We evaluated surgical trends for gastric diffuse large B-cell lymphoma (gDLBCL) before and after the approval of rituximab and whether an association of early mortality existed in patients treated after approval of rituximab.We utilized the Surveillance Epidemiology and End Results (SEER) 18 database to extract data on patients with gDLBCL diagnosed between 1983-2012. Primary site-specific cancer-directed surgery using SEER site-specific surgical codes and annual trends were analyzed. Patients were analyzed before and after 2006, the year rituximab gained U.S. Food and Drug Administration approval.Joinpoint trend analysis showed the sharpest decline in surgical rates between 2000-2010. Adjusted surgical rates computed using poisson regression declined from 54.4% in 1983 to 6.9% in 2012, with an annual percentage change of -8.9% (95% confidence interval=-9.7% to -8.3%; p-value <0.01). No significant mortality increase at 30 and 60 days was found.While rituximab appears to have significantly changed how surgery is utilized for patients with gDLBCL, early mortality was unchanged.
e17053 Background: As we have previously reported, SCCOis a rare, aggressive form of ovarian cancer associated with poor outcomes (Jamy 2015). In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. Methods: Under an IRB approved protocol, we identified patients (pts) with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O) and small cell carcinoma of the lung (SCLC) profiled by Caris (company info) between 2007-2015. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next generation sequencing (NGS) as well as Sanger sequencing of selected genes. Results: 46 pts with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 pts with SCLC. While small numbers prohibited comparisons SCCO patients were numerically younger (median 42 [range 12-75], SCCO-HT pts 26 [8-40] and NET-O pts 62 [13-76]) than SCLC pts 66 [36-86]. SCCO pts were numerically more likely to be metastatic (70%) than SCCO-HT (50%) or NET-O (33%) pts but at a similar rate to SCLC pts (65%). PD1 expression varied across tumor type with SCCO (100%), SCCO-HT (50%), NET-O (33%) vs SCLC (42%). PDL1 expression also varied with SCCO (50%), SCCO-HT (20%), NET-O (33%) and SCLC (0%). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 50% of SCCO pts having a BRCA2 mutation and 29% of pts with NET-O having PIK3CA mutations. No other actionable mutations were identified. Conclusions: SCCO/NET-O represent rare and difficult to treat malignancies. While randomized trials will be difficult these tumors may respond to biomarker guided checkpoint or PARP inhibitors.
Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases.Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant.Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453).Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings.Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1352.
Abstract Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases. Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant. Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453). Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings. Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1352.
As we have previously reported, small cell carcinoma of the ovary (SCCO) is a rare, aggressive form of ovarian cancer associated with poor outcomes. In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCO. Patients with SCCO, SCCO-HT (hypercalcemic type), neuroendocrine tumors of the ovary (NET-O), and small cell carcinoma of the lung (SCLC) profiled by Caris Life Sciences between 2007–2015 were identified. Tumors were assessed with up to 21 IHC stains, in situ hybridization of cMET, EGFR, HER2 and PIK3CA, and next-generation sequencing (NGS) as well as Sanger sequencing of selected genes. Forty-six patients with SCCO (10 SCCO, 18 SCCO-HT, 18 NET-O) were identified as well as 58 patients with SCLC for comparison. Patients with SCCO and SCCO-HT were younger (median 42 years [range 12–75] and 26 years [range 8–40], respectively) than patients with NET-O 62 [range 13–76] or SCLC 66 [range 36–86]. SCCO patients were more likely to be metastatic (70 %) than SCCO-HT (50 %) or NET-O (33 %) patients, but at a similar rate to SCLC patients (65 %). PD1 expression varied across tumor type with SCCO (100 %), SCCO-HT (60 %), NET-O (33 %) vs SCLC (42 %). PDL1 expression also varied with SCCO (50 %), SCCO-HT (20 %), NET-O (33 %) and SCLC (0 %). No amplifications were identified in cMET, EGFR, or HER2 and only 1 was found in PIK3CA (NET-O). Actionable mutations were rare with 1 patient with SCCO having a BRCA2 mutation and 1 patient with NET-O having a PIK3CA mutation. No other actionable mutations were identified. No recurrent actionable mutations or rearrangements were identified using this platform in SCCO. IHC patterns may help guide the use of chemotherapy in these rare tumors.
e20582 Background: There are no biomarkers that reliably predict benefit from PBC in NSCLC. We hypothesize cancers with DNA damage repair pathway nsSNPs may be more sensitive to PBC. Methods: Pts with advanced NSCLC that received first-line PBC and next-generation sequencing (NGS) with Caris (2013-2015) were retrospectively identified. The total pathogenic burden (SUM) was defined as test-determined pathogenic mutations (Pmut) plus nsSNPs predicted-damaging (pnsSNPs) by in silico analysis with PolyPhen-2 (Harvard). 13 DNA damage repair genes were also selectively analyzed. All p-values were two-tailed. Results: 84 pts were found; 35% female; 58% white, 37% black; median age was 64 (range 26-81); 82% had ≥20 pack-years (py), 12% with < 20 and 6% never-smokers; 27% received immunotherapy (IT) and 5% tyrosine kinase inhibitors (TKI) subsequently. 49 pts had primary progressive disease (58%), 9 stable disease (11%), 16 partial response (19%) and 10 complete response (12%). Median overall survival (OS) was 11 months (1-18). Median SUM was 5 (0-14) with median pnsSNPs 3 (0-11) and Pmut 1 (0-4). For all genes, no link was found between SUM and response (p = 0.95, ANOVA) or OS (p = 0.48, log-rank test). 26 pts (31%) had DNA damage repair lesions (range 1-3) with 33 nsSNPs (23/33 pnsSNPs) and 4 Pmut; genes commonly-mutated were ATM (16), BRCA2 (10) and BRCA1 (5). Race and smoking status did not predict mutation frequency. A trend towards better OS was seen for pts more heavily-mutated in DNA damage repair ( p= 0.01, log-rank test for trend) as > 60% pts with 1-3 nsSNPs survived > 300 days versus < 50% pts with 0. OS was longer for pts with 1+ DNA damage repair lesions (455 days) versus 0 (252 days) [HR 1.81; CI 1.19-3.89; p = 0.01]; no difference in response rate ( p= 0.59, Fisher’s exact) was found. Similar proportions of pts without (16/58; 28%) and with (7/26; 27%) DNA damage repair variants received IT; 4/4 pts TKI-treated had no such lesions. Conclusions: Advanced NSCLC tumors with ≥1 DNA damage repair nsSNP had a superior OS of > 200 days; however, no link with response was found. Further studies are indicated to determine the extent to which DNA damage repair burden can predict benefit in platinum-treated NSCLC pts.
4053 Background: PM from GC or GEJ portend a poor prognosis and molecular differences are ill defined. Methods: We compared genomic profiles of primary (P) GC and GEJ with PM patients (pts) and other metastases (OM) sent to Caris Life Sciences. Testing comprised immunohistochemistry (IHC) including programmed death ligand 1 (PD-L1) combined positive score (CPS), copy number alterations (CNA), 592-gene next-generation sequencing (NGS), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: 1366 cases were identified: 1041 GC (707 P, 98 PM, 236 OM) and 325 GEJ (248 P, 5 PM, 72 OM). PM were increased in GC versus GEJ (9% v. 2%, p < 0.0001). 91% GC and 93% GEJ were adenocarcinoma (AD); GC were more likely signet ring (SR) histology versus GEJ (11% v. 3%, p < 0.0001) and GC PM were more likely SR versus other OM or P (13% v. 12% v. 7%, p = 0.067). The mean age of PM pts (57 years) was younger than primary GC (63, p = 0.002) and OM (61; p = 0.044). More PM GC pts were female than P or OM (48% v. 35% v. 34%, p = 0.03). No molecular profiling differences were seen between GEJ and GC pts and they were combined for analysis; findings from 1246 AD pts are shown below (see Table). OM (9%, p = 0.041) had more CNA in CCNE1 than PM (2%, p = 0.041) or P (5%, p = 0.002). Conclusions: Compared to P and OM GC, PM pts were younger, more likely female and had a higher incidence of SR histology. PD-L1, HER2 IHC and ERBB2 CNA were reduced in PM versus P, suggesting novel therapeutic targets are needed. [Table: see text]
