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Background Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin’s lymphoma worldwide and particularly in Africa, where the incidence of HIV is the highest in the world. R-CHOP is the standard of care regimen for DLBCL, but access to rituximab is limited in developing countries. Methods This is a retrospective cohort study that included all HIV-negative patients with DLBCL who received R-CHOP at a single institution from January 2012 to December 2017. Clinical and demographic data were collected to assess factors that influenced survival. Results Seventy-three patients were included. Median age was 55 (17-76), 67.1% of patients were younger than 60 years, and 60.3% were female. Most presented with stages III/IV disease (53.5%) but with good performance status (56.% PS 0 and 1). Progression-free survival at 3 and 5 years was 75% and 69%, and overall survival at 3 and 5 years was 77% and 74%, respectively. Median survival had not been reached with a median follow-up of 3.5 years(0.13-7.9). Overall survival was significantly affected by performance status (P = .04), but not by IPI or age. Survival was significantly associated with response to chemotherapy after 4-5 cycles of R-CHOP (P = 0.005). Conclusions Treatment of DLBCL with R-CHOP is feasible and can achieve good outcomes in resource-limited settings with rituximab-based chemotherapy. Poor performance status was the most important adverse prognostic factor in this cohort of HIV-negative patients.

Background: Endocrine therapy with CDK 4/6 inhibitors (ET/CDK4/6i) represents the 1st line therapy for ER+/HER2- ABC. While majority of patients derive clinical benefit with combination therapy, a subset have refractory disease with progression within 6 months. However, predictive biomarkers for rapid progression are lacking. In this study, we evaluated genomic profiles associated with rapid disease progression on ET/CDK4/6i. Methods: We identified 77 patients who received 1st line ET/CDK4/6i combination therapy (AI or SERD with one of the 3 approved CDK4/6is) and had ctDNA analysis performed via plasma based genotyping utilizing the commercially available Guardant360 assay at three sites: Washington University in St. Louis, MO, Northwestern University (Chicago, IL), and Massachusetts General Hospital (Boston, MA). We aimed to look at the differences in patient characteristics and genomic profiles of the tumors assessed from baseline ctDNA specimens between the patients with rapid progression (time to progression TTP Citation Format: Marko Velimirovic, Lorenzo Gerratana, Andrew A Davis, Whitney L Hensing, Katherine Clifton, Ami N Shah, Paolo D'Amico, Charles S Dai, Elyssa N Denault, Cynthia X Ma, Seth A Wander, Dejan Juric, Massimo Cristofanilli, Bruce A Chabner, Aditya Bardia. Genomic predictors of rapid progression to first line endocrine and CDK4/6 inhibitor combination therapy in patients with estrogen receptor positive (ER+) HER-2 negative (HER2-) advanced breast cancer (ABC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-07-02.

We evaluated the efficacy and safety of poly-(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 inhibitor veliparib and temozolomide in metastatic breast cancer patients with and without germline BRCA1/2 mutations. In this single-arm phase II trial, patients with metastatic breast cancer received veliparib 30 to 40 mg twice daily on days 1 to 7 with concurrent temozolomide 150 mg/m2 on days 1 to 5 of a 28-day cycle. The primary cohort was unselected for BRCA mutation status, and an expansion cohort enrolled only BRCA1/2 carriers. The primary endpoint was objective response rate (ORR) in each cohort. Secondary endpoints included progression-free survival (PFS), clinical benefit rate (CBR), and evaluation of safety and tolerability. In the primary cohort of 41 unselected patients, which included 9 BRCA mutation carriers, the ORR was 10% and clinical benefit rate at 4 months (CBR) was 27%. In the expansion cohort of 21 BRCA1/2 carriers, the ORR was 14% and CBR was 43%. Among all 30 BRCA1/2 carriers, the ORR was 23% versus 0% among non-carriers. In the subset of BRCA1/2 carriers, the ORR was 32% among platinum-naive patients versus 9% among platinum-exposed patients. The median PFS was 3.3 months among BRCA1/2 carriers compared to 1.8 months among non-carriers (HR: 0.48, p = 0.006). A longer median PFS of 6.2 months was observed among BRCA1/2 carriers who had no prior platinum therapy. The most common grade 3 and 4 toxicities were thrombocytopenia (32%) and neutropenia (21%) that generally improved with dose modifications. Veliparib and temozolomide demonstrated clinical activity in platinum-naive BRCA-associated metastatic breast cancer with manageable toxicity at doses of veliparib well below the single-agent active dose. Although the study did not meet its primary endpoint in unselected nor BRCA-associated breast cancer, this regimen was further evaluated in the BROCADE 2 study. NCT01009788 (ClinicalTrials.gov), November 9, 2009

In the context of cancer, whether or not to choose pregnancy termination represents a difficult and multifaceted decision. In this editorial, members of The Oncologist editorial team attempt to contextualize the potential implications of the recent Supreme Court decision in Dobbs v. Jackson Women’s Health Organizationfor patients with cancer.

PURPOSE Accurate monitoring of therapeutic response remains an important unmet need for patients with metastatic breast cancer (MBC). Analysis of tumor genomics obtained via circulating tumor DNA (ctDNA) can provide a comprehensive overview of tumor evolution. Here, we evaluated ctDNA change as an early prognostic biomarker of subsequent radiologic progression and survival in MBC. PATIENTS AND METHODS Paired blood samples from patients with MBC were analyzed for levels of ctDNA, carcinoembryonic antigen, and cancer antigen 15-3 at baseline and during treatment. A Clinical Laboratory Improvement Amendments–certified sequencing panel of 73 genes was used to quantify tumor-specific point mutations in ctDNA. Multivariable logistic regression analysis was conducted to evaluate the association between ctDNA rise from baseline to during-treatment (genomic progression) and subsequent radiologic progression and progression-free survival (PFS). RESULTS Somatic mutations were detected in 76 baseline samples (90.5%) and 71 during-treatment samples (84.5%). Patients with genomic progression were more than twice as likely to have subsequent radiologic progression (odds ratio, 2.04; 95% CI, 1.74 to 2.41; P < .0001), with a mean lead time of 5.8 weeks. Genomic assessment provided a high positive predictive value of 81.8% and a negative predictive value of 89.7%. The subset of patients with genomic progression also had shorter PFS (median, 4.2 v 8.3 months; hazard ratio, 2.97; 95% CI, 1.75 to 5.04; log-rank P < .0001) compared with those without genomic progression. CONCLUSION Genomic progression, as assessed by early rise in ctDNA, is an independent biomarker of disease progression before overt radiologic or clinical progression becomes evident in patients with MBC.

PURPOSE With intense HIV epidemics, southern African countries have a high burden of classic Hodgkin lymphoma (CHL) and non-Hodgkin lymphoma (NHL). However, suboptimal access to pathology resources limits subtype classification. We sought to assess the diagnostic accuracy of specimens classified as lymphoma and to determine association between discordant pathologic diagnosis and overall survival. METHODS Seventy patients with CHL or NHL and treated at three Botswana hospitals from 2010 to 2016 were analyzed. Local pathologic assessment relied primarily on morphology. All cases underwent secondary US hematopathology review, which is considered gold standard. RESULTS The median follow-up was 58 months. The overall reclassification rate was 20 of 70 cases (29%). All 20 CHL cases were correctly classified in Botswana, and mixed cellularity was the most common subtype, diagnosed in 11 (55%) cases. Of 47 confirmed NHL cases, diffuse large B-cell lymphoma was the final US diagnosis in 28 cases (60%), another aggressive B-cell NHL in nine (19%), an indolent B-cell NHL in six (13%), and T-cell NHL in four (9%). Common types of diagnostic discordance included NHL subtype reclassification (11 of 20, 55%) and CHL reclassified as NHL (7 of 20, 35%). Concordant versus discordant diagnosis after secondary review was associated with improved 5-year overall survival (60.1% v 26.3%, P = .0066). Discordant diagnosis was independently associated with increased risk of death (adjusted hazard ratio 2.733; 95% CI, 1.102 to 6.775; P = .0300) even after stratifying results by CHL versus NHL. CONCLUSION In this single prospective cohort, discordant pathologic diagnosis was associated with a nearly three-fold increased risk of death. Limited access to relatively basic diagnostic techniques impairs treatment decisions and leads to poor patient outcomes in low-resource countries.

The editors of The Oncologist offer suggestions for summer reading of books that provide insight into our field of endeavor, our civil discourse, and our personal lives.

What are the prospects for dealing with COVID-19 more effectively in the future? This editorial addresses the question from the perspective of long-term control of coronavirus infection.

Financial barriers may discourage some patients with from participating in cancer clinical trials. This study sought to assess the effect of an equity intervention on the financial burden of clinical trial participants., Background. The financial burden experienced by patients with cancer represents a barrier to clinical trial participation, and interventions targeting patients’ financial concerns are needed. We sought to assess the impact of an equity intervention on clinical trial patients’ financial burden. Materials and Methods. We developed an equity intervention to reimburse nonclinical expenses related to trials (e.g., travel and lodging). From July 2015 to July 2017, we surveyed intervention and comparison patients matched by age, sex, cancer type, specific trial, and trial phase. We longitudinally assessed financial burden (e.g., trial‐related travel and lodging cost concerns, financial wellbeing [FWB] with the COmprehensive Score for financial Toxicity [COST] measure) at baseline, day 45, and day 90. We used longitudinal models to assess intervention effects over time. Results. Among 260 participants, intervention patients were more likely than comparison patients to have incomes under $60,000 (52% vs. 24%, p < .001) and to report travel‐related (41.0% vs. 6.8%, p < 0.001) and lodging‐related (32.5% vs. 2.0%, p < .001) cost concerns at baseline. Intervention patients were more likely to report travel to appointments as their most significant financial concern (24.0% vs. 7.0%, p = .001), and they had worse FWB than comparison patients (COST score: 15.32 vs. 23.88, p < .001). Over time, intervention patients experienced greater improvements in their travel‐related (−10.0% vs. +1.2%, p = .010) and lodging‐related (−3.9% vs. +4.0%, p = .003) cost concerns. Improvements in patients reporting travel to appointments as their most significant financial concern and COST scores were not statistically significant. Conclusion. Cancer clinical trial participants may experience substantial financial issues, and this equity intervention demonstrates encouraging results for addressing these patients’ longitudinal financial burden. Implications for Practice. Clinical trials are critical for developing novel therapies for patients with cancer, yet financial barriers may discourage some patients from participating in cancer clinical trials. This study found that patients who received financial assistance from an equity intervention experienced significant improvements over time in their concerns about the cost of travel and lodging associated with clinical trials compared with comparison patients who did not receive financial assistance from the equity intervention. Among cancer clinical trial participants, an equity intervention shows potential for addressing patients' concerns regarding clinical trial‐related travel and lodging expenses.

The past and future Editors-in-Chief of The Oncologist offer thoughts on the recent U.S. Supreme Court leak and its significance for other areas of medical practice.

Dr. Chabner, Editor-in-Chief of The Oncologist, announces his retirement, with a look back at the origins of the journal and a look forward to the future.

This editorial focuses on the current state of science and public health in the U.S. during the 2020 presidential election season.

Lessons Learned The findings from this study using monotherapy with pemetrexed in a pretreated patient population are, overall, encouraging. Unlike high-dose methotrexate, which requires several days of inpatient hospitalization, pemetrexed is relatively easy to administer in the outpatient setting and remains a viable treatment option in this patient population. The maximum tolerated dose of pemetrexed administered (900 mg/m2 every 2 weeks) was generally well tolerated and showed activity in patients with relapsed or refractory CNSL. Background There is currently no standard salvage treatment for patients with relapsed/refractory central nervous system (CNS) lymphoma (CNSL). We report the results of a phase I study of pemetrexed, an antifolate drug with broader activity than methotrexate (MTX). We provide the safety, tolerability, and maximum tolerated dose (MTD) of pemetrexed in patients with recurrent CNSL. Methods Through October 2015, 17 patients with relapsed/refractory CNSL received pemetrexed every 2 weeks with the first cohort receiving 600 mg/m2 and dose escalation in increments of 300 mg/m2 to a maximum of 1,200 mg/m2. Three patients were to enroll at each dose level with expansion to six patients in the event of dose-limiting toxicity. Patients with both primary CNS lymphoma (PCNSL) and secondary CNS lymphoma (SCNSL) could be enrolled. Results Seventeen patients were evaluable with a median age of 63.7 years. Main adverse events included fatigue (82.4%), anemia (82.4%), and neutropenia (70.6%). The MTD was established at 900 mg/m2. Dose-limiting toxicities were recorded in one patient in the 600 mg/m2 cohort and in two patients in the 1,200 mg/m2 cohort. Fourteen patients were evaluable for response assessment; 21.4% achieved a complete response, 35.7% had a partial response, 14.3% had stable disease, and 28.6% had progressive disease. The median progression-free survival was 4.2 months. The median overall survival was 44.5 months. In the original study protocol, the plan was to add an expansion cohort of six patients at MTD level. However, the first phase of the study was characterized by slow recruitment. Therefore, after achieving the primary objective of the study and establishing the MTD, the investigators decided to amend the protocol and to close the study. Conclusion Pemetrexed administered at 900 mg/m2 every 2 weeks exhibits single-agent activity in patients with recurrent CNSL; it is well tolerated, and side effects are manageable.

The FDA has ordered the withdrawal of all ranitidine products from the marketplace based on recent findings of increased and unacceptable levels of N-nitrosodimethylamine (NDMA). This commentary reviews the sources and properties of NDMA, assesses the dangers it poses, and suggests measures to mitigate contamination.

(Abstracted from N Engl J Med 2018;379(18):1754–1765)Tumor biopsies represent the standard for cancer diagnosis and the primary method for molecular testing to guide the selection of precision therapies. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly eme

The identification of patients with aggressive cancer who require immediate therapy is a health challenge in low- and middle-income countries. Limited pathology resources, high healthcare costs and large caseloads call for the development of advanced stand-alone diagnostics. Here, we report and validate an automated, low-cost point-of-care device for the molecular diagnosis of aggressive lymphomas. The device uses contrast-enhanced microholography and a deep learning algorithm to directly analyse percutaneously obtained fine-needle aspirates. We show the feasibility and high accuracy of the device in cells, as well as the prospective validation of the results in 40 patients clinically referred for image-guided aspiration of nodal mass lesions suspicious of lymphoma. Automated analysis of human samples with the portable device should allow for the accurate classification of patients with benign and malignant adenopathy. A low-cost point-of-care device that uses contrast-enhanced microholography and deep learning accurately detects aggressive lymphomas in patients referred for aspiration and biopsy of enlarged lymph nodes.

Purpose Botswana has a high prevalence of HIV infection. Currently, there are few data regarding the sociodemographic factors, clinical characteristics, and outcomes of non-Hodgkin lymphoma (NHL)—an AIDS-defining cancer—in the country. Patients and Methods This study used a prospective cancer registry to identify patients with a new diagnosis of NHL reporting for specialty cancer care at three hospitals in Botswana between October 2010 and August 2016. Treatment patterns and clinical outcomes were analyzed. Results One hundred four patients with a new diagnosis of NHL were enrolled in this study, 72% of whom had HIV infection. Compared with patients not infected with HIV, patients infected with HIV were younger (median age, 53.9 v 39.1 years; P = .001) and more likely to present with an aggressive subtype of NHL (65.5% v 84.0%; P = .008). All patients infected with HIV received combined antiretroviral therapy throughout the course of the study, and similar chemotherapeutic regimens were recommended for all patients, regardless of subtype or HIV status (six to eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone; or cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab). There was no difference in 1-year mortality among patients not infected with HIV and patients infected with HIV (unadjusted analysis, 52.9% v 37.1%; hazard ratio [HR], 0.73; P = .33; adjusted analysis, HR, 0.57; P = .14). However, when compared with a cohort of patients in the United States matched by subtype, stage, age, sex, and race, patients in Botswana fared worse (1-year mortality, 22.8% v 46.3%; HR, 1.89; P = .001). Conclusion Among patients with NHL reporting for specialty cancer care in Botswana, there is no association between HIV status and 1-year survival.

86 Background: Cancer clinical trial (CCT) participants are at risk for experiencing adverse effects from financial toxicity, yet these remain understudied. We sought to describe associations among CCT participant-reported financial toxicity (financial burden [FB] and trial cost concerns), symptoms, illness perceptions, communication confidence, hospitalizations, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance (n = 100) and a patient group matched by age, sex, cancer type, specific trial, and trial phase (n = 98). We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, as well as their associations with symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. We also used Kaplan-Meier and regression methods to evaluate their associations with 6-month hospitalizations and survival. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) with lower incomes (< $100,000, OR 4.61, 95% CI 2.35-9.01). Patients with trial cost concerns had lower incomes (< $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS (OR 1.03, 95% CI 1.02-1.05), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS (OR 1.03, 95% CI 1.01-1.05), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Financial toxicity was not significantly associated with hospitalizations or survival. Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptoms, more negative illness perceptions, and lower communication confidence, underscoring the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.

160 Background: Patients’ perceptions of their illness are important for treatment decision-making and quality of life. Limited data exist describing associations of illness perceptions with other patient-centered outcomes, particularly in CCT participants. We sought to examine associations among illness perceptions and CCT patients’ financial toxicity, physical and psychological symptoms, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance programs (n = 157) and a group of patients matched by age, sex, cancer type, specific trial, and trial phase (n = 103). We assessed baseline illness perceptions (Brief Illness Perceptions Questionnaire [BIPQ] with scores > 50 indicating negative perceptions), financial toxicity (degree costs of cancer care have been a burden, moderate to catastrophic indicating financial toxicity), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used descriptive statistics to examine associations of BIPQ and sociodemographic/clinical factors, financial toxicity, ESAS, PHQ-4, and overall survival. We used the Kaplan-Meier method to estimate median survival times and Cox regression to assess the association of BIPQ and overall survival. Results: Among 260 patients, 189 (72.7%) completed BIPQ surveys (median age 69 [Range 26 to 83] years, 66.1% female). 68.8% had negative illness perceptions. We found no significant associations among negative illness perceptions and patients’ age, sex, race, education, marital status, performance status, insurance, cancer type, metastatic disease status, self-reported income, trial phase, trial year, or Charlson Comorbidity Index score. Patients with negative illness perceptions were more likely to report financial toxicity (69.8% vs 48.8%, p = 0.006), and had higher ESAS-total (Medians: 44 [Range 0-89] vs 21 [Range 0-78], p < 0.001), PHQ-4 depression (Medians: 2 [Range 0-6] vs 0 [Range 0-6], p < 0.001), and PHQ-4 anxiety (Medians: 3 [Range 0-6] vs 1 [Range 0-6], p < 0.001) scores. Patients with negative illness perceptions had shorter overall survival (Medians: 22 [Range 10-29] vs 42 [Range 28-Not Reached] months, log-rank p = 0.004). Adjusting for receipt of financial assistance, patients with negative illness perceptions experienced higher risk of death (HR 1.65, 95% CI 1.10-2.48). Conclusions: In this prospective study of CCT participants, we found that patients with negative illness perceptions experienced greater financial toxicity, more symptom burden, and worse survival than those with more positive perceptions, despite comparable sociodemographic/clinical factors. These findings highlight the need to assess and address patients’ illness perceptions and financial burden when seeking to enhance patient-centered outcomes in oncology.

There are many models for sharing clinical-trial data. These investigators provide their viewpoint on why an open-data model has value over others.

In tribute to the origins of the Journal and to those who made, and continue to make, it possible, this editorial looks back at the past 25 years since the first issue of The Oncologist was published.

Background Sub-Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals because of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. Methods In its initial year, 2018, the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of seven fellows for 3-week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants prior to arrival and upon departure; additionally, three participated in semistructured interviews. Results Five themes emerged from the qualitative data: expectations of POETIC, differences between oncology in the U.S. and in sub-Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient-centered care; clinical trials; and collaboration among medical, radiation, and surgical oncologists. From the quantitative data, feedback was primarily around logistical areas for improvement. Conclusion POETIC was found to be feasible and valuable. The results from the pilot year justify the program's continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future research will report on the expansion of the program and follow-up with former participants. Implications for Practice This work presents a novel model for fellowship exchange between lower- and higher-resourced areas. The program is a short-term observership with tumor boards and didactic teaching sessions incorporated. By attracting oncologists who aim to practice in their home countries, it facilitates international collaboration without contributing to the preexisting lack of medical professionals in low- and middle-income countries.

6526 Background: Cancer clinical trial (CCT) participants are at high risk for experiencing adverse effects from financial toxicity, yet this remains understudied in the CCT population. We sought to describe associations among patient-reported financial toxicity (financial burden [FB] and trial cost concerns), physical and psychological symptoms, illness perceptions, and communication confidence in CCT participants. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance and a group of patients matched by age, sex, cancer type, specific trial, and trial phase. We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, and to examine associations of FB and trial cost concerns with patients’ symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) and had lower incomes ( < $100,000, OR 4.61, 95% CI 2.35-9.01). Patients reporting trial cost concerns also had lower incomes ( < $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS total (OR 1.03, 95% CI 1.02-1.05), ESAS physical (OR 1.04, 95% CI 1.02-1.07), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS total (OR 1.03, 95% CI 1.01-1.05), ESAS physical (OR 1.04, 95% CI 1.01-1.06), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptom burden, more negative illness perceptions, and lower communication confidence, which underscores the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.

1065 Background: The GATA3 gene encodes for a transcription factor (TF) that plays a pivotal role in the development of breast tissue. Breast tumors with lower GATA3 expression have worse prognosis compared to tumors with higher expression. However, the consequences of somatic GATA3 mutations ( GATA3mut) on clinical outcomes in metastatic breast cancer (MBC) remain poorly understood. Further, GATA3 TF interferes with FOXA1 and ER to enhance transcription of ER-responsive genes, but the role of GATA3mut in altering downstream transcriptional activity and its effects on response to anti-estrogens remains unclear. Methods: We retrospectively identified ctDNA next-generation sequencing results from 101 ER+/HER2- patients with MBC treated with either selective estrogen receptor degraders (SERDs) alone or a combination of SERDs and CDK4/6 inhibitors at Massachusetts General Hospital (Boston, MA) and Northwestern University (Chicago, IL). Associations between GATA3mut, patient and tumor characteristics, and prior treatments were assessed using logistic regression. Clinical outcomes were estimated through Cox proportional hazards regression. Results: GATA3mut were observed in 13 patients (13%), each with a single GATA3 variant. These mutations were detected in exon 4 (M294K), exon 5 that includes Zn-finger-2 motif (T327fs, R331fs, N334K, D336fs, c.925-3_925-2del splice acceptor variant), and exon 6 (K358fs, P409fs, M416fs, G431fs, M439fs, V440fs). All mutations except for M294K were insertion/deletion frameshift mutations that result in either elongation or truncation of the protein, potentially with heterogenous downstream effects. GATA3mut were the only detectable alteration in 4 patients. The most commonly co-occurring mutations with GATA3mut were ESR1mut in 7/13 (53.8%) and PIK3CAmut in 6/13 (46%) patients. Presence of GATA3mut was associated with prior exposure to chemotherapy (OR = 1.09, 95%CI [1.01 - 1.10], p = 0.03). Patients with GATA3mut tumors had shorter PFS compared to GATA3wild tumors (4.1 vs. 6.7 months, in both univariate and multivariate analysis controlled for presence of ESR1mut: HR = 2.22 95%CI [1.12 – 4.38], p = 0.02). OS was also significantly shorter in patients harboring GATA3mut compared to GATA3wild (14.1 vs. 27.1 months, multivariate analysis: HR = 2.30 95%CI [1.04 – 5.11], p = 0.04). Conclusions: GATA3mut in breast cancer tend to be grouped within exons 5 and 6, and they likely contribute to acquired resistance to endocrine-based therapies in MBC. Our study showed that patients with GATA3mut ER+ MBC have worse prognosis compared to those who were GATA3wild. Larger studies are needed to further stratify and ascertain functional effects of different GATA3 mutations and explore GATA3 gene or its translational product as a possible druggable target.

Low-cost, rapid and accurate detection technologies are key requisites to cope with the growing global cancer challenges. The need is particularly pronounced in resource-limited settings where treatment opportunities are often missed due to the absence of timely diagnoses. We herein describe a Holographic Assessment of Lymphoma Tissue (HALT) system that adopts a smartphone as the basis for molecular cancer diagnostics. The system detects malignant lymphoma cells labeled with marker-specific microbeads that produce unique holographic signatures. Importantly, we optimized HALT to detect lymphomas in fine-needle aspirates from superficial lymph nodes, procedures that align with the minimally invasive biopsy needs of resource-constrained regions. We equipped the platform to directly address the practical needs of employing novel technologies for "real world" use. The HALT assay generated readouts in

This editorial introduces a special series investigating the impact of systemic racism on the health outcomes of minority communities in the United States.

PURPOSE Sub-Saharan Africa is simultaneously facing a rising incidence of cancer and a dearth of medical professionals as a result of insufficient training numbers and emigration, creating a growing shortage of cancer care. To combat this, Massachusetts General Hospital and Beth Israel Deaconess Medical Center partnered with institutions in South Africa, Tanzania, and Rwanda to develop a fellowship exchange program to supplement the training of African oncologists practicing in their home countries. METHODS In its initial 2 years (2018 and 2019), the Program for Enhanced Training in Cancer (POETIC) hosted a pilot cohort of 14 fellows for 3-week observerships in their areas of interest. Researchers distributed questionnaires for program evaluation to participants before arrival and upon departure, and 8 participated in semistructured interviews. RESULTS Five themes emerged from the qualitative data: expectations of POETIC, differences in oncology between the United States and sub-Saharan Africa, positive elements of the program, areas for improvement, and potential impact. Fellows identified several elements of Western health care that will inform their practice: patient-centered care, research development, and collaboration among medical, radiation, and surgical oncologists. The time in Boston modeled a research infrastructure that participants expressed interest in emulating at their home hospitals. In addition, the fellowship inspired some participants to address prevention and survivorship efforts in their home countries. From the quantitative data, feedback was primarily around logistical areas for improvement. CONCLUSION POETIC was found to be feasible and valuable. The results from the first years justify the program’s continuation in hopes of strengthening global health partnerships to support oncology training in Africa. One weakness is the small number of fellows, which will limit the impact of the study and the relevance of its conclusions. Future work will involve long-term follow up with participants and the development of an alumni network.

1062 Background: We assessed the antitumor activity of cabozantinib, a potent multi-receptor oral tyrosine kinase inhibitor with activity against MET, RET, VEGFR2, and AXL, in patients with hormone-receptor positive (HR+) breast cancer with bone metastases. Methods: In this single-arm multicenter phase II study, patients with HR+, HER2- metastatic breast cancer and ≥ 1 prior line of therapy received an initial starting dose of 100 mg cabozantinib, later reduced to 60 mg per day. The primary endpoint was bone scan response rate determined by independent central review and defined as percent change of bone scan area from baseline. The target bone scan response rate was 30% compared to a null response rate of 10%. Secondary endpoints included objective response rate (ORR) by RECIST v1.1, progression free (PFS) and overall survival (OS). Bone scan and CT were obtained every 12 weeks. Results: Among 52 enrolled patients, median age was 55, and 54% and 42% had > 2 lines prior endocrine and chemotherapy, respectively and 18 (35%) had bone-only disease. 20 (38%) experienced a partial bone scan response and 6 (12%) had stable disease (SD). 16 (31%) patients discontinued study prior to week 12 assessment for early clinical progression or toxicity, and three (6%) had missing follow-up scans. Best extra-osseous overall response revealed SD in 26 (50%), but no objective responses. In 25 patients with bone scan disease control at 12 weeks, only 3 (12%) developed extra-osseous progression. Median PFS was 4.3 months (90% CI 2.8 - 5.5) and OS was 19.6 months (90% CI 18.0 – 26.8). In a landmark analysis, patients with bone scan disease control at 12 weeks had longer OS (median 24.2 months, 90% CI 16.4 – 31.7) than those without (median OS 13.3 months, 90% CI 9.5 – 18.2), with a hazard ratio of 0.37 (90% CI 0.21 – 0.65). Most common grade 3 or 4 toxicities were hypertension (10%), anorexia (6%), diarrhea (6%), fatigue (4%) and hypophosphatemia (4%). Dose reduction or delay occurred in 42 (81%) patients. Conclusions: This study met its primary endpoint with bone scans improved in 38% of patients with metastatic HR+ breast cancer and remained stable in an additional 12% with cabozantinib treatment. Bone scan response correlated with improved OS. This is the first reported study in breast cancer to use bone scan response as a primary endpoint. Further studies with cabozantinib in HR+ breast cancer and additional validation of bone scan response as a surrogate for clinical benefit in breast cancer are warranted. Clinical trial information: NCT01441947 .

e19062 Background: Ethnic/racial minorities and socioeconomically disadvantaged patients remain underrepresented in cancer clinical trials (CCT), challenging the accuracy and generalizability of findings. While oncologists’ recommendations influence trial participation, we know little about their perspectives on recommending CCT to underrepresented patients. Methods: From 9/16-5/19 we conducted a sequential mixed methods study to assess oncologists’ attitudes toward recommending underrepresented patients for CCT. We performed individual interviews with 17 oncologists, developed a survey instrument, and surveyed a randomly selected sample of 98 oncologists (from ASCO, NCORP, MGH; RR = 31.2%). Descriptive statistics summarized attitudes, practices and challenges with trial enrollment of underrepresented patients. Results: Content analysis of interviews (age = 46.9, female = 37.5%, white = 75.0%) revealed overall support for CCT. Indeed, 84.4% of survey respondents (age = 53.3, female = 31.3%, white = 78.6%) considered CCT as central to their professional identity. Yet, 37.5% agreed CCT placed undue burden on oncologists. Oncologists’ concerns around informed consent and perceived lack of clinical/personal equipoise discouraged recommending CCT participation to vulnerable patients. Interviews revealed that nearly all believed that patients with certain vulnerabilities (e.g., literacy, social, financial barriers) had needs that conflicted with CCT demands, increasing the potential for harm. Oncologists were less likely to recommend CCT to patients who do not reliably report side effects (91.2%), demonstrate difficulty comprehending the costs/benefits of CCT (88.7%), lack support (87.6%), live far away (76.3%), or face insurance obstacles (73.2%). Notably, 67.7% affirmed they presented trials with varying enthusiasm based on perceived patient challenges; 32.4% deemed it hard to justify enrolling patients if efficacious standard treatment options exist outside of trials. Oncologists desired navigation support (63.3%) to offset concerns and facilitate trial discussion/enrollment. Conclusions: Findings confirm that oncologists value CCT; however, they experience conflict when considering CCT for patients with pre-existing hardships. Time constraints interfere with oncologists’ ability to adequately address and overcome perceived challenges to participation. Our findings underscore the need for programs that integrate informational support with patient navigation to increase enrollment of underrepresented patients into CCT.

Reflections on the career and accomplishments of Professor Patrick G. Johnston, who is still greatly missed.

The cause of drug shortages is a complex issue. This commentary highlights the shortage of intravenous opioid medications for cancer patients, in light of the opioid overdose epidemic.

Immuno-oncology has been heralded as a breakthrough cancer treatment, and Chinese researchers have emerged as important contributors to this area of research. The Immuno-Oncology Special Issue highlights articles by researchers in China, focusing on immunotherapy for various cancer types from different perspectives for the benefit of our readers.

RAS mutations are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors and around a fifth of common myeloid malignancies, but they have evaded therapeutic interventions, despite being the focus of intense research over the last three decades. Recent discoveries lend new understanding about the structure, function, and signaling of RAS and have opened new avenues for development of much needed new therapies. We discuss the various approaches under investigation to target mutant RAS proteins. The recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Multiple clinical trials targeting synthetically lethal partners and/or downstream signaling partners of RAS are underway. Novel inhibitors targeting various arms of RAS processing and signaling have yielded encouraging results in the laboratory, but refinement of the drug-like properties of these molecules is required before they will be ready for the clinic.

BACKGROUND Patient adherence to appointments is key to improving outcomes in health care. “No-show” appointments contribute to suboptimal resource use. Patient navigation and telephone reminders have been shown to improve cancer care and adherence, particularly in disadvantaged populations, but may not be cost-effective if not targeted at the appropriate patients. METHODS In 5 clinics within a large academic cancer center, patients who were considered to be likely (the top 20th percentile) to miss a scheduled appointment without contacting the clinic ahead of time (“no-shows”) were identified using a predictive model and then randomized to an intervention versus a usual-care group. The intervention group received telephone calls from a bilingual patient navigator 7 days before and 1 day before the appointment. RESULTS Over a 5-month period, of the 40,075 appointments scheduled, 4425 patient appointments were deemed to be at high risk of a “no-show” event. After the patient navigation intervention, the no-show rate in the intervention group was 10.2% (167 of 1631), compared with 17.5% in the control group (280 of 1603) (P

Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several other agents are in advanced stages of clinical development, including sacituzumab govitecan for breast cancer, mirvetuximab soravtansine for ovarian cancer, rovalpituzumab tesirine for lung cancer, depatuxizumab mafodotin for glioblastoma, and oportuzumab monatox for bladder cancer. This review provides an overview of the recent clinical experience with the approved, most advanced, and other promising candidates of ADCs for solid tumors, including a description of biology and chemistry of ADCs, drug resistance and biomarkers, and the future perspective on combination strategies with these new immunoconjugates.

The rapid evolution of our understanding of cancer biology has affected every phase of patient management, from early detection to drug development and clinical management. Central to this issue is the challenge of using biomarkers to identify the driving mutations present and identifiable by current assays in many tumors. These biomarkers are integral to the process of selecting patients for the testing of new drugs, many of which are specifically designed to inhibit oncogenic pathways.

A case of severe hepatic toxicity associated with the use of kratom, a plant derivative increasingly used as a psychostimulant, is discussed.

Reflections on the life and legacy of Patrick G. Johnston, the President and Vice Chancellor of Queen's University Belfast, a Senior Editor of The Oncologist, and friend.