Cassivi, Stephen D.

239 Background: After trastuzumab (T) approval for advanced HER2-positive E/GEJ-AC, HER2 testing has increased in patients (pts) with resectable disease. Neoadjuvant carboplatin/paclitaxel chemoradiation (nCP-CRT) is a common therapy approach. We performed the largest evaluation, to our knowledge, of the prognostic impact of HER2 in E/GEJ-AC pts treated with nCP-CRT. Methods: We retrospectively reviewed medical records of all trimodality-eligible (T2+ or N+) pts with E/GEJ-AC who started nCP-CRT (usually 50.4 Gy) with planned surgery at Mayo Clinic (2014-2019). HER2 was tested using standard criteria for HER2 positivity (ie, immunohistochemistry 3+ or amplification by in situ hybridization). Clinicopathologic data and time to recurrence (TTR), disease free survival (DFS), overall survival (OS), survival after recurrence (SAR), and pathologic complete response (pCR – ie, no residual tumor in primary or nodes) were collected. Kaplan Meier and multivariate Cox analysis were used. Results: Of 161 consecutive eligible pts, HER2 status was available in 107 pts (HER2-positive n=26, HER2-negative n=81) of whom n=82 had surgery and n=19 had pCR. Most tumors were clinical T3 (80%) or N+ (81%), histologic grade 3 of 3 (62%). HER2 positivity was significantly associated with lower grade, but not with age, clinical T or N, or ECOG performance status (PS). A similar proportion of HER2-positive ( vs negative) pts had surgery. Among pts who had surgery, pCR rates were lower in HER2-positive ( vs negative) pts (11% [2/19] vs 27% [17/63]). After a median follow up of 23 mo, DFS and TTR were significantly shorter in HER2 positive ( vs negative) pts, independent of other pretreatment covariables (Table). Yet OS was comparable. Lung recurrence was enriched in HER2 positive ( vs negative) pts. Among pts with recurrence, SAR was longer in HER2-positive vs -negative pts. A total of 53% (10/19) of previously HER2-positive pts received T-based therapy after recurrence, and these pts were the drivers of favorable SAR (median 22 mo in n=10 HER2-positive pts who received T vs 11 mo in n=9 HER2-positive pts who did not receive T vs 11 mo in n=40 HER2-negative pts; P log-rank=.01). Conclusions: HER2 positivity ( vs negativity) is independently associated with shorter TTR and DFS, but more comparable OS. The adverse association of HER2 on tumor response and TTR may have been largely overcome through enhanced survival after recurrence, although OS data are maturing. These data may have implications for the design of endpoints in future curative-intent anti-HER2 trials. [Table: see text]

Importance: A postoperative video telemedicine follow-up program was introduced by the Mayo Clinic. An attempt was made to understand the potential cost savings to patients before contemplating full-scale expansion across all potentially eligible surgical patients and practices. Objective: The primary purpose was to estimate potential cost savings to patients with video telemedicine follow-up to home compared with face-to-face follow-up in a standard clinic setting. Design: The research was designed collaboratively by the Center for Connected Care and the surgical practice to address the question of estimated cost savings of postoperative video telemedicine visits. The intervention arm is the postoperative video telemedicine follow-up visit to home setting and the comparator is the face-to-face visit at Mayo Clinic. Setting: Large, integrated, academic multispecialty practice supporting patient care delivery, research, and education. Participants: The population under study comprised routine uncomplicated postoperative patients who underwent video telemedicine or face-to-face follow-up visits that fell within the 90-day global period across multiple (general, neurosurgery, plastic, thoracic, transplant, and urology) surgical specialties. Main Outcome(s) and Measure(s): Economic outcomes were cost of travel, accommodations, meals, and missed work. Additional outcomes included time expenditure and patient satisfaction. Cost/benefit analysis unit was US dollars (USD). All costs were inflated to 2018 USD, using the Gross Domestic Product Implicit price deflator. Results: Patients who utilized video telemedicine rather than face-to-face clinic visit for postoperative follow-up were estimated to save $888 per visit on average. More specifically, patients residing more than 1,635 miles round trip from clinic saved an estimated $1,501 per visit and patients not needing accommodation still saved an estimated $256 per visit. Patient satisfaction over video telemedicine postoperative follow-up visits remained high over the 6-year period of study. Conclusions and Relevance: The use of video telemedicine for routine uncomplicated postoperative follow-up visits to replace face-to-face follow-up visits has the potential to be financially advantageous for patients. Key points Question: For postoperative patients, what are the health economic outcomes associated with video telemedicine follow-up to home compared with face-to-face follow-up in a standard clinic setting? Findings: Video telemedicine offers a cost benefit for patients through avoidance of travel costs and missed work. Meaning: For uncomplicated routine postoperative follow-up visits, video telemedicine is a less costly alternative for most patients.

e19013 Background: Mutation profiling to assess for potentially druggable mutations in NSCLC is being offered at an increasing number of cancer centers throughout North America and internationally. Although data continue to accumulate for the potential value of mutation testing in designing chemotherapeutic regimens, the treatment impact of obtaining information beyond assessment of EGFR and ALK status remains unclear. How best to obtain and clinically utilize these data, including information from exome and whole genome sequencing, also remains unclear. Methods: Patients were reviewed electronically in a multidisciplinary conference regarding indications for testing and results of mutation profiling from various methods, including the mass-spec based LungCarta test, targeted NexGen sequencing, exome, and whole genome sequencing. Outcomes of the multidisciplinary review were communicated back to treating physicians. Results: Mutation testing was performed on 200 patients using a variety of approaches. The majority (>150) were surgically resected stage I and II tumors. Mutations in at least 1 major cancer driver gene, including EGFR, KRAS, MET, BRAF and PIK3CA, were found in 47% of all patients tested. EGFR mutations were present in 14.8% of patients tested, KRAS 21.3%, BRAF 2.6%, PIK3CA 3.2%, and MET 4.5%. A total of 8 patients underwent either exome or whole genome sequencing. A limited number of patients (<10) had mutation results that impacted treatment decisions from this cohort. Conclusions: Mutation profiling can influence treatment decisions in NSCLC, but at a low frequency. The role of exome and or whole genome sequencing for patients with NSCLC is evolving and remains undefined.

4062 Background: Multiple clinical trials have incorporated preoperative chemotherapy and radiation (RT) in an attempt to improve local tumor control, distant disease failure and overall survival rates for locally advanced but resectable adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ). This multicenter, cooperative group study combined active chemotherapy agents cisplatin (C), docetaxel (D) and the targeted EGFR agent panitumumab (P) in the induction phase followed by concurrent chemotherapy (CDP) and radiation. Pathologic complete response (pCR), a surrogate for improved survival, was the primary endpoint. Methods: From 01/15/09 to 07/22/11, 70 patients (pts) with Siewert I or II adenocarcinomas and clinical stages T3N0M0, T2-3N1M0 or T2-3N0-1M1a (celiac LN ≤ 2 cm) were accrued. Patients received cisplatin (40 mg/m2), docetaxel (40 mg/m2) and panitumumab (6 mg/kg) on weeks 1, 3, 5, 7, 9 with RT (5040 cGy, 180 cGy/day x 28d) beginning week 5. The decision rule had a 90% power with a 0.10 significance level to detect a pCR rate of at least 35%. Secondary objectives included near-pathologic complete response (near-pCR), toxicity, and overall and disease-free survival rates. Results: Five pts were ineligible. Of the remaining 65 pts (59 M, 6 F; median age 61), 12 pts did not undergo surgery (5 progressed, 4 refused, 3 other). Of the 58 evaluable pts, the pCR rate was 32.8% (90% CI: 22.6% -42.9%) and near-pCR 22.4% (90% CI: 13.4%-31.4%). Total doses of C, D, and P were achieved in 76%, 80%, and 73%, respectively (n = 70). 66 pts (94%) received the total RT dose. Sixteen pts (23%) had a grade 4+ non-heme adverse event possibly related to treatment. Venous thrombosis (5 pts) was most common. Conclusions: The CDP regimen in the neoadjuvant setting in patients with esophageal adenocarcinomas is active (pCR + near-pCR = 55.2%) and feasible. The toxicity though tolerable is substantial.

Abstract OBJECTIVES Paragangliomas have unique features in the mediastinum, in part due to their location. Because of their paucity, they have not been thoroughly investigated. We studied the clinical, pathological, immunohistochemical and molecular features of mediastinal paragangliomas. METHODS Immunohistochemistry, next-generation sequencing mutation panel and the Oncoscan assay were performed. RESULTS Twenty-four patients with mediastinal paraganglioma (7 men, 29.2%) had a median age of 45.5 years (19.8–72.2). Twenty-one (87.5%) paragangliomas were completely resected. Six (of 24, 25.0%) tumours were considered metastatic. Mitotic activity occurred in 11 (of 24, 45.8%) paragangliomas. Programmed death-ligand 1 (PD-L1) (n = 23) was expressed in 6 (26%) patients in 10% (n = 2) and 1% (n = 4) of tumour cells, respectively. SDHB expression was lost in 19 (of 22, 86.4%) cases. ATRX expression was lost in 11 (of 23, 47.8%) cases. Next-generation sequencing revealed a single pathogenic mutation in 10 (of 19) specimens including SDHB (n = 4), SDHD (n = 6), SDHC (n = 1), ATRX (n = 1), and ≥2 mutations in 2 cases [SDHC and TERT (n = 1); SDHB, ATRX and TP53 (n = 1)]. Germline mutation analysis revealed the same succinate dehydrogenase mutation (or lack thereof) as identified in the paraganglioma in 11 (of 12) cases. During a median follow-up (n = 21) of 4.8 years (0.8–14.9), 3 patients developed metastases; 4 patients died, at least 1 of disease. CONCLUSIONS Mediastinal paragangliomas can be associated with morbidity and mortality. Many mediastinal paragangliomas have been reported to be associated with syndromes such as multiple endocrine neoplasia, von Hippel-Lindau or succinate dehydrogenase syndrome with mutation profiles dominated by alterations in genes associated with these syndromes.

Abstract OBJECTIVES The aim of this study is to evaluate the efficacy of chest computed tomography (CT) to predict the pathological stage of thymic epithelial tumours (TET) using the recently introduced tumour, node and metastasis (TNM) staging with comparison to the modified Masaoka staging. METHODS Preoperative chest CT examinations in cases of resected TET with sampled lymph nodes (2006–2016) were retrospectively reviewed by 2 thoracic radiologists and radiologically (r) staged using both staging systems. A thoracic pathologist reviewed all cases for the pathological (p) stage. Concordance between r-staging and p-staging was assessed by % agreement and unweighted kappa statistics. Associations between r-stage and p-stage with outcomes were assessed using the Cox proportional hazards regression. RESULTS Sixty patients with TET were included (47 thymomas, 12 thymic carcinomas and 1 atypical carcinoid tumour). Sixteen patients (26.7%) had received neoadjuvant therapy. Fifty-four patients (90.0%) had complete resection. The overall agreement between the r-stage and p-stage was 66.7% (κ = 0.46) for TNM staging and 46.7% (κ = 0.30) for modified Masaoka staging. Agreement between r-assessment and p-assessment of the T, N and M components of the TNM stage was 61.7% (κ = 0.28), 86.7% (κ = 0.48) and 98.3% (κ = 0.88), respectively. CT overstaged 12 patients (20.0%) for TNM staging and 12 patients (20.0%) for modified Masaoka staging and understaged 8 (13.3%) and 20 (33.3%) patients for TNM staging modified Masaoka staging, respectively. The r-TNM staging accuracy was lower for patients with neoadjuvant therapy (50.0% with vs 72.7% without). During a median follow-up of 2.6 years (range 0.1–10.5 years), 12 patients had metastases and/or recurrence; 11 patients died (4 of disease). The r-TNM stage and modified Masaoka stage were associated with overall survival and progression-free survival (P < 0.001). CONCLUSIONS Preoperative chest CT is able to accurately predict p-TNM stage in two-thirds of surgically resected TET, with an agreement between radiological staging and pathological staging superior to the modified Masaoka staging.

Abstract Background Pneumatosis intestinalis has long been a marker of advanced bowel ischemia and prompts urgent laparotomy. In post-operative settings, the presence of pneumatosis represents a significant management dilemma. We share a case-series of post-esophagectomy patients with pneumatosis intestinalis and no corollary intra-abdominal pathologic findings on re-exploration. Methods January 2000 to December 2017, 1760 patients underwent Ivor-Lewis esophagectomy or gastrectomy with jejunostomy-tube placement. Charts were reviewed retrospectively to identify patients with pneumatosis intestinalis discovered in the post-operative period. Demographic data, operative details and postoperative course were reviewed including incidence and details of re-exploration. Results Eleven patients met inclusion criteria. Nine were male (81.8%) and mean age was 69 years. All patients had radiographic confirmation of pneumatosis intestinalis and in many cases portal venous gas (Figure 1). Clinical course was variable without discernable trends in vitals or laboratory values. Development of significant postoperative ileus along with delivery of enteral tube feeds through a jejunostomy tube preceded development of the pneumatosis in all patients. Nine patients were re-explored and none had evidence of bowel ischemia. Conclusion The finding of pneumatosis intestinalis in the post-operative setting can be alarming and pose a management dilemma. With the advent of improved and readily available imaging, there has been an increase in findings that have no corollary physical symptomatology. In this series of patients, despite dramatic radiographic findings, none had ischemic bowel. Pneumatosis intestinalis alone in patients who have undergone esophagectomy should not be considered an indication for emergency re-exploration. Disclosure All authors have declared no conflicts of interest.

Abstract Background The purpose of this study was to evaluate the survival difference in clinical T2N0 esophageal cancer patients receiving neoadjuvant chemoradiotherapy (CRT) vs. upfront surgery. Methods Between 1/1/1995 to 12/31/2012, a prospectively maintained database was used to identify patients with cT2N0 esophageal adeno- and squamous cell carcinoma. Exclusion criteria included: lack of endoscopic esophageal ultrasonographic (EUS) staging, incomplete resection, and prior treatment with endoscopic mucosal or submucosal resection. Cox-proportional hazard ratios were used to compare the primary outcomes of overall (OS) and disease-free survival (DFS). Secondary outcomes included: rate of postoperative complications, rate of pathologic upstaging/response, and induction/adjuvant treatment completion rate. Pre-hoc subgroup analysis compared pathologically upstaged patients receiving upfront surgery followed by adjuvant chemotherapy to those treated with neoadjuvant CRT. Results A total of 161 cT2N0 esophageal cancer patients were identified based on EUS staging. Upfront surgery was offered to 134 patients (83%), with 27 patients (17%) receiving induction CRT. Univariate analysis did not demonstrate any significant baseline differences between the two groups. In the upfront surgery group, 53 (39.6%), 28 (20.9%) and 53 (39.6%) patients were pathologically down-staged, accurately staged and upstaged respectively. Upstaging was higher in the upfront surgery group (53/134, 39.6% vs. 4/27, 14.8%; P = 0.02), while 11/27 (40.7%) patients receiving neoadjuvant CRT demonstrated complete pathologic response. Of those eligible for adjuvant chemotherapy, only 21/55 (38.2%) received treatment. In the neoadjuvant CRT group, 51.9% completed all planned therapy, compared to 23.6% of patients treated with upfront surgery followed by adjuvant chemotherapy (P = 0.01). Cox proportional hazard ratio did not demonstrate an advantage to induction CRT in terms of OS (HR = 1.64, P = 0.43) or DFS (HR = 1.36, P = 0.69). In general, patients with pathologic upstaging had worse OS (HR = 2.73, P = 0.001) and DFS (HR = 4.18, P = 0.003). Conclusion EUS was only accurate in staging T2N0 patients in 20.9% of cases. While neoadjuvant CRT did not confer a survival advantage, these results likely reflect the low number of patients being referred for induction therapy. Neoadjuvant CRT was however associated with lower rates of pathologic upstaging and higher rates of treatment completion. Further research should evaluate the survival outcomes in pathologically upstaged cT2N0 patients not receiving neoadjuvant therapy. Disclosure All authors have declared no conflicts of interest.