Search

395 Background: Understanding contemporary radiation therapy outcomes for prostate cancer (i.e., metastasis, death) is important for shared decision-making and setting expectations for patients and providers. Unfortunately, long-term outcome estimates are often derived from meta-analyses of outdated prospective clinical trials or population-based data lacking reliable clinical details (e.g., incident metastatic disease). For these reasons, we used a recently validated, natural language processing algorithm to identify incident metastatic prostate cancer within the electronic medical records of men treated with radiation therapy for localized prostate cancer in order to conduct an innovative and contemporary population-based survival outcomes study. Methods: We used national administrative, cancer registry, and electronic health record data for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy (ADT) within the Veterans Health Administration from 2005 to 2015. We used National Death Index data through 2019 for overall and prostate cancer-specific survival, and identified the date of incident metastatic prostate cancer using a validated natural language processing algorithm. We estimated metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods. Results: We identified 41,876 patients treated with definitive radiation therapy for prostate cancer from 2005 through 2015, and followed them for over 8 years (follow up, median, 8.7 years, age at diagnosis, median, 65 years). Most patients had intermediate (42%) and high risk (33%) disease, with nearly half treated with ADT as part of initial therapy (44%). Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low, intermediate, and high risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low, intermediate, and high risk disease. Unadjusted overall survival was lower across disease risk categories at 77%, 71%, and 62% for low, intermediate, and high risk disease. Conclusions: These data provide population-based benchmarks for clinically relevant endpoints, including metastasis-free survival, among patients with low, intermediate, and high risk prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high risk disease, in particular, compare favorably with historical outcomes.

5090 Background: Accurate survival estimates after prostatectomy are critical for patient counseling, treatment decisions, and trial design. Prior prostate cancer natural history studies may not reflect contemporary outcomes and often lack key endpoints (e.g. incident metastases). For these reasons, we explored population-based recurrence and survival following radical prostatectomy. Methods: We conducted a retrospective study of men with localized prostate cancer treated with radical prostatectomy from 2005-2015 with follow up through 2019 in the Veterans Health Administration. We excluded men with adjuvant radiation or hormonal therapy and defined biochemical recurrence (BCR) as a PSA ≥0.2 ng/mL. We used a validated natural language processing encoded dataset to identify incident metastatic disease. We then estimated actuarial time from surgery to BCR, BCR to metastatic disease, and metastatic disease to death using Kaplan-Meier methods. Results: Of 22,033 men post-prostatectomy, 5,963 (27%) developed BCR, with 5- and 10-year BCR estimates of 21% and 29% (Table). Of 5,963 men with BCR, 678 (11%) developed metastasis, with 5- and 10-year metastasis-free survival from time of BCR of 91% and 77%. Of these 678 men with metastases, 235 died (35%), with 5- and 10-year overall survival of 61% and 47%. Median actuarial overall survival from incident metastatic disease was 8.8 years. Conclusions: On average, we found a man undergoing radical prostatectomy for localized prostate cancer can expect about a 1 in 4 chance of biochemical recurrence. Of men with BCR, we identified a 1 in 10 chance of developing metastases, surviving nearly 9 years after incident metastasis. Both metastasis-free survival after biochemical recurrence and overall survival after developing metastasis appear to have lengthened consistent with a long natural history after prostate cancer surgery. Novel advanced prostate cancer treatments may help explain these findings, though their optimal use warrants further study especially as advanced imaging techniques to characterize recurrence increase. [Table: see text]

3032 Background: Earlier detection of cancer could lead to improved outcomes. Non-invasive biomarkers are integral for early detection, and protein and DNA-based assays have been previously described for this purpose. Evaluation of highly expressed circulating RNA would improve upon existing methods by allowing for quantitation, however RNA expression in plasma is low. Circular RNA (circRNA) is formed by alternative backsplicing and provide resistance to exoribonclease-mediated degradation. Therefore, circRNA is more stable in plasma and could potentially be more easily detected non-invasively. Here, we report results from a novel assay that identifies and quantitates expression of circRNA in cancer plasma. Methods: Cancer-specific circRNA targets were identified by analyzing differential expression and abundance based on capture RNA sequencing in tissues. CircRNA-specific probes were designed and validated by stable expression with RNAse R incubation. Expression of selected circRNA isoforms were measured using a quantitative PCR-based assay. For breast cancer specimens, plasma was collected from a cohort of 36 patients and 12 normal female controls without known cancer diagnosis. Expression was determined by normalizing signal to two averaged universally expressed circRNAs. Differential expression for each target was determined for cancer vs. normal and stratified based on ER and HER2 positivity as well as stage. Results: Normalized expression of seven proposed breast cancer-specific circRNA targets was determined for all patients in the cohort. All targets demonstrated resistance to RNAse R-mediated degradation in breast cancer cell lines. In the breast cancer cohort, CircTRPS1 expression was higher in cancer plasma than normal, trending toward significance. Expression of circTRPS1 was significantly more common in ER-negative than ER-positive breast cancer (p = 0.02). CircPDHX expression was elevated in normal plasma compared to cancer and relatively higher in ER-positive than ER-negative cancer (p = 0.05). Median expression in plasma was elevated in cancer specimens compared to normal for CircVAV3, circDNAH14, and circCDYL. CircERBB2 expression was also relatively higher in HER2-positive cancer when compared to other targets. Higher expression significantly positively correlated with metastatic disease for circERBB2 (p = 0.01) and circCDYL (p = 0.005) and negatively correlated with metastasis for circWDR78 (p = 0.02). Conclusions: CircRNA are promising biomarkers for early non-invasive detection of cancer. We identified seven circRNA biomarkers in breast cancer plasma which correlated with clinical characteristics. Three circRNAs were significantly prognostic for metastatic breast cancer. Identification of additional cancer-specific targets and multiplexing markers is underway. This assay is generalizable to other cancers, and similar studies in prostate and bladder cancer are in progress.

Purpose We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964. Patients and Methods We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD. Results Diffuse large B-cell lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's lymphoma (n = 7), Burkitts lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred sooner after SOT than EBV-negative tumors (mean, 29 v 66 months). Extralymphatic disease (79%), poor performance status (68%), elevated lactate dehydrogenase (LDH; 71%), and advanced stage (68%) disease were all common at the time of lymphoma diagnosis. Two thirds of patients had a complete response when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone–like chemotherapy (either with or without rituximab). Median overall survival in all patients with PTLD was 8.23 years (95% CI, 2.28 to 30.0 years). Conclusion EBV-naïve patients who receive a donor organ from an EBV-infected donor are in the highest-risk situation for PTLD development. Most of these lymphomas are CD20 positive. Follicular lymphoma is unusual. With treatment, survival of patients with PTLD was indistinguishable from that of the SEER population sample.

Purpose Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. Patients and Methods This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. Results Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). Conclusion These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.

Purpose: To evaluate the role of breast tumor location on survival in patients with breast cancer. Patients and Methods: We evaluated tumor location within the breast on breast cancer–specific survival (BCSS) and overall survival (OS) in patients with invasive breast cancer using the Surveillance, Epidemiology, and End-Results (SEER) registries in the United States. Effects on survival were evaluated according to age, stage, tumor site, tumor size, grade, axillary lymph node status, extent of surgery, and radiotherapy (RT). A multivariate model was used with complete data on 45,880 patients. The median follow-up was 59 months. Results: Patients with outer tumor location demonstrated superior BCSS on Kaplan-Meier analysis for both local stage (node-negative, P < .001) and regional stage disease (node-positive, P = .0002). For BCSS, the hazard ratio (HR) for inner quadrant location compared with outer quadrant was 1.31 (95% confidence interval [CI], 1.19 to 1.37; P < .001); and for OS, the HR was 1.12 (95% CI, 1.05 to 1.17; P < .001). When ER and PR status were included in the model, the HR for inner quadrant location compared with outer quadrant was 1.27 for BCSS (95% CI, 1.16 to 1.40; P < .001) and 1.11 for OS (95% CI, 1.03 to 1.19; P = .004). Patients treated by lumpectomy that received RT had a superior OS compared with patients that did not receive RT in both local (HR, 0.52; 95% CI, 0.48 to 0.61; P < .001) and regional (HR, 0.63; 95% CI, 0.56 to 0.72; P < .001) stage disease. Mastectomy patients with local stage disease that received RT had a diminished OS (HR, 1.24; 95% CI, 1.02 to 1.50; P = .033). Conclusion: On multivariate analysis, incorporating data on age, stage, tumor site, tumor size, grade, ER and PR status, axillary lymph node status, extent of surgery, and RT, this SEER registry–based study demonstrates that medial tumor location adversely impacts BCSS and OS.