU). Both patients with concurrent thymoma and PRCA underwent thymectomy, but only one achieved transfusion independence with additional adjuvant immunosuppressive therapies. Median duration of transfusion independence was 18.5 months (range 4-204). Median survival after bone marrow biopsy diagnosis of PRCA was 50.0 months (range 9-202). Conclusions: The impact of PRCA on thymoma disease course is variable. Most patients will recover with immunosuppressive therapy, but approximately 30.0% patients remained transfusion dependent. Our experience does not support thymectomy alone as primary treatment of PRCA. More research is needed to evaluate the mechanism of developing PRCA in thymoma and to define the optimal therapeutic approach.

11008 Background: By 2040, an estimated 69% of all cancer deaths globally will occur in LMICs. Recognizing this, ASCO formed the Academic Global Oncology Task Force in 2017 to help formalize the global oncology (GO) field. Their recommendations included: better engagement with the National Cancer Institute (NCI) Center for Global Health (CGH), increased funding, and development of forums to highlight global cancer research and control activities. To further clarify how GO programs are defined and to better understand the perspectives and needs of cancer research leaders, CGH conducted a survey of the 71 Directors at the NCI-Designated Cancer Centers (NDCC). Methods: A 19-question survey was designed using Microsoft Forms and sent to the NDCC Directors via email. Responses were collected from July to September 2021. Two coders reviewed the qualitative responses to categorize the data into thematic areas. Analyses were conducted in Microsoft Excel. Results: Seventy of 71 (99%) NDCC Directors responded to the survey. 41 NDCCs (59%) reported dedicated GO programs or plans to create such a program within 5 years. Additionally, 16 Directors reported GO activities without a dedicated program, while 13 reported no GO activities. The Directors described GO as having high/extremely high (39%) or moderate (50%) importance relative to other priorities, across all types of NDCCs (basic, clinical, or comprehensive). Eight NDCCs (11%) described GO as a low priority or non-priority. 31 NDCCs (44%) reported dedicated funding for GO activities. Directors estimated interest in GO to be higher among junior faculty and trainees than senior and mid-career faculty. Future goals for established or developing GO programs included: recruitment of leadership, formalizing a strategic vision, establishing partnerships, and increasing the number of activities with international collaborations. Barriers noted were limited funding, limited capacity and expertise, and prioritizing the needs in domestic NDCC catchment areas. Conclusions: Despite variation across NDCCs, GO interest is strong as expressed by Center Directors. Strategic planning, increased funding, and improved collaboration within and between NDCCs were reported as necessary to strengthen GO at NDCCs. Continued leadership from ASCO, the NCI, and other international organizations can help facilitate dialogue and increase the prioritization of GO activities at NDCCs.

e20623 Background: Thymomas are rare neoplasms in the anterior mediastinum that account for less than 1% of tumors. The presence of immune cells within the tumor is one of the cardinal features of thymomas. However, the nature of the immune infiltration is not well characterized. Methods: Deconvolution of the gene expression of thymomas in the TCGA-THYM cohort was performed using the CIBERSORT and xCELL programs. Pairwise correlative analyses were performed to study the relationships of cell types and thymoma histological subtypes. Results: The differences in presence of immune cells was better highlighted using xCELL, which identifies 67 categories of cells rather than in the 23 categories identified by CIBERSORT. As expected, there were dramatic differences in the presence of T-cells (almost all subtypes) and B-cells between A/AB and type B (-1, -2, -3) thymomas. A significant difference (P < 0.0001) in different type B thymomas was observed for the presence of monocytes, macrophages, and M1, but not in M2 macrophages. Significant differences in dendritic cells were observed within subtypes of B thymoma. Similarly, statistically significant differences were observed between most subtypes in Immunoscore (except AB/B3) and MicroenvironmentScore (except A/B3; AB/B2 and AB/B3). However, StromalScore differences were observed only in comparisons of type A/AB with B type thymomas (except AB/B3). Interestingly, there also differences in postulated pre-adipocytes, hepatocytes, mesangial cells and osteoblasts in types A vs B, and melanocytes between subtypes of B thymomas. Conclusions: The differences in lymphoid content of the tumor microenvironment is associated with dramatic changes in cell type distribution in subtypes of thymoma. These differences in composition underpin their clinicopathological behavior including incidence of myasthenia and likelihood of recurrence.

The coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic events have markedly changed the environment in which cancer clinical trials are conducted. These events have resulted in a substantial, immediate-term decrease in accrual to both diagnostic and therapeutic cancer investigations as well as substantive alterations in patterns of oncologic care. The sponsors of clinical trials, including the US National Cancer Institute, as well as the cancer centers and community oncology practices that conduct such studies, have all markedly adapted their models of care, usage of healthcare personnel, and regulatory requirements in the attempt to continue clinical cancer investigations while maintaining high levels of patient safety. In doing so, major changes in clinical trials practice have been embraced nationwide. There is a growing consensus that the regulatory and clinical research process alterations that have been adopted in response to the pandemic (such as the use of telemedicine visits to reduce patient travel requirements and the application of remote informed consent procedures) should be implemented long term. The COVID-19 outbreak has also refocused the oncologic clinical trials community on the need to bring clinical trials closer to patients by dramatically enhancing clinical trial access, especially for minority and underserved communities that have been disproportionately affected by the pandemic. In this commentary, changes to the program of clinical trials supported by the National Cancer Institute that could improve clinical trial availability, effectiveness, and diversity are proposed.

Objectives: Cervical cancer is caused by persistent infection with oncogenic, or “high-risk” types of human papillomaviruses, and is the most common malignancy in Kenyan women. A longitudinal study was initiated to investigate factors associated with persistent human papillomavirus detection among HIV-infected and HIV-uninfected Kenyan women without evidence of cervical dysplasia. Methods: Demographic/behavioral data and cervical swabs were collected from HIV-uninfected women (n = 82) and HIV-infected women (n = 101) at enrollment and annually for 2 years. Human papillomavirus typing was performed on swabs (Roche Linear Array). Logistic regression models of human papillomavirus persistence were adjusted for demographic and behavioral characteristics. Results: HIV-infected women were older and less likely to be married and to own a home and had more lifetime sexual partners than HIV-uninfected women. All HIV-infected women were receiving anti-retroviral therapy at enrollment and had satisfactory CD4 cell counts and HIV viral loads. One- and two-year persistent human papillomavirus detection was significantly associated with HIV infection for any human papillomavirus, high-risk human papillomavirus, International Agency for the Research on Cancer-classified high-risk human papillomavirus, and non-oncogenic “low-risk” human papillomavirus. Conclusion: Persistent detection of oncogenic and non-oncogenic human papillomavirus was strongly associated with HIV infection in Kenyan women with re-constituted immune systems based on satisfactory CD4 cell counts. In addition to HIV infection, factors associated with an increased risk of human papillomavirus persistence included a higher number of lifetime sex partners. Factors associated with decreased risk of human papillomavirus persistence included older age and being married. Further studies are needed to identify the immunological defects in HIV-infected women that allow human papillomavirus persistence, even in women receiving effective anti-retroviral therapy. Further studies are also needed to determine the significance of low-risk human papillomavirus persistence in HIV-infected women.

PURPOSE A postmarket evaluation of chemotherapy dosage forms in Ethiopia was conducted to test the accuracy of the chemoPAD, a paper analytical device for drug quality screening. MATERIALS AND METHODS In September of 2018 in Addis Ababa, Ethiopia, 41 anticancer drug dosage forms (representing 4 active ingredients, 5 brands, and 7 lot numbers) were collected and were rapidly screened for quality using a chemotherapy paper analytical device (chemoPAD). Confirmatory analysis via high performance liquid chromatography was conducted. RESULTS The chemoPAD showed that the correct active pharmaceutical ingredient was present in doxorubicin, methotrexate, and oxaliplatin injectable dosage forms. However, 11 of 20 cisplatin samples failed the screening test. Confirmatory assay by high-performance liquid chromatography showed that all 20 cisplatin samples—comprising three lot numbers of a product stated to be Cisteen—were substandard, containing on average 54% ± 6% of the stated cisplatin content. Inductively coupled plasma optical emission spectroscopy analysis of five representative samples found 57% to 71% of the platinum that should have been present. The sensitivity of the chemoPAD for detection of falsified products could not be measured (as none were present in these samples), but the selectivity was 100% (no false positives). The sensitivity for detection of substandard products was 55%, and the selectivity was 100% (no false positives). CONCLUSION Although instrumental analysis by pharmacopeia methods must remain the gold standard for assessing overall drug quality, these methods are time consuming and patients could be exposed to a bad-quality drug while clinical workers wait for testing to be performed. The chemoPAD technology could allow clinicians to check at the point of use for serious problems in the quality of chemotherapy drugs on a weekly or monthly schedule.

Purpose Kaposi’s sarcoma (KS) is a spindle cell tumor resulting from growth dysregulation in the setting of infection with human herpes virus-8 (also called KS herpes virus). Advanced KS is characterized by poor responses to antiretroviral therapy and some of the chemotherapy readily accessible to patients in low-resource areas. Gemcitabine induced partial and complete regression of AIDS-associated KS (AIDS-KS) in 11 of 24 patients in a pilot study. The current study compares the antimetabolite gemcitabine with the standard care bleomycin and vincristine (BV) in the treatment of chemotherapy-naïve patients with AIDS-KS in a resource-limited setting. Patients and Methods Patients with persistent or progressive KS despite treatment with combined antiretroviral therapy were randomly assigned to receive gemcitabine 1,000 mg/m2 or bleomycin 15 IU/ m2 and vincristine 1.4 mg/m2 given twice weekly. The main end point was objective response by bidirectional measurement, adverse events, and quality of life after three cycles of chemotherapy. Results Of 70 participants enrolled, 36 received gemcitabine and 34 received BV. Complete response was achieved in 12 patients (33.3%) in the gemcitabine arm and six (17.6%) in the BV arm ( P = .175). The partial response rate was 52.8% (n = 19) in the gemcitabine arm and 58.8% (n = 20) in the BV arm. Both study arms reported similar neurologic and hematologic adverse events; there was statistically significant baseline to post-treatment improvement in health-related quality-of-life scores. Conclusion The results of this randomized, phase IIA trial demonstrate gemcitabine activity in chemotherapy-naïve patients with AIDS-KS, on the basis of response rates, adverse events, and health-related quality-of-life scores.

Objective To assess the baseline types of HPV infection among HIV-positive and HIV-negative women in western Kenya undergoing cryotherapy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia. Methods A prospective observational study was conducted of baseline HPV characteristics of women undergoing visual inspection with acetic acid (VIA) and cryotherapy or LEEP. After a positive VIA in HIV-positive and HIV-negative women, data on demographics, CD4 count, and use of antiretroviral therapy and a cervical swab were collected. HPV typing was performed using the Roche Linear Array. Results Of 175 participants, 86 (49.1%) were HIV-positive and had a higher prevalence of low-risk HPV types (odds ratio [OR] 5.28, P=0.005) compared with HIV-negative women. The most common high-risk (HR)-HPV types in HIV-positive women were HPV 16 (13.9%) and HPV 18 (11.1%). HIV-positive women requiring LEEP were more likely to have HR-HPV types (OR 6.67, P=0.012) and to be infected with multiple HR-HPV types (OR 7.79, P=0.024) compared to those undergoing cryotherapy. Conclusion HIV-positive women requiring LEEP versus cryotherapy had a higher prevalence of any HR-HPV type and multiple HR-HPV types. There were no such differences in HPV types identified among HIV-negative women.

Background Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor. Methods Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration. Results Valid HPV testing results were available for 86 women (mean age 34.0 years); 49 women (57.0%) had AFB1-lys detected and 37 (43.0%) had none. The AFB1-lys detection was not associated with age, being married, having more than secondary school education, home ownership, living at a walking distance to healthcare ≥60 minutes, number of lifetime sex partners, or age of first sex. The AFB1-lys detection and plasma concentrations were associated with detection of oncogenic HPV types. Conclusions The AFB1-lys positivity and higher plasma AFB1-lys concentrations were associated with higher risk of oncogenic HPV detection in cervical samples from Kenya women. Further studies are needed to determine whether aflatoxin interacts with HPV in a synergistic manner to increase the risk of cervical cancer.

Background AIDS-related Kaposi sarcoma (AIDS-KS), a common malignancy in Kenya is associated with high morbidity and mortality. AIDS-KS is treated using bleomycin and vincristine (BV) plus or minus doxorubicin in most low resource settings, with response rates ranging from 24.8 to 87%. Survival in low resource settings has not been well documented. We report the three-year survival in a cohort of seventy patients referred to Moi Teaching and Referral Hospital (MTRH). Methods Study participants are part of a randomized phase IIA trial on the use of gemcitabine compared to bleomycin plus vincristine for the treatment of Kaposi sarcoma after combination antiretroviral therapy (cART) in Western Kenya. All patients were followed for three years in MTRH. Survival was determined by three monthly physical examination and analysed using Kaplan-Meier method, while possible determinants of survival such as baseline characteristics, type of chemotherapy, initial CD4 counts, age at enrolment, gender and early response to chemotherapy were analysed using univariate and multivariate Cox regression. Results Participants were aged between 19 and 70 years with 56% being male. The median CD4 count was 224 cells/μl, median duration of HIV diagnosis was 12.0 months and median duration of KS lesions after histology diagnosis before initiating chemotherapy was 4.8 weeks. At three years, 60 (85.7%) patients were alive. Six of those who died were under treatment with BV while four with gemcitabine. There was no difference in the probability of survival between the patients on either treatment arm (HR = 0.573 [95% C. I 0.143, 2.292; p = 0.4311]). Additionally, the hazard ratio (HR) for response after six weeks, age at enrolment and gender indicated that they were not significant determinants of survival. Patients with normal CD4 cell counts (> = 500/μl), had a HR of 0.401(0.05,3.23; p = 0.391), suggesting better survival. Conclusions Patients with AIDS-KS treated with combined antiretroviral drugs had excellent three-year survival regardless of whether they were treated with BV or gemcitabine as first line therapy. An initial CD4 cell count of > = 500/μl appeared to improve survival while gender, age and early response to chemotherapy were not predictors of survival after three years. Trial registration Number PACTR201510001.

11000 Background: Childhood cancer has an annual incidence of 150-160 cases per million children worldwide but remains vastly under-diagnosed in low to middle income countries (LMIC) such as in Sub-Saharan Africa. Moi Teaching and Referral Hospital (MTRH) is the only tertiary referral hospital in western Kenya and serves a population of 25 million people, including 10 million children. The average number of pediatric cancer diagnoses was 216 cases annually in 2017-2019, well below the anticipated 1500 cases based on cancer epidemiology data. We recently completed a comprehensive Needs Assessment suggesting that due to inadequate pediatric oncology education, many clinical diagnoses are missed and correct diagnostic tests are not obtained at county hospitals. Local medical staff expressed interest in educational programs to help augment their understanding and diagnostic evaluation of pediatric oncology. Methods: To address these disparities in medical knowledge, we implemented Project ECHO – a validated virtual guided practice and telementoring model – to connect multidisciplinary specialists at MTRH with staff in medically underserved communities in western Kenya for ongoing training, technical assistance, and mentorship. The ECHO program follows a Hub-and-Spoke design where the specialists at MTRH and pediatric oncologists at Riley Hospital functioned as the “hub” team and the health care workers at county hospitals were the “spokes”. Sessions were freely available on Zoom twice monthly and featured both a didactic topic presented by experts and a spoke-led case-based discussion. The discussion utilized dialogue education to promote learning and engagement among the spokes with mentorship from the hub team. Results: The ECHO program launched successfully in January 2020 with a curriculum focused on pediatric oncology for general health care workers. A total of 22 sessions occurred with an average of 23 learners (primarily staff at community hospitals within the referral region) per session. Despite the COVID-19 pandemic, the year-end analysis in January 2021 demonstrated 286 new pediatric patients were diagnosed with cancer at MTRH representing a 33% increase over the 3-year average. Conclusions: The implementation of a telehealth education platform – Project ECHO – focused on diagnosing pediatric cancer in medically underserved communities in Kenya, is a useful model to increase the recognition and earlier referral of childhood cancer in LMICs.

8579 Background: Thymic epithelial tumors (TET) are one of the rarest adult malignancies. Overall, patients have favorable survival outcomes, however a small subset develop metastatic disease. Genomic characterization of this very rare, clinically aggressive TET subset is lacking. Herein, we evaluated the clinical and genomic characteristics of metastatic TET (mTET) compared to a large cohort (n = 117) of primary TET (pTET) from The Cancer Genome Atlas (TCGA). Methods: From 2015 to 2020, 52 pts with mTET underwent clinical CLIA-based sequencing using either whole-exome (n = 35), panel-based testing (n = 13) and/or liquid biopsy (n = 22). The specimen was taken from a metastatic organ (n = 34) or relapsed primary mediastinal mass (n = 14); 4 pts had liquid bx only. Data on pTET was derived from the TCGA. Kaplan-Meier and log-rank test was used for assessment of PFS, OS. Results: The median age was 56 yrs in mTET (range 32-74) vs. 60 yrs (range 17-84) in TCGA data. The M/F (%) was 40/60 in mTET and 48/52 in TCGA, respectively. Of note, 13 mTET pts had other types of cancer prior or concurrent with TET diagnosis (4-breast, 2-bladder, 5-other) in which radiotherapy (n = 4) and/or chemotherapy (n = 3) was administered prior to TET diagnosis. In our cohort, 19 pts had stage IVA and 33 pts had stage IVB (most common metastatic site was liver in 17 pts). WHO histologic classification was: A = 1, A/B = 3, B1 = 4, B2 = 10, B3 = 12, TC = 18, TC with neuroendocrine feature = 3, and lymphoepithelial carcinoma = 1. WHO B3 and TC histologies were more common in our cohort of mTET than in the TCGA cohort (63% (33/52) vs. 17% (20/117), respectively). Pts with TC had worse mOS compare to thymoma (109m vs. 163m, HR = 2.78, P = 0.04). The most common genomic alteration in mTET was TP53 (n = 17, 33%) compared to 3% in TCGA. This was followed by CDKN2A (n = 5, 10%), PIK3CA (n = 4, 8%), CDKN2B (n = 3, 6%) and NF1 (n = 3, 6%). All TP53 missense mut functionality was analyzed with polyphen-2 software and 91.6% (22/24) had 98-100% damaging probability. 70% of pts that harbored TP53 muts were TC (41%) or B3 (29%) histology. Clinically actionable genomic alterations targetable with available or investigational agents (e.g. high TMB; gain-of-function mutations in PIK3CA, CDK4, and mTOR; loss-of-function mutations in NF1) were seen in 23% (12/52) of pts. Conclusions: Patients with mTET are associated with more aggressive WHO histology (B3 and TC). Greater frequency of TP53 mutations are observed in mTET compared to pTET. Clinically actionable genomic alterations are frequently seen in mTET suggesting value in the routine sequencing of these patients.

10556 Background: Cancer is the third leading cause of death with about 48,000 new yearly diagnoses in Kenya. Breast and cervical cancers are the major leading cancers in females, both of which are curable with access to timely and effective care. To meet population health goals, early abnormalities of the cervix and breast must be treated promptly to maximize the chance for cure. The AMPATH Breast and Cervical Cancer Control Program (ABCCCP) was initiated to improve access to screening and diagnostic services for breast and cervical cancer in Kenya by addressing the barriers of cancer care through a population health approach, working with communities and the Ministry of Health in Kenya with a potential for scaling these efforts to other parts of the region. Methods: We performed an interim analysis 3 years into a 5-year program, to assess the impact of COVID-19 on our screening program. Statistical descriptive summaries were used to show the trend of screening using visual inspection with acetic acid and breast clinical examination. The screening was conducted facility-based along with community screening upon requests across nine counties. Also, we conducted capacity building through mentoring of health care providers and initiating a telemedicine program to improve patient care and management plans. Results: From 2018-2021, we conducted training, connected 12 centers with telemedicine capacity and screened a total of 100,973 persons were for breast and cervical cancer. The yearly trends demonstrate that the facility routine screenings were maintained: 23,421 (2018); 27,997 (2019); and 28,045 (2020). The total women seen through organized mass screenings however declined (10,304 (2018); 10,107 (2019); and 1,099 (2020), respectively) as this type of screening was stopped after the onset of COVID-19 pandemic. Of all women screened, 3,019 (2.98%) had clinical abnormalities requiring follow-up per standard of care including 1,781(1.8%) who were eventually histologically confirmed to have cancer. During our first and second year of the program, 83 physicians were trained on cancer management and treatment, 341 nurses were trained on breast and cervical cancer screening procedures, and 247 community health workers (CHW) were trained on the importance of screening to enlighten the community on awareness. However, this training was suspended in our year three due to COVID-19. Conclusions: An integrated training program utilizing CHW, nurses and physicians are an effective means for breast and cervical cancer screening in LMC, such as Kenya. This capacity building allows flexibility and sustainability even in the midst of the global COVID-19 pandemic. We also demonstrated successful integration with the county government for program sustainability. The use of telemedicine has greatly enhanced our screening and patient care across several facilities in western Kenya.

Simple Summary Thymic carcinoma (TC) is a rare neoplasm that accounts for less than 0.01% of all tumors. The aim of our retrospective observational analysis is to review the incidence of second cancers associated with this histological type of cancer. We identified 92 patients with TC referred to our consultation practice and reviewed their clinical data for diagnosis of another cancer pre- or post-diagnosis of TC. This resulted in identification of 14 patients with additional cancers. The incidence of second cancer is similar to that observed in thymomas. Abstract Thymic carcinomas account for less than 0.01% of new cancer diagnoses annually and are more aggressive than thymomas. Autoimmune disorders have been associated with thymomas and only recently with thymic carcinomas. Second malignancies are well described after thymomas. The aim of this study was to analyze the incidence of second malignancies in patients with thymic carcinomas. All cases of thymic carcinomas were identified from the pathology archives of Indiana University. Histological materials were reviewed and further correlated with clinical data to identify incidence of second cancers in patients with thymic carcinomas. Histological material was available for review in 92 cases of thymic carcinoma. Clinical data were available for 85 patients. Fourteen of these (16.5%) patients had a second malignancy; these included small cell lung carcinoma, “testicular cancer”, embryonal carcinoma, seminoma, breast carcinoma (two cases), prostatic adenocarcinoma, Hodgkin’s lymphoma, thyroid carcinoma, bladder carcinoma (two cases), renal cell carcinoma, and melanoma. The latter could precede, be concurrent with, or follow the diagnosis thymic carcinoma. The incidence of second cancers in patients with thymic carcinomas is similar to that reported for thymomas. Abnormalities in immunological surveillance may be responsible for this high incidence of second malignancies in thymic tumors.

Adjuvant therapy after surgical resection is the current standard for pancreatic adenocarcinoma; however, the role of chemoradiotherapy (CRT) remains unclear. This study was conducted to compare the efficacy outcomes with adjuvant gemcitabine and gemcitabine-based CRT (CT-CRT) versus gemcitabine chemotherapy (CT) alone after pancreaticoduodenectomy.Among 165 patients who underwent surgical resection for pancreatic cancer at Indiana University Medical Center between 2004 and 2008, we retrospectively identified 53 consecutive patients who received adjuvant therapy (CT-CRT=34 patients; CT=19 patients) and had adequate follow-up medical records. The median follow-up was 19.1 months. Median disease-free (DFS) and overall survival (OS) were determined using Kaplan-Meier method, and a Cox-regression model was used to compare survival outcomes after adjusting for age, status of resection margins, and lymph node involvement.The OS for the CT-CRT group was significantly higher compared with the CT group (median, 20.4 vs. 16.6 mo; hazard ratio, 2.42; 95% CI, 1.17-5.01). The median DFS for the CT-CRT group was 13.7 versus 11.1 months for the CT group (hazard ratio, 2.88; 95% CI, 1.37-6.06). On subgroup analyses, significantly superior OS and DFS were observed among patients younger than 65 years, T3/T4 tumor stage, negative resection margins, and positive lymph node involvement.Gemcitabine plus gemcitabine-based CRT compared with gemcitabine alone leads to superior DFS and OS for patients with resected pancreatic cancer.

// Milan Radovich 1,2,* , Patrick J. Kiel 1,2,* , Stacy M. Nance 1 , Erin E. Niland 1 , Megan E. Parsley 1 , Meagan E. Ferguson 1 , Guanglong Jiang 2 , Natraj R. Ammakkanavar 2 , Lawrence H. Einhorn 2 , Liang Cheng 2 , Mehdi Nassiri 2 , Darrell D. Davidson 2 , Daniel A. Rushing 2 , Patrick J. Loehrer 2 , Roberto Pili 2 , Nasser Hanna 2 , J. Thomas Callaghan 2 , Todd C. Skaar 2 , Paul R. Helft 2 , Safi Shahda 2 , Bert H. O’Neil 2 and Bryan P. Schneider 1,2 1 Indiana University Health Precision Genomics Program, Indianapolis, IN, USA 2 Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA * These authors have contributed equally to this work Correspondence to: Bryan P. Schneider, email: // Keywords : precision medicine, personalized medicine, genomics, next-generation sequencing Received : June 07, 2016 Accepted : June 09, 2016 Published : July 15, 2016 Abstract Patients and Methods: Patients with metastatic solid tumors who had progressed on at least one line of standard of care therapy were referred to the Indiana University Health Precision Genomics Program. Tumor samples were submitted for DNA & RNA next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry for actionable targets. A multi-disciplinary tumor board reviewed all results. For each patient, the ratio of progression-free survival (PFS) of the genomically guided line of therapy divided by the PFS of their prior line was calculated. Patients whose PFS ratio was ≥ 1.3 were deemed to have a meaningful improvement in PFS. Results: From April 2014–October 2015, 168 patients were evaluated and 101 patients achieved adequate clinical follow-up for analysis. 19 of 44 (43.2%) patients treated with genomically guided therapy attained a PFS ratio ≥ 1.3 vs . 3 of 57 (5.3%) treated with non-genomically guided therapy ( p < 0.0001). Similarly, overall PFS ratios (irrespective of cutoff) were higher for patients with genomically guided therapy vs non-genomically guided therapy ( p = 0.05). Further, patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs . 49 days, p = 0.005, H.R. = 0.55, 95% C.I.:0.37-0.84). Conclusion: Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.

Purpose More than 80% of women with breast cancer in Kenya present to medical care with established late-stage disease. We sought to understand why women might not participate in breast cancer screening when it is offered by comparing the views of a cohort of those who attended a screening special event with those of community controls who did not attend. Methods All residents living close to three health centers in western Kenya were invited to participate in screening. Participants (attendees) underwent clinical breast examination by trained physician oncologists. In addition, women who consented were interviewed by using a modified Breast Cancer Awareness Module questionnaire. Nonattendees were interviewed in their homes the following day. Results A total of 1,511 attendees (1,238 women and 273 men) and 467 nonattendee women participated in the study. Compared with nonattendees, the women attendees were older, more often employed, knew that breast cancer presented as a lump, and were more likely to have previously felt a lump in a breast. In addition, they were more likely to report previously participating in screening activities, were more likely to have performed breast self-examination, and were less concerned about wasting a doctor’s time. Almost all those surveyed (attendees and nonattendees) expressed interest in future breast cancer screening opportunities. Conclusion The women who volunteer for breast cancer screening in western Kenya are more aware of breast cancer than those who do not volunteer. Screening recruitment should seek to close these knowledge gaps to increase participation.

7 Background: Panitumumab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) and is a standard therapy in KRAS/NRAS/BRAF WT mCRC. Preclinical data shows that anti-EGFR therapy causes a tumor-specific adaptive immune response and immunogenic apoptosis, with functional adaptive immunity required to mediate efficacy. However, resistance to anti-EGFR antibody therapy inevitably develops and is associated with increased expression of CTLA-4 and PD-L1. We hypothesized that addition of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) to panitumumab will increase response rate in patients with KRAS/NRAS/BRAF WT MSS mCRC. Methods: LCCC1632 was a multicenter, single-arm, Simon’s two stage phase II clinical trial with a pre-specified safety run-in of panitumumab, ipilimumab, and nivolumab in KRAS/NRAS/BRAF WT, MSS mCRC (NCT03442569). Eligible patients must have received 1-2 prior lines of therapy and no prior anti-EGFR or immune checkpoint inhibitor therapy. Subjects received ipilimumab 1 mg/kg IV q6wk, nivolumab 240 mg IV q2wk, and panitumumab 6 mg/kg IV q2wk until progression, toxicity, or patient withdrawal. The primary endpoint was response rate at 12 weeks per RECIST 1.1, and key secondary endpoints included progression-free survival and duration of response. Results: A total of 56 subjects were enrolled 3/2018-6/2020. This included the 6-subject safety run-in, with 0/6 dose-limiting toxicities in first 12 weeks. The first stage of the Simon’s two-stage clinical trial (n=32) had sufficient response rate to merit full enrollment. There were 7 unevaluable subjects for the primary endpoint of 12-week response rate. Among 49 evaluable subjects, 12-week response rate was 35% (95% CI 21-48; n=17 responses). Twenty subjects had at least an unconfirmed response at any time. Median PFS was 5.7 months (95% CI 5.5-7.9). There was one treatment-related grade 5 adverse event of myocarditis. The most common treatment-related grade 3-4 AEs included lipase increased (9%), amylase increased (7%), ALT increased (5%), AST increased (5%), diarrhea (5%), hypophosphatemia (5%), and maculopapular rash (5%). Conclusions: The combination of panitumumab, ipilimumab, and nivolumab demonstrated evidence of activity and met its prespecified primary endpoint of 12-wk response rate criteria to merit further study. The PFS in this single-arm study compares favorably to expected PFS for anti-EGFR monotherapy in RAS wild-type patients, and results suggest activity of immune checkpoint inhibitors combined with anti-EGFR therapy in MSS mCRC. Clinical trial information: NCT03442569.

e16764 Background: Both EGFR and the c-MET receptors are overexpressed in a majority of PDACs. Inhibition of both receptors simultaneously may be required for anti-tumor activity. Erlotinib, an EGFR inhibitor, has modest activity in metastatic PDAC and is approved by the FDA in combination with gemcitabine. Cabozantinib is a tyrosine kinase inhibitor targeting AXL, FLT-3, KIT, MER, MET, RET, ROS1, TIE-2, TRKB, TYRO3, and VEGFR-1, -2, and -3. Preclinical data suggests that the addition of cabozantinib to erlotinib leads to tumor shrinkage and improvement in survival in a KPC PDAC mouse model compared to gemcitabine alone. This phase II study tests this hypothesis in patients with metastatic PDAC that co-express c-MET and EGFR. Methods: Key eligibility includes patients (pts) with metastatic PDAC with EGFR and c-MET overexpression (as determined by centrally tested IHC of 2+ or greater) that have progression on one prior chemotherapy regimen. Patients were treated with cabozantinib (40mg daily) and erlotinib (100mg daily) continuously. This dosing is based on previous combination data in NSCLC. This is a single arm two-stage phase II study with a primary endpoint of overall response rate. Secondary endpoints include of PFS, DCR and OS. Results: From October 2017 to October 2019, 43 pts were screened with 7 pts (median age 62 [range 51-76)] enrolled and treated on study. Pts had a median of 1 line of prior systemic chemotherapy. Most common reason for screen failure was due to lack of co-expression of c-MET and EGFR. EGFR IHC expression was +2 in 4 pts, +3 in 3 pts; c-MET IHC expression was +2 in 5 pts and +3 in 2 pts. Most common any-grade adverse events attributable to cabozantinib and erlotinib include: diarrhea (71%), AST increase (43%), fatigue (43%), nausea (43%), and rash (43%). Only one grade 3 event of fatigue occurred. All pts had clinical and/or radiographic progression within 1-2 months after initiating study therapy. Conclusions: The combination of cabozantinib and erlotinib was well tolerated with manageable toxicity. Due to lack of clinical responses, this study has been terminated due to futility. Clinical trial information: NCT03213626 .