MLH1-methylated endometrial cancer under 60 years of age as the "sentinel" cancer in female carriers of high-risk constitutional MLH1 epimutation.

OBJECTIVE: Universal screening of endometrial carcinoma (EC) for mismatch repair deficiency (MMRd) and Lynch syndrome uses presence of MLH1 methylation to omit common sporadic cases from follow-up germline testing. However, this overlooks rare cases with high-risk constitutional MLH1 methylation (epimutation), a poorly-recognized mechanism that predisposes to Lynch-type cancers with MLH1 methylation. We aimed to determine the role and frequency of constitutional MLH1 methylation among EC cases with MMRd, MLH1-methylated tumors. METHODS: We screened blood for constitutional MLH1 methylation using pyrosequencing and real-time methylation-specific PCR in patients with MMRd, MLH1-methylated EC ascertained from (i) cancer clinics (n = 4, <60 years), and (ii) two population-based cohorts; "Columbus-area" (n = 68, all ages) and "Ohio Colorectal Cancer Prevention Initiative (OCCPI)" (n = 24, <60 years). RESULTS: Constitutional MLH1 methylation was identified in three out of four patients diagnosed between 36 and 59 years from cancer clinics. Two had mono-/hemiallelic epimutation (∼50% alleles methylated). One with multiple primaries had low-level mosaicism in normal tissues and somatic "second-hits" affecting the unmethylated allele in all tumors, demonstrating causation. In the population-based cohorts, all 68 cases from the Columbus-area cohort were negative and low-level mosaic constitutional MLH1 methylation was identified in one patient aged 36 years out of 24 from the OCCPI cohort, representing one of six (∼17%) patients <50 years and one of 45 patients (∼2%) <60 years in the combined cohorts. EC was the first/dual-first cancer in three patients with underlying constitutional MLH1 methylation. CONCLUSIONS: A correct diagnosis at first presentation of cancer is important as it will significantly alter clinical management. Screening for constitutional MLH1 methylation is warranted in patients with early-onset EC or synchronous/metachronous tumors (any age) displaying MLH1 methylation.

Developing a survivorship care plan (SCP) delivery process for patients and primary care providers serving poor, rural, and minority patients with cancer.

BACKGROUND: Survivorship care plans (SCPs) summarize patients' treatment and act as an education and communication tool between oncologists and primary care providers (PCPs). But creation and delivery of SCPs are challenging, labor intensive, and costly. The University of New Mexico Comprehensive Cancer Center (UNM CCC) treats a poor, rural, and minority patient population, and our purpose was to implement and evaluate a process to create and deliver SCPs to patients and PCPs. METHODS: Providers placed an electronic SCP order, basic information was imported, and staff compiled treatment details. Flagged SCPs were then ready for delivery, providers approved of and delivered the SCP at the next encounter, and the SCP was sent to the PCP. RESULTS: By April 2020, 283 SCPs were ordered, 241 (85.2%) were created by the designated staff, and 97 (34.2%) were given to patients after definitive therapy for breast cancer (59.1%), gynecological cancers (10.8%), prostate cancer (7.4%), colorectal cancer (5.1%), and lymphomas (4.8%). Of 97 SCPs eligible to be sent to PCPs, 75 (77.3%) were mailed or sent via EMR. Of the 41 (48.9%) SCPs sent via mail or fax, only 8 (8.3%) were received and 5 (5.2%) integrated. CONCLUSIONS: This study shows that SCPs can be delivered to patients in a poor, rural, and minority patient population but that PCP receipt and integration of SCPs are poor. Future efforts need to ensure that an oncologist to PCP education and communication tool is able reach and be integrated by PCPs.