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Background More than half of the 40,000 incident rectal cancer patients in the United States each year are diagnosed at clinical stage II and III (locally advanced stage). For this group, high rates of cure can be achieved with the combination of pelvic radiation and sensitizing 5-fluorouracil (chemoradiation), surgery and chemotherapy, but treatment is long, arduous and toxicities are substantial. The PROSPECT trial (N1048, NCT01515787) was designed to determine whether neoadjuvant chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX) could be used as an alternative to neoadjuvant chemoradiation without compromising treatment outcomes and to spare these patients excess toxicity. The statistical design balanced the twin co-primary goals of achieving low local and distant recurrence rates. Study design features contended with the need for stringent safeguards given limited phase II data, the need for straightforward criteria to facilitate both accrual and protocol fidelity and the importance of patients’ perspectives on symptom burden and treatment toxicity. Methods PROSPECT is an ongoing multi-site two-group seamless phase II/III randomized trial comparing standard neoadjuvant chemoradiation versus neoadjuvant chemotherapy with selective use of chemoradiation for patients with locally advanced rectal cancer. Challenges addressed in the design and conduct of PROSPECT have included the following: (1) setting safety thresholds given limited single-center phase II data, (2) establishing workable eligibility criteria, (3) balancing competing time to local and distant recurrence as co-primary endpoints and (4) obtaining reliable and complete data for patients’ symptom burden. The design and implementation challenges, choices, modifications and their implications for the design of future national cooperative group clinical trials are presented. Results PROSPECT incorporated stringent thresholds for both complete surgical resection (R0) and the time to local recurrence as early stopping rules. When predetermined stopping criteria were not met after evaluation of the first 366 participants in the randomized phase II, the study transitioned seamlessly to phase III with cumulative accrual of over 1000 participants. Eligibility criteria stipulating rectal tumor location based on distance from the anal verge were unworkable, and the protocol was amended to a more pragmatic approach that assigned surgeons with primary responsibility for determining eligibility. Central radiology review was feasible and in some cases prompted discontinuation of protocol treatment. Participation in toxicity reporting using the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events was uniformly high and was well accepted by participants from over 200 sites in the United States, Canada and Switzerland. Conclusion The strategies used to overcome these obstacles may inform the design of other studies that involve multi-modality treatment interventions, particularly trials where implementation of consistent criteria for eligibility and outcomes across hundreds of practice settings is necessary.

Abstract Objective The study sought to describe patient-entered supplemental information on symptomatic adverse events (AEs) in cancer clinical research reported via a National Cancer Institute software system and examine the feasibility of mapping these entries to established terminologies. Materials and Methods Patients in 3 multicenter trials electronically completed surveys during cancer treatment. Each survey included a prespecified subset of items from the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Upon completion of the survey items, patients could add supplemental symptomatic AE information in a free text box. As patients typed into the box, structured dropdown terms could be selected from the PRO-CTCAE item library or Medical Dictionary for Regulatory Activities (MedDRA), or patients could type unstructured free text for submission. Results Data were pooled from 1760 participants (48% women; 78% White) who completed 8892 surveys, of which 2387 (26.8%) included supplemental symptomatic AE information. Overall, 1024 (58%) patients entered supplemental information at least once, with an average of 2.3 per patient per study. This encompassed 1474 of 8892 (16.6%) dropdowns and 913 of 8892 (10.3%) unstructured free text entries. One-third of the unstructured free text entries (32%) could be mapped post hoc to a PRO-CTCAE term and 68% to a MedDRA term. Discussion Participants frequently added supplemental information beyond study-specific survey items. Almost half selected a structured dropdown term, although many opted to submit unstructured free text entries. Most free text entries could be mapped post hoc to PRO-CTCAE or MedDRA terms, suggesting opportunities to enhance the system to perform real-time mapping for AE reporting. Conclusions Patient reporting of symptomatic AEs using a text box functionality with mapping to existing terminologies is both feasible and informative.

158 Background: There is limited research on methods for alerting clinicians to concerning patient-reported outcome (PRO) responses and how often PROs trigger alerts to nurses during cancer care. Methods: In two randomized trials, adults with advanced cancer receiving chemotherapy were enrolled. Participants were randomized to usual care vs. weekly PROs completed between visits (with automated feedback to nurses). PRO responses in the intervention arm triggered automated email alerts to nurses for frequent, severe, or worsening symptoms in the last 7 days. Alert thresholds for PROs were chosen a priori but were unique to each study. The “Symptom Tracking and Reporting” (STAR) trial was conducted at one academic medical center. The “PROs to Enhance Cancer Treatment” (PRO-TECT [AFT-39]) cluster-randomized trial is being conducted in > 30 community practices. Results: In STAR, 766 patients participated (58% female, 38% ages ≥65, 17% minority, 28% ≤high school). 441 participants were randomized to the intervention arm, where 1,431/84,212 items (2%) triggered a concerning symptom alert, during 1,070/8,498 weeks (13%). Frequent alerts were for fatigue (62%), pain (32%), and appetite (16%). In PRO-TECT (AFT-39), 300 patients have been enrolled (58% female, 49% ages ≥65, 8% minority, 47% ≤high school) out of 1,000. 146 participants have been randomized to the intervention arm, where 1,422/24,739 items (6%) triggered an alert, during 824/2249 weeks (37%). Common alerts were for pain (48%), physical function (35%), and diarrhea (15%). PRO-TECT provided clinical decision support with alerts. Conclusions: In two randomized trials in advanced cancer, PROs collected during care delivery enabled tailored treatment based on issues identified on PROs. Pain, physical function, appetite, and diarrhea commonly triggered alerts for concerning symptoms. Early PRO-TECT results are showing a trend for higher weekly alert rates for concerning symptoms (37% vs. 13% in STAR), which may indicate that the PRO intervention will be even more effective in community practices. Results assist in addressing logistical considerations for implementing PROs into routine care. Clinical trial information: NCT03249090.

Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute–sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.

e21681 Background: Maintaining quality of life with minimal symptoms is an important goal of cancer treatment. We surveyed patients undergoing cancer treatment about their preferences for information about the long-term symptom burden associated with their current treatment. Methods: Patients undergoing active cancer treatment were enrolled at two large cancer centers from 1/2014 to 7/2015. At the time of enrollment patients reported their household income, employment, performance status and their agreement with the statement, “It would be useful to know the percentage of patients having persistent symptoms more than a year after getting the same treatment I am getting.” Treatment intention (curative vs. palliative) was reported by the treating oncologist. Results: 196 patients completed the survey. The mean age was 55.7 (range 20-80); 54% were female, 69% were white, and 60% were receiving palliative treatment. The majority (83%) of patients either strongly agreed or somewhat agreed that it would be helpful to have information about future symptoms. In univariable analyses, this preference did not significantly differ based on patient-reported performance status, sex, age, treatment intent, race, or household income. Using a more stringent criterion to dichotomize the outcome, 59% of participants strongly agreed that it would be helpful to have information about future symptoms. Patients undergoing treatment with curative intent were significantly more likely to strongly agree (72% vs. 51%, p = 0.0035). In a multivariable analysis adjusting for age, sex, income level, employment status, and patient-reported performance status, participants undergoing curative versus palliative treatment had 3.1 times the odds (95% CI 1.47-6.65) of strongly agreeing. Conclusions: The majority of patients undergoing cancer treatment wanted to know what symptoms to expect in the future, and this was independent of patient demographics. Patients undergoing treatment with curative intent are significantly more likely to want this information than patients undergoing palliative treatment. Symptom data collected through research studies and registries should be summarized by treatment and other key predictors and made available to patients.