e23281 Background: SCCBis a rare, aggressive form of breast cancer that is associated with extremely poor outcomes (Hare 2015). In an effort to identify new treatment options, we utilized comprehensive genomic profiling to assess the potential for novel therapies in SCCB. Methods: Under an IRB approved protocol, we identified patients (pts) with SCCB and SCLC profiled by Caris Life Sciences between 2007-2015. Tumors were assessed with up to 21 IHC stains, in situ hybridization (ISH) of cMET, EGFR, HER2 and TOP2A, and next generation sequencing (NGS) as well as Sanger sequencing of 47 genes. Results: 19 patients with SCCB were identified, median age was 58 years (range 37-79) and 42% had metastatic disease at presentation; for comparison 58 pts with SCLC were identified (66 [36-86], 65% metastatic). By IHC 30% SCCB pts expressed ER, 15% expressed PR and 18% expressed androgen receptor; SCLC pts expressed ER 0%, PR 2%, AR 6%. SCCB and SCLC pts had similar patterns of other IHC expression (0% v 0% PDL1, 50% v 42% PD1, 80% v 95% TOP2A, respectively). All SCCB and SCLC pts were negative for HER2 and cMET amplification by ISH. NGS revealed TP53 mutations in 75% of patients both with SCCB and SCLC and PIK3CA mutations in 38% of SCCB pts but no SCLC pts (Fisher’s exact test p = 0.005, OR 0.02 [0.00-0.52]). No other mutations were found in SCCB pts and no other mutation occurred in over 10% of SCLC pts except RB1 in 20% (p = 0.31). Conclusions: SCCB is an aggressive tumor with few therapeutic options. Molecular profiling suggests many similarities between SCCB and SCLC with the exception an increased incidence of PIK3CA mutations in SCCB, which may have therapeutic implications.
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.
e18079 Background: Treatment of head and neck squamous cell carcinoma (HNSCC) with multimodality therapy has improved locoregional control and overall survival. No benefit has been shown in patients over age 70. We evaluated patterns of care in older (≥65) vs. younger patients receiving curative-intent therapy. Methods: An institutional database was queried for patients diagnosed with HNSCC between January 2012 and May 2017, for whom curative-intent therapy was planned. Patients were stratified into a younger cohort (age 18-64 years) and an older cohort (≥ 65 years). Radiation treatment intent, use of chemotherapy, and completion of planned treatments were evaluated. Descriptive statistics were incorporated with Chi-squared or Fisher’s exact test. Logistic regression was used to estimate associations between age, stage, and chemotherapy received. Results: A total of 409 patients were identified, with 130 older patients. There was no difference in adjuvant vs. definitive treatment intent by age group (P = 0.54). Younger age was associated with higher likelihood of completing planned radiation dose (63.6% vs.28%, P = 0.04). There was no difference in variability of number of radiation days between the older and younger cohorts (49.6 ± 36.1 days, vs. 51.3 ± 13 days). Patients in the older subset were more likely to be treated with radiation alone (48.5% vs. 24.7%, P < 0.001), and less likely to be treated with a platinum-based regimen (47% vs. 69%, P < 0.001). Adjusted for T- and N-stage, there was a statistical trend between age and chemotherapy agent (P = 0.093); compared to receiving no chemotherapy, younger patients were 1.9 times more likely to receive a cisplatin-containing regimen compared to older patients (95% CI, 1.06-3.44). Conclusions: Older patients with HNSCC treated with curative therapy are less likely to receive chemotherapy, and less likely to receive platinum agents, compared to younger patients. Further study is needed to define populations of older adults who may better tolerate combined modality therapy.
Background: While the provider volume-outcome relationship has been established for many complex surgeries and invasive procedures, the provider volume impact on outcomes for Hodgkin lymphoma (HL) is less certain. We hypothesized that high-volume providers (HVPs) may have superior outcomes compared with low-volume providers (LVPs). Methods: We performed a chart-based, retrospective review of all patients receiving adriamycin, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for HL at the West Cancer Center from January 2010 to June 2015. Patients were divided into HVP (> 3 inpatient chemotherapy (CT)/month (m)) versus LVP (< 3 CT per m) groups. Of 95 patients identified, 93 received at least one dose of ABVD, 21 treated by HVP and 72 by LVP. Patient characteristics were well balanced between groups. Results: HVPs were less likely to prescribe dose delays (odds ratio (OR): 0.32; confidence interval (CI): 0.16 - 0.65; P = 0.0007) and to hold doses for afebrile neutropenia (OR: 0.05; CI: 0.00 - 0.85; P = 0.0006). HVP delivered significantly fewer prophylactic growth factors (0% of doses vs. 42%, OR: 0.00; CI < 0.00 - 0.06; P < 0.0001). Both event-free survival (EFS) (HR: 6.68; CI: 1.10 - 7.63; P = 0.0321) and overall survival (OS) (HR: 3.68; CI: 1.11 - 12.22; P = 0.032) were significantly inferior in the patients treated by LVP. Conclusions: In this study, patients with HL treated by LVP had inferior outcomes compared with those treated by HVP. HVPs were less likely to prescribe dose delays, hold doses for afebrile neutropenia or administer growth factor prophylaxis. These observations need to be confirmed in alternative datasets. World J Oncol. 2018;9(2):46-49 doi: https://doi.org/10.14740/wjon1093w
