An Assessment of the Feasibility and Utility of an ACCC-ASCO Implicit Bias Training Program to Enhance Racial and Ethnic Diversity in Cancer Clinical Trials.

PURPOSE: Cancer trial participants do not reflect the racial and ethnic diversity in the population of people with cancer in the United States. As a result of multiple system-, patient-, and provider-level factors, including implicit bias, cancer clinical trials are not consistently offered to all potentially eligible patients. MATERIALS AND METHODS: ASCO and ACCC evaluated the utility (pre- and post-test knowledge changes) and feasibility (completion rates, curriculum satisfaction metrics, survey questions, and interviews) of a customized online training program combined with facilitated peer-to-peer discussion designed to help research teams identify their own implicit biases and develop strategies to mitigate them. Discussion focused on (1) specific elements of the training modules; (2) how to apply lessons learned; and (3) key considerations for developing a facilitation guide to support peer-to-peer discussions in cancer clinical research settings. We evaluated discussion via a qualitative assessment. RESULTS: Participant completion rate was high: 49 of 50 participating cancer programs completed training; 126 of 129 participating individuals completed the training (98% response rate); and 119 completed the training and evaluations (92% response rate). Training increased the mean percentage change in knowledge scores by 19%-45% across key concepts (eg, causes of health disparities) and increased the mean percentage change in knowledge scores by 10%-31% about strategies/actions to address implicit bias and diversity concerns in cancer clinical trials. Knowledge increases were sustained at 6 weeks. Qualitative evaluation validated the utility and feasibility of facilitated peer-to-peer discussion. CONCLUSION: The pilot implementation of the training program demonstrated excellent utility and feasibility. Our evaluation affirms that an online training designed to raise awareness about implicit bias and develop strategies to mitigate biases among cancer research teams is feasible and can be readily implemented in cancer research settings.

Increasing Racial and Ethnic Diversity in Cancer Clinical Trials: An American Society of Clinical Oncology and Association of Community Cancer Centers Joint Research Statement.

A concerted commitment across research stakeholders is necessary to increase equity, diversity, and inclusion (EDI) and address barriers to cancer clinical trial recruitment and participation. Racial and ethnic diversity among trial participants is key to understanding intrinsic and extrinsic factors that may affect patient response to cancer treatments. This ASCO and Association of Community Cancer Centers (ACCC) Research Statement presents specific recommendations and strategies for the research community to improve EDI in cancer clinical trials. There are six overarching recommendations: (1) clinical trials are an integral component of high-quality cancer care, and every person with cancer should have the opportunity to participate; (2) trial sponsors and investigators should design and implement trials with a focus on reducing barriers and enhancing EDI, and work with sites to conduct trials in ways that increase participation of under-represented populations; (3) trial sponsors, researchers, and sites should form long-standing partnerships with patients, patient advocacy groups, and community leaders and groups; (4) anyone designing or conducting trials should complete recurring education, training, and evaluation to demonstrate and maintain cross-cultural competencies, mitigation of bias, effective communication, and a commitment to achieving EDI; (5) research stakeholders should invest in programs and policies that increase EDI in trials and in the research workforce; and (6) research stakeholders should collect and publish aggregate data on racial and ethnic diversity of trial participants when reporting results of trials, programs, and interventions to increase EDI. The recommendations are intended to serve as a guide for the research community to improve participation rates among people from racial and ethnic minority populations historically under-represented in cancer clinical trials. ASCO and ACCC will work at all levels to advance the recommendations in this publication.

The Effect of Disclosing Life Expectancy Information on Patients' Prognostic Understanding: Secondary Outcomes From a Multicenter Randomized Trial of a Palliative Chemotherapy Educational Intervention.

CONTEXT: Many advanced patients with cancer have unrealistic prognostic expectations. OBJECTIVES: We tested whether offering life expectancy (LE) statistics within palliative chemotherapy (PC) education promotes realistic expectations. METHODS: In this multicenter trial, patients with advanced colorectal and pancreatic cancers initiating first or second line PC were randomized to usual care versus a PC educational tool with optional LE information. Surveys at two weeks and three months assessed patients' review of the LE module and their reactions; at three months, patients estimated their LE and reported occurrence of prognosis and end-of-life (EOL) discussions. Wilcoxon tests and proportional odds models evaluated between-arm differences in LE self-estimates, and how realistic those estimates were (based on cancer type and line of treatment). RESULTS: From 2015 to 2017, 92 patients were randomized to the intervention and 94 to usual care. At baseline most patients (80.9%) wanted "a lot" or "as much information as possible" about the impact of chemotherapy on LE. Among patients randomized to the intervention, 52.0% reviewed the LE module by two weeks and 66.7% by three months-of whom 88.2% reported the information was important, 31.4% reported it was upsetting, and 3.9% regretted reviewing it. Overall, patients' LE self-estimates were very optimistic; 71.4% of patients with colorectal cancer estimated greater than five years; 50% pancreatic patients estimated greater than two years. The intervention had no effect on the length or realism of patients' LE self-estimates, or on the occurrence of prognostic or EOL discussions. CONCLUSIONS: Offering LE information within a PC educational intervention had no effect on patients' prognostic expectations.

Effectiveness of a Multimedia Educational Intervention to Improve Understanding of the Risks and Benefits of Palliative Chemotherapy in Patients With Advanced Cancer: A Randomized Clinical Trial.

Importance: Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote. Objective: To determine whether a PC educational video and booklet at treatment initiation could improve patients' understanding of its benefits and risks. Interventions: Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review. Design, Setting, and Participants: Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019. Main Outcomes and Measures: The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding "not at all likely" to "What is your understanding of how likely the chemotherapy is to cure your cancer?" (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy-General emotional well-being subscale). Results: Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted "a lot" of information or "as much information as possible" about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar. Conclusions and Relevance: Provision of an educational video and booklet did not alter patients' expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02282722.

Phase 1 Study of Neoadjuvant Short-Course Radiation Therapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer.

PURPOSE: To assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer. METHODS AND MATERIALS: Patients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX. To mitigate the potential added toxicity from concurrent 5-FU, intensity modulated RT was used. Using the continual reassessment method, the dose of 5-FU was escalated from 100 to a maximum-tolerated dose of 200 mg/m2/d. RESULTS: Fourteen patients were accrued. All patients completed continuous infusion 5-FU and short-course RT and the 5-FU dose was safely escalated to 200 mg/m2/d with no dose-limiting toxicity. Thirteen patients received the neoadjuvant mFOLFOX, and only 1 patient went straight to surgery after chemoradiation. Clinical response was 21% complete, 63% partial, 14% stable disease, and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 64% partial response and 14% stable disease. No patients had pathologic progression. The most common grade 3 and 4 toxicities were cytopenias. The most common grade 1 and 2 toxicities were cytopenia, fatigue, diarrhea, and nausea. CONCLUSIONS: Our findings suggest that concurrent chemotherapy with neoadjuvant short-course RT is feasible and can be safely given with concurrent continuous infusion 5-FU. This works adds to the growing evidence that short-course RT is not only equivalent to long-course RT, but also may provide additional benefits, such as allowing for a transition to full dose systemic therapy in the neoadjuvant setting, selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic RT.

Patient access to clinical notes in oncology: A mixed method analysis of oncologists' attitudes and linguistic characteristics towards notes.

BACKGROUND: Providers have expressed concern about patient access to clinical notes. There is the possibility that providers may linguistically censor notes knowing that patients have access. PURPOSE: Qualitative interviews and a pre- and post- linguistic analysis of the implementation of OpenNotes was performed to determine whether oncologists changed the content and style of their notes. METHODS: Mixed methods were utilized, including 13 semi-structured interviews with oncologists and random effects modeling of over 500 clinical notes. The Linguistic Inquiry and Word Count program was used to evaluate notes for emotions, thinking styles, and social concerns. RESULTS: No significant differences from pre- and post-implementation of OpenNotes was found. Thematic analysis revealed that oncologists were concerned that changing their notes would negatively impact multidisciplinary communication. However, oncologists acknowledged that notes could be more patient-friendly and may stimulate patient-provider communication. CONCLUSIONS: Although oncologists were aware that patients could have access, they felt strongly about not changing the content of notes. A comparison between pre- and post-implementation confirmed this view and found that notes did not change. PRACTICE IMPLICATIONS: Patient access to oncologist's notes may serve as an opportunity to reinforce important aspects of the consultation.

Adjuvant radiation therapy for T4 non-rectal colon adenocarcinoma provides a cause-specific survival advantage: A SEER database analysis.

PURPOSE: While there is no level 1 evidence supporting the use of adjuvant radiotherapy (RT) for non-rectal colon cancer in the modern chemotherapy era, there are studies that suggest a local control benefit. This treatment modality is not part of standard treatment recommendations, and we hypothesized that adjuvant RT provides a benefit in locally advanced disease. Due to the limited number who receive post-operative RT, a national database was searched to provide sufficient power. MATERIALS AND METHODS: A retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database was performed. Inclusion criteria were: non-rectal colon cancer, AJCC 6th or 7th edition T4 and M0, oncologic resection, and 1st cancer site. Patients were excluded for RT prior to or during surgery, or if the sequence of RT was unknown. Using a Cox proportional hazard model, the relative risk of cause-specific mortality for "RT after surgery" versus "No RT" was calculated. RESULTS: 21,789 patients were identified who met the inclusion criteria. Of these, only 1001 received adjuvant RT, and 64% were node-positive (53% RT vs. 65% no RT). When comparing RT vs. no RT, after adjusting for sex, age, N stage, and grade, we determined the relative risk of death from cancer was 0.8849 (95% CI: 0.8008-0.9779; p = 0.0165), suggesting that only 14 patients with T4 disease need receive adjuvant radiation to spare a cancer-related death. CONCLUSIONS: Adjuvant RT is not routinely utilized for definitive treatment of T4 non-rectal colon cancer, but this analysis shows a significant cause-specific survival benefit.

OpenNotes in oncology: oncologists' perceptions and a baseline of the content and style of their clinician notes.

Patients' ability to access their provider's clinical notes (OpenNotes) has been well received and has led to greater transparency in health systems. However, the majority of this research has occurred in primary care, and little is known about how patients' access to notes is used in oncology. This study aims to understand oncologists' perceptions of OpenNotes, while also establishing a baseline of the linguistic characteristics and patterns used in notes. Data from 13 in-depth, semistructured interviews with oncologists were thematically analyzed. In addition, the Linguistic Inquiry and Word Count (LIWC) program evaluated over 200 clinician notes, measuring variables encompassing emotions, thinking styles, social concerns, and parts of speech. Analysis from LIWC revealed that notes contained negative emotional tone, low authenticity, high clout, and high analytical writing. Oncologists' use of stigmatized and sensitive words, such as "obese" and "distress," was mainly absent. Themes from interviews revealed that oncologists were uncertain about patients' access to their notes and may edit their notes to avoid problematic terminology. Despite their reluctance to embrace OpenNotes, they envisioned opportunities for an improved patient-provider relationship due to patients initiating interactions from viewing notes. Oncologists believe notes are not intended for patients and altering their content may compromise the integrity of the note. This study established a baseline for further study to compare notes pre-implementation to post-implementation. Further analysis will clarify whether oncologists are altering the style and content of their notes and determine the presence of patient-centered language.

Identifying How Patient Portals Impact Communication in Oncology.

Patient portals are becoming widespread throughout health-care systems. Initial research has demonstrated that they positively impact patient-provider communication and patients' health knowledge, but little is known about the impact of patient portals in the cancer setting, where highly complex and uncertain medical data are available for patients to view. To better understand communicative behaviors and perceptions of the patient portal and how it is utilized in oncology, in-depth, semi-structured interviews were conducted with 48 participants: 35 patients and 13 oncologists. Thematic analysis identified that portals help to enhance participation during in-person consultations, increase patients' self-advocacy, and build rapport with providers. However, patients' comfort level with reviewing information via the portal depended upon the severity of the test. Oncologists worried about patient anxiety and widening health disparities, but acknowledged that the portal can motivate them to expedite communication about laboratory and scan results. As patient portals become more widely used in all medical settings, oncologists should become more engaged with how patients are viewing their medical information and consider the portal within the framework of patient-centered care by valuing patients' communication preferences.

Implications of Patient Portal Transparency in Oncology: Qualitative Interview Study on the Experiences of Patients, Oncologists, and Medical Informaticists.

BACKGROUND: Providing patients with unrestricted access to their electronic medical records through patient portals has impacted patient-provider communication and patients' personal health knowledge. However, little is known about how patient portals are used in oncology. OBJECTIVE: The aim of this study was to understand attitudes of the portal's adoption for oncology and to identify the advantages and disadvantages of using the portal to communicate and view medical information. METHODS: In-depth semistructured interviews were conducted with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists. Interviews were recorded, transcribed, and thematically analyzed to identify critical incidents and general attitudes encountered by participants. RESULTS: Two primary themes were discovered: (1) implementation practices influence attitudes, in which the decision-making and execution process of introducing portals throughout the hospital did not include the input of oncologists. Lack of oncologists' involvement led to a lack of knowledge about portal functionality, such as not knowing the time period when test results would be disclosed to patients; (2) perceptions of portals as communication tools varies by user type, meaning that each participant group (patients, oncologists, and medical informaticists) had varied opinions about how the portal should be used to transmit and receive information. Oncologists and medical informaticists had difficulty understanding one another's culture and communication processes in their fields, while patients had preferences for how they would like to receive communication, but it largely depended upon the type of test being disclosed. CONCLUSIONS: The majority of patients (54%, 19/35) who participated in this study viewed lab results or scan reports via the portal before being contacted by a clinician. Most were relatively comfortable with this manner of disclosure but still preferred face-to-face or telephone communication. Findings from this study indicate that portal education is needed for both patients and oncologists, especially when portals are implemented across entire health systems since highly specialized areas of medicine may have unique needs and uses. Patient portals in oncology can potentially alter the way diagnoses are delivered and how patients and oncologists communicate. Therefore, communication about the portal should be established during initial consultations so patients can decide whether they want to be informed in such a manner.

Phase II study of docetaxel and gefitinib as second-line therapy in gemcitabine pretreated patients with advanced pancreatic cancer.

BACKGROUND: There is no standard second-line therapy for advanced pancreatic cancer (APC). We evaluated the epidermal growth factor receptor (EGFR) inhibitor gefitinib and docetaxel in a phase II study following gemcitabine failure. METHODS: EGFR overexpression was not required. The initial docetaxel dose was 75 mg/m(2) on day 1 every 21 days. Due to febrile neutropenia in 8 of the first 18 patients, the dose was reduced to 60 mg/m(2). Gefitinib, 250 mg/day orally, was given continuously. RESULTS: Forty-one patients received treatment and were evaluable. Febrile neutropenia was seen in 11 patients (27%), with most events occurring at the docetaxel dose of 75 mg/m(2) (8 of 18 patients). Common treatment-related grade 3/4 toxicities were: fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). There was 1 partial response and stable disease in 19 patients. Time to progression was 1.8 months and median survival was 4.5 months (95% CI 2.9-5.7). CONCLUSION: The tolerability and feasibility of second-line therapy for APC was demonstrated. The combination of gefitinib and docetaxel showed evidence of limited efficacy.

Phase II study of rubitecan, an oral camptothecin in patients with advanced colorectal cancer who have failed previous 5-fluorouracil based chemotherapy.

BACKGROUND: Rubitecan (RFS-2000, 9NC, Orathecin) is an orally bioavailable camptothecin analogue, with evidence of preclinical activity in colon cancer cell lines. We evaluated oral rubitecan (5 days on, 2 days rest per week) on a continuous schedule, in patients with advanced colorectal cancer (CRC), who progressed after 5-fluorouracil based chemotherapy. PATIENTS AND RESULTS: Fourteen eligible patients were treated with rubitecan at 1.5 mg/m2/day on a 5 day/week continuous schedule. Therapy was well tolerated with most adverse events in the mild to moderate category. Grade 3/4 toxicity consisting of anemia, diarrhea and elevated bilirubin was seen in 4 patients. No responses were seen in 13 evaluable patients. Overall median survival (95% confidence interval) was 10.1 (range 3.1-12.6) months, and median time to progression was 2.1 months. CONCLUSIONS: Administration of rubitecan was well tolerated, but this schedule does not appear to have clinical activity in patients with advanced previously treated CRC.

A phase I/II study of trimetrexate and capecitabine in patients with advanced refractory colorectal cancer.

OBJECTIVE: We tested the hypothesis that the combination of trimetrexate (TMTX) and capecitabine (CAP) would be active in patients with previously treated metastatic colorectal cancer (CRC). Because the optimum dose of this combination was unknown, we used a phase I/II design. METHODS: In the phase I cohort, patients received 110 mg/m2 TMTX intravenously weekly x6 and CAP starting at 750 mg/m2 orally twice daily from days 2 to 15 and 23 to 36 (one cycle). Cycles were repeated every 8 weeks. The phase II doses were 110 mg/m2 TMTX and 1000 mg/m2 CAP orally twice daily. RESULTS: Thirty-two patients were entered. All patients had prior 5-fluorouracil therapy and 94% had prior exposure to irinotecan. Grade 3/4 toxicities included abdominal pain in 4 patients (12.5%) and vomiting in 3 patients (9.4%). Twenty-seven patients were evaluable for response: one patient each had a complete response and a partial response for an overall response rate of 7.4%. The median time to progression was 3.3 months (95% confidence interval [CI], 1.6-3.7 months) and the median overall survival was 5.9 months (95% CI, 5.2-10.2 months). CONCLUSIONS: The combination of TMTX and CAP is well tolerated. However, recent studies have shown more active regimens in the second- and third-line metastatic setting.

Phase I and pharmacokinetic study of vinblastine and high-dose megestrol acetate.

PURPOSE: Preclinical data indicate that progestational agents (progesterone, medroxyprogesterone acetate and megestrol acetate) interact with p-glycoprotein (P-gp) and reverse P-gp-associated resistance to vinca alkaloids and other natural products. Based on these data, we performed a phase I study of high-dose oral megestrol acetate and vinblastine to evaluate the safety of this regimen. PATIENTS AND METHODS: Enrolled in the study were 61 patients with advanced solid tumors, refractory to standard therapy. Cohorts of patients received megestrol acetate according to the following escalation scheme (loading dose/maintenance dose, twice daily for 7 days): 750 mg/250 mg, 750 mg/375 mg, 1000 mg/500 mg, 1500 mg/1000 mg, 3000 mg/2000 mg, 4500 mg/3000 mg, 6000 mg/4000 mg, and 7500 mg/5000 mg. They also received 1.5 mg/m(2) per day of vinblastine by continuous infusion for 5 days (days 2 to 6). RESULTS: Of the 61 patients, 59 were evaluable for toxicity. A maximum tolerated dose (MTD) was not reached. The regimen was well tolerated. Of the 59 patients, 10 (17%) experienced grade 4 leukopenia. All of these cases were at dose levels 3 to 8. There was an increase in the steady-state concentration (Css) of megestrol acetate with increasing dose up to the sixth dose level. Further increases in the dose produced no change in the megestrol acetate Css. Only 2.4% of megestrol acetate was free in the plasma as compared to 65.6% in RPMI culture medium. Megestrol acetate administration was associated with profound suppression of ACTH and cortisol levels. CONCLUSIONS: The combination of vinblastine and megestrol acetate was well tolerated. An MTD for this combination was not achieved as a result of the saturable absorption of megestrol acetate. Although potentially therapeutic serum concentrations of megestrol acetate were achieved, it is unlikely that MDR was reversed given the high protein-binding of the drug. Profound suppression of the pituitary-adrenal axis was also observed during the administration of megestrol acetate.