Citations

AbstractIgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL−1 with 19% of patients presenting with levels >6,000 mg dL−1. International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.

432 Background: In clinical trials and clinical practice, tumor response assessment with computed tomography (CT) defines critical end points in patients with metastatic disease treated with systemic agents. Methods to reduce errors and improve efficiency in tumor response assessment could improve patient care. Methods: Eleven readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria using paired baseline and initial post-therapy CT studies from 20 randomly selected patients with metastatic renal cell carcinoma treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard-of-care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error-identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data/image archival. A cross-over design, patient randomization, and two-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. Results: The standard-of-care method was on average associated with one or more errors in 30.5% (6.1/20) of patients while CARE had a 0.0% (0.0/20) error rate (p<0.001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range 1-3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 vs. 13.1 minutes, p<0.001). Conclusions: Computer-assisted tumor response evaluation reduced errors and time of evaluation, indicating better overall effectiveness than manual tumor response evaluation methods that are the current standard-of-care.

764 Background: Psychosocial distress screening and assessment in patients with gastrointestinal (GI) cancers has an established importance due to the distress experienced during and post treatment. GI cancer patients receiving radiotherapy (RT) for curative or palliative measures were reviewed in order to determine if there was a relationship between patient reported distress (PRD) and survival. Methods: Patients at our institution who receive external beam RT for GI cancers completed a 30 question PRD survey that also included a linear analog measure of overall distress, the National Comprehensive Cancer Network (NCCN) Distress Thermometer, which ranged from 1 (low overall distress) to 10 (high overall stress) at the start of and/or during treatment. Each question on the PRD questionnaire concentrated on a possible cause of distress. It allowed patients to rate distress levels for each question from 1 to 5 (1 being the least distressed and 5 being the most distressed), and also overall distress according. The reported clinical results of the PRD questionnaire were retrospectively reviewed in patients receiving RT for GI cancers from Jan 2012 to Aug 2015. Patients were considered distressed if their overall PRD score was 5 or greater (PRD+) or not distressed (PRD-) if their score was 4 or under. Overall survival between PRD+ and PRD- was compared using the Kaplan-Meier method. Results: PRD surveys were completed by 134 consecutive patients, 67 (50%) male and 67 (50%) female within 30 days of starting RT. The median age was 65 years (range 28 to 93). The top histological finding was adenocarcinoma, 90 patients (60%). 113 (84%) received chemotherapy and 64 (48%) underwent surgery. 102 (75%) treatments were curative and 32 (25%) were palliative. Overall NCCN distress thermometer results ranged from 0 to 10, with a median of 4. Median follow-up was 2.7 years. Distressed patients (PRD+) had inferior survival to those not distressed (PRD-) at 2 years, 52% vs. 72%, p<0.02. Conclusions: Patient reported distress is associated with an inferior survival in patients receiving radiotherapy for gastrointestinal tumors.

The optimal surveillance for patients with resected high-risk melanoma is controversial. Select locoregional or oligometastatic recurrences can be cured with salvage resection. Data on the ability of PET/CT to detect such recurrences are sparse. We evaluated whether surveillance PET/CT in patients with resected stage III–IV melanoma led to detection of clinically occult recurrences amenable to curative-intent salvage treatment. We retrospectively identified 1429 melanoma patients who underwent PET/CT between January 2008 and October 2012 at Mayo Clinic (Rochester, Minnesota). A total of 1130 were excluded because of stage I–II, ocular or mucosal melanoma, incomplete resection, PET/CT not performed for surveillance or performed at a different institution, and records not available. A total of 299 patients were eligible. Overall, 162 (52%) patients developed recurrence [locoregional: 77 (48%), distant: 85 (52%)]. The first recurrence was clinically occult in 98 (60%) and clinically evident in 64 (40%). Clinically evident recurrences were more often superficial (skin, subcutaneous, or nodal) or in the brain, whereas clinically occult recurrences more often visceral. Overall, 90% of all recurrences were detected by 2.8 years. In all, 70% of patients with recurrence underwent curative-intent salvage treatment (locoregional: 94%, distant: 48%), with similar rates for clinically occult versus clinically evident recurrences (66 vs. 75%, P=0.240). Overall survival was superior among those who underwent curative-intent salvage treatment [5.9 vs. 1.2 years; hazard ratio=4.27, 95% confidence interval (CI)=2.68–6.80; P<0.001], despite 79% developing recurrence again. PET/CT had high sensitivity (88%, 95% CI=79.94–93.31%), specificity (90%, 95% CI=88.56–91.56%), and negative predictive value (99%, 95% CI=98.46–99.52%). However, the positive predictive value was only 37% (95% CI=31.32–43.68%). In patients with resected stage III–IV melanoma, surveillance PET/CT detected a large proportion of clinically occult recurrences amenable to curative-intent salvage treatment. Despite a high rate of second relapse, curative-intent salvage treatment was associated with superior overall survival. Even though PET/CT had high sensitivity, specificity, and negative predictive value, positive predictive value was poor, highlighting the need for histologic confirmation of PET/CT-detected abnormalities.

Abstract Estrogen receptor positive (ER+) breast cancer accounts for the majority of breast cancers diagnosed worldwide but fortunately, outcomes are markedly improved by pharmacological interventions that interrupt ER function. Unfortunately, suppression of relapse risk from early stage disease with endocrine therapy (anti-estrogens or aromatase inhibitors) is only ∼50%, and for advanced disease, pan endocrine therapy resistance is almost inevitable. While many mechanisms for intrinsic and acquired endocrine resistance have been explored, links between defects in DNA repair, the fundamental drivers of cancer pathogenesis, and endocrine therapy resistance have been understudied. Here we link mismatch repair (MMR) deficiency to poor clinical outcomes in ER+ breast cancer using whole exome DNA sequencing data and mRNA expression analysis. We subsequently demonstrate that MMR deficiency bypasses ER dependent cell cycle regulation through disruption of Chk2/p21-mediated feedback inhibition of CDK4 in breast cancer cell lines and tumor samples, as well as through correlations with human clinical data. We also show that pharmacological targeting of CDK4 significantly inhibits growth of MMR-deficient ER+ breast cancer cells in vitro and in vivo. This mechanism provides a new explanation for why endocrine therapy resistant ER+ breast cancers can respond to CDK inhibition and suggests that primary tumors exhibiting MMR deficiency are good candidates for adjuvant CDK4 inhibitor treatment. Citation Format: Haricharan S, Schmelz J, Schmidt C, Singh P, Holloway K, Anurag M, Suman V, Olson JA, Hunt K, Bainbridge MN, Ellis MJ. Mismatch repair deficiency induces endocrine therapy resistance in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD2-06.

91 Background: Formal mechanisms to share data on quality remain immature in specialty palliative care. As the field grows, infrastructure that promotes collaboration among academic and community-based practice will be required to foster comparisons and benchmarking of data to inform areas for quality improvement. Further, such relationships will create a palliative care “quality improvement laboratory”, where proposed guidelines and best practices can be developed, implemented, and tested. Methods: We set out to bring together specialty palliative care practices with a shared vision for collaborative quality improvement. We modeled our approach after the Institute for Healthcare Improvement Breakthrough Series alongside our Rapid Learning Quality Improvement paradigm. We use a set of common data collection procedures, across an electronic point-of-care platform called Quality Data Collection Tool (QDACT), alongside a centralized data registry. Further, we meet and discuss challenges and issues, compare best practices, and brainstorm new projects through biweekly conference calls. Results: We have created a multi-institutional collaboration for quality assessment and improvement in specialty palliative care. Termed the Global Palliative Care Quality Alliance, we have brought together 11 academic and community organizations, both general and oncology-specific, across six states to study various areas of quality practice. Short-term, we will conduct rapid-cycling quality improvement projects addressing National Quality Forum domains for quality palliative care, including documentation of spiritual assessment and timely advance care planning. Long-term, we aim to study the link between quality measure adherence and outcomes and further align our initiatives with those of other large consortia, like the Palliative Care Research Cooperative and Palliative Care Quality Network. Conclusions: Collaborative quality improvement is needed in specialty palliative care across a national platform. Developing the infrastructure to perform standardized quality improvement is achievable across multiple palliative care settings.