Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3-42 in.; resolution, 1280 × 800-3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm 2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.

CRA501 Background: Olaparib (AZD2281; KU-0059436) is a novel, orally active PARP inhibitor that induces synthetic lethality in homozygous BRCA-deficient cells. A phase I trial identified 400 mg bd as the maximum tolerated dose (MTD) with an initial signal of efficacy in BRCA-deficient ovarian cancers (ASCO 2008; abst 5510). The primary aim of this study was to test the efficacy of olaparib in confirmed BRCA1/BRCA2 carriers with advanced refractory breast cancer. The secondary aim was to assess safety and tolerability in this population. Methods: In an international, multicenter, proof-of-concept, single-arm, phase II study, two sequential patient (pt) cohorts received continuous oral olaparib in 28-day cycles initially at the MTD, 400 mg bd (27 pts), and subsequently at 100 mg bd, a previously identified PARP inhibitory dose (27 pts). Eligibility criteria included confirmed BRCA1/BRCA2 mutation and recurrent, measurable chemotherapy-refractory breast cancer. The primary efficacy endpoint was best objective response rate (ORR; RECIST) post baseline. Progression-free survival (PFS) and clinical benefit rate were secondary endpoints. All adverse events were reported using CTCAE v3. Results: On November 20, 2008, 54 pts exposed to a median of three prior lines of chemotherapy had been enrolled. 27 pts were dosed at 400 mg bd (18 BRCA1 deficient and 9 BRCA2 deficient), and 24 of these had databased RECIST assessments. The ORR (currently based on unconfirmed responses) was 38% (9/24) (400 mg bd). Causally-related toxicity was mainly mild (grade 1–2) in severity; 9/27 pts (33%) had fatigue; 7/27 (26%) had nausea; 4/27 (15%) had vomiting; and 1/27 (4%) had anemia. Causally-related grade 3 or higher toxicities were seen in 5 pts (19%) with fatigue (3 pts), nausea (2 pts), and anemia (1 pt). 27 pts were treated in the subsequent 100 mg bd cohort where no data are currently available. Conclusions: Olaparib at 400 mg bd is well tolerated and highly active in advanced chemotherapy-refractory BRCA-deficient breast cancer. Toxicity in BRCA1/BRCA2 carriers was similar to that reported previously in non-carriers. This first study with olaparib in BRCA-deficient breast cancers provides positive proof of concept for high activity and tolerability of a genetically defined targeted therapy. [Table: see text]