Resected Pts Research Articles

Real-world treatment patterns and overall survival (OS) in locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC) in the U.S.

e23275 Background: Multimodal therapy, including definitive radiotherapy (RT) with or without systemic therapy (ST) or surgery followed by adjuvant RT ± ST is typically recommended for patients (pts) with LA HNSCC treated with curative intent. Assessing real-world use of various treatment modalities and OS helps to better understand the unmet needs in this population. Methods: The linked SEER-Medicare data (2007–2019) was used in this retrospective cohort study. Pts with newly diagnosed stage III-IVB (AJCC 6/7th) LA HNSCC (larynx, hypopharynx, oral cavity, or oropharynx) who received primary treatment within 4 months after initial diagnosis were included. HPV status was not available. OS from index date, i.e., primary treatment initiation date, was described using the Kaplan-Meier method. Baseline (12 months prior to index date) factors associated with OS were assessed using a Cox proportional hazards model. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were reported. Results: In total, 1885 pts met the selection criteria (median follow-up: 24.8 months). The mean age at initial diagnosis was 74.3 years, 67.2% were male, and 81.6% were white. Less than 1/3rd of pts received primary surgery (resected). More than half of resected pts received RT±ST post-surgery. In unresected pts, nearly 2/3rds received definitive concurrent RT+ST. The median OS and 5-year OS were 32.7 months and 37.6%, respectively, for all pts and were comparable between resected and unresected pts. In the multivariable Cox models for both resected and unresected pts, older age, more advanced tumor stage, hypopharynx (vs. oropharynx), and higher Charlson comorbidity index scores were associated with significantly shorter survival. Additionally, surgery followed by RT+ST (vs. surgery only) (HR = 0.50, 95% CI = 0.34-0.72, p < 0.001) and definitive RT+ST (vs. definitive RT only) (HR = 0.69, 95% CI = 0.58-0.81, p < 0.001) were associated with significantly longer survival in resected and unresected pts, respectively. Conclusions: In elderly pts with LA HNSCC, surgery followed by RT and definitive RT+ST were the most common treatment modalities in resected and unresected pts, respectively. The suboptimal real-world survival across all pts with LA HNSCC regardless of treatment strategy highlights a significant unmet need. Studies focused on the novel application and sequencing of effective immunotherapies are needed. Table 1. Primary treatment and OS in LA HNSCC1 [Table: see text]

Characteristics of patients (pts) with disease relapse despite absence of molecular residual disease (MRD) after resection of colorectal oligometastases (CRM): Implications from PRECISION study.

3602 Background: Detection of MRD after curative-intent resection of CRM is prognostic for disease relapse and may guide decisions regarding adjuvant chemotherapy (ACT). However, some pts without MRD detected immediately after resection may also experience disease relapse. We explored the features of pts enrolled in a prospective multicenter study with disease relapse who did and did not have post-resection MRD. Methods: Pts with previously untreated resectable CRM scheduled for surgery were prospectively enrolled between March 2021 and October 2022. Pretreatment genomic alterations were assessed in circulating tumor DNA (ctDNA) by Guardant360, while MRD was assessed 4 weeks after resection with a methylation-based ctDNA MRD assay (Guardant Reveal). Characteristics of pts who were MRD negative but relapsed later were analyzed. Results: Of 118 eligible pts enrolled, pretreatment ctDNA was detected in 99 (84%), 62 (53%) of whom had poor genomic profile, defined as a mutation in BRAF, RAS, PIK3CA, and/or SMAD4. Of 110 pts who underwent surgery, postoperative MRD was detected in 35 (32%). With a median follow-up time of 11.0 months (m), 37 pts recurred, of whom 14 were MRD negative and 23 MRD positive. MRD negative pts were more likely to develop lung metastases (64.3% vs. 30.4%, p=0.09) but less likely to have liver metastases (21.4% vs. 60.9%, p=0.03). Median recurrence-free survival (RFS) of MRD-negative relapsed pts was longer than that of MRD positive pts (8.6 m vs. 3.5 m; hazard ratio [HR], 0.28 [95% CI, 0.13-0.58]). Among MRD-negative pts with recurrence, risk factors most associated with recurrence were a history of lymph node metastases (LNM) (odds ratio [OR], 6.20 [95% CI, 1.28-30.1]) and poor pre-operative genomic profile (OR, 3.85 [95% CI, 1.08-13.70]). Among all resected pts, LNM (HR, 2.55 [95% CI, 1.10–5.89]), poor genomic profile (HR, 2.97 [95% CI, 1.29–6.85]), and MRD positivity (HR, 6.36 [95% CI, 2.96–13.64]) were significantly associated with shorter RFS in multivariate analyses. Conclusions: Pts with a history of LNM or poor pre-operative genomic profile were at risk of recurrence despite the absence of MRD after curative-intent resection of CRM. Clinical trial information: UMIN000042490.

Neoadjuvant pembrolizumab and lenvatinib in resectable mucosal melanoma: NeoPlus study update.

9580 Background: Combination therapy of anti-PD1 agent with VEGFR inhibitor is a promising therapeutic approach in unresectable or metastatic mucosal melanoma. We conducted this study evaluating neoadjuvant lenvatinib and pembrolizumab in pts with resectable mucosal melanoma. Methods: This was a single-arm, open-label, single-center, phase 2 study conducted from Sep 2021. Eligible pts were adults (18-75 yr) with histologically confirmed, resectable mucosal melanoma. Pts received lenvatinib 20mg qd and pembrolizumab 200mg q3w for 2 cycles, followed by surgery. Pembrolizumab (200mg q3w) continued post operatively for further 15 cycles. The primary endpoint was complete pathologic response (pCR). Secondary endpoints were Relapse free survival (RFS, time from surgery to any event), Overall survival (OS) and safety. Results: Between Sep 2021 and Apr 2023, 26 pts were enrolled, median age was 57 yrs(range: 49-75), 19 were female. Primary sites included: 11 female genital, 8 ano-rectal, 5 head & neck (1 nasal, 4 oral),2 esophageal. 15 pts (58%) were localized disease,11 (42%) were regional lymphatic disease. BRAF V600, NRAS or KIT mutations were presented in 1, 3 and 2 pts, respectively. 21 pts underwent surgery, 2 pts had a pCR (9.5%), 2 near PCR, 4 pPR, with a pathologic response rate of 38% (8/21,95%CI 18-62%). 5 pts did not proceed with planned surgery for pts preference. As of Dec 2023, 12 of 21 resected pts had relapsed (9/11 in female genital,2/4 in ano-rectal, 1/5 in head & neck). Median follow up time was 19.1 months (95%CI 13.7-24.5). Median RFS was 12.4 months (95%CI 4.0-20.8), no difference was observed among these primary sites (female genital: 6.6 months, ano-rectal: 14.1 months, head & neck: not reached). Median DMFS was not reached. IHC data of the resected tumor showed higher CD8+ T cells density in responders (R: pCR+near PCR+ pPR) than non-responders (NR: pNR) (p = 0.046). Tertiary lymphoid structures were detected in 9 pts. Most common TRAEs were hypertension (13, 50%), proteinuria (12, 46%), LDH increased (9,35%), hypothyroidism (8, 31%). Three pts experienced a dose reduction and 5 experienced a dose interruption due to an AE. No grade 4-5 toxicities were observed. Conclusions: Updated results confirmed that the combination of pembrolizumab plus lenvatinib as neoadjuvant therapy had moderate anti-tumor efficacy in resectable mucosal melanoma. Increased CD8+ T cell infiltration was observed in tumor with pathologic response, supporting further investigation in mucosal melanoma.

Prognostic value of BRAF and RAS mutations in radically resected patients (pts) with stage I-III melanoma: Preliminary results from a retrospective study.

e21567 Background: Although BRAF and RAS mutations in radically resected pts with stage I- II and III melanoma could have a prognostic value, conflicting evidences are still available. The present retrospective study was aimed to investigate this controversial issue. Methods: We retrospectively evaluated a consecutive series of 201 pts with stage I-III melanoma (AJCC 8th) who have undergone radical surgery from 2005 and 2010. For each pt we retrieved the clinical record and collected data concerning the clinical history. In addition, we evaluated the mutation status of somatic BRAF, KRAS and NRAS on a tissue sample obtained from primary surgery material. We describe the expression rate of such mutations and their relationship with pts’ survival outcomes. Results: To date they are evaluable data on 100 pts (M/F 62/38): the median age was 66 yrs (range 36-91), most of the pts was in stage I-II (66 %). The detected mutations is described in the table. Conclusions: From our preliminary results, it appears that BRAF and RAS mutations did not have prognostic value in the assessed population. The final report of the analyses carried on the whole population will increase the study ability to assess the role of these mutations in predicting the outcomes of radically resected stage I-III melanoma. [Table: see text]

A phase II/III study of camrelizumab plus apatinib as perioperative treatment of resectable hepatocellular carcinoma at intermediate-high risk of recurrence: Primary results of major pathologic response from phase II stage.

4126 Background: Surgical resection remains an important treatment strategy for patients (pts) with liver cancer. However, the 5-year recurrence rate is still 50-70% in surgically resectable pts. Intermediate-high risk factors of recurrence in HCC include single tumor size > 5 cm, multiple tumors, and microvascular invasion. The standardized perioperative regimen for resectable HCC has not been established. This study aimed to assess the efficacy and safety of camrelizumab plus apatinib (C+A) as a perioperative regimen in resectable HCC at intermediate-high risk of recurrence (Clinical trial: NCT04521153). Methods: In this multicentre, randomised, phase II/III study, eligible HCC pts (CNLC Ib-IIIa) were randomly assigned in a 1:1 ratio to treatment group and control group. Pts in treatment group received 2 cycles of C (200mg Q2W) plus A (250mg QD) followed by surgery and a post-surgical TACE. At least 6 cycles of sequential treatment of C (200mg Q3W) plus A (250mg QD) were performed after TACE. Pts in control group received surgical resection and a post-surgical TACE. Primary endpoint of phase III stage was 3-year EFS, of phase II stage was MPR (defined as less than 50% residual tumor) rate. In the phase II stage, futility analysis on a phase II outcome was performed after pts in treatment group completed surgical resection and pathological evaluation. If < 15% of pts achieved an MPR, or > 20% of pts had progression that precluded surgery, the study would not proceed to phase III stage. Results: In phase II stage, 60 pts were randomly assigned to treatment group, and 59 to control group. As of Nov 4, 2022, the last randomised pt underwent curatively surgical resection and pathological evaluation. The median age was 58 years (range, 21-75). 101(84.9%) were male, and 96 (80.7%) had HBV infection. In treatment group, 58 pts received neoadjuvant therapy, 52 completed 2 cycles of preoperative therapy and proceeded with planned resection. Surgery was aborted for 6 pts: 3 refused surgery, 2 deaths (1 for tumor rupture of HCC, 1 for immune related hepatitis), and 1 had protocol deviation. The MPR rates in the ITT population were 40% (24/60). Among them, 10% pts (6/60) had ≤ 5% surviving tumor cells in tumor bed. The MPR rate in pts who had surgical resection were 46.2% (24/52). 19.3% pts experienced ≥ 3 grade TRAEs, the most common of which were AST increased (5.3%), hypertension (5.3%), and ALT increased (3.5%). Conclusions: The phase II stage of the study did not meet the stopping criteria. Neoadjuvant camrelizumab plus apatinib therapy exhibits promising pathological response in HCC pts at intermediate-high risk of recurrence, with a tolerable safety profile. The phase III stage of the study is currently ongoing. Clinical trial information: NCT04521153 .

18F-fluorocholine PET/CT detects parathyroid gland hyperplasia as well as adenoma: 401 PET/CTs in one center.

During the past decade, 18F-fluorocholine (FCH) PET/CT has been continuously performed at Tenon Hospital (Paris, France) for the detection of hyperfunctioning parathyroid glands (PT). A cohort of 401 patients, deliberately referred for HPT since September 2012, has been analyzed. The aim of this real-life retrospective study was to determine the diagnostic utility of FCH in this setting, overall and in subgroups according to the type of hyperparathyroidism (HPT), the context of FCH in the imaging work-up and in the patient's history: initial imaging or persistence or recurrence after previous parathyroidectomy (PTX). The influence of the histologic type of resected PTs, hyperplasia or adenoma, on the preoperatory detection on FCH PET/CT has been studied as well. Four hundred one FCH PET/CTs were included in the cohort, performed in 323 patients with primary HPT (pHPT), including 18 with familial HPT (fHPT), and in 78 patients with secondary renal HPT (rHPT). The overall positivity rate in the 401 FCH PET/CTs was 73%. The PTX rate was twice greater in patients whose FCH PET/CT was positive than negative (73% vs. 35%). Abnormal PT(s) were pathology proven in 214 patients: only hyperplastic gland(s) in 75 cases and at least one adenoma in 136 cases; FCH PET/CT sensitivity was 89% and 92%, respectively. Similarly, there was no significant difference in patient-based sensitivity whether FCH PET/CT was performed as 1st line or later in the imaging work-up, or indicated for initial imaging or for suspicion of persistent or recurrent HPT. Gland-based sensitivity was significantly lower for hyperplasia than for adenoma (72% and 86%, respectively). The lowest gland-based sensitivity value was 65%, observed in case of hyperplasia and when FCH was performed late in the imaging work-up. FCH PET/CT correctly showed multiglandular HPT (MGD) in 36/61 proven cases, 59%. Results of ultrasonography (US) and 99mTc-sestaMIBI (MIBI) imaging were available in 346 and 178 patients, respectively. For both modalities, the corresponding sensitivity values were significantly less than those of FCH PET/CT (e.g., overall gland-based sensitivity 78% for FCH, 45% for US, 30% for MIBI) and MGD was detected in 32% of cases by US and 15% by MIBI. Although FCH PET/CT has been performed since 2017 as 1st line imaging for HPT at Tenon Hospital (Paris, France), a large majority of patients underwent prior US and/or MIBI in their preoperative work-up. Therefore, a selection bias is very likely, as most patients referred to FCH PET/CT had non-conclusive or discordant results of US and MIBI, explaining the low performance of those modalities in the present cohort compared to published results. Nevertheless, the superiority of FCH PET/CT over US and MIBI in detecting abnormal PTs reported in various comparative studies is definitely confirmed in this larger real-life cohort. The detection with FCH PET/CT of hyperplastic PTs was somewhat lower than that of adenomas but was better than using US or MIBI. The present results lead to recommend FCH PET/CT as the first line imaging modality in HPT when it is widely available or, if less available, at least in HPT with predominance of hyperplasia and/or MGD.

Perioperative chemoimmunotherapy with durvalumab for operable muscle-invasive urothelial carcinoma (MIUC): Primary analysis of the single arm phase II trial SAKK 06/17.

4515 Background: SAKK 06/17 investigated the addition of perioperative immunotherapy with the anti-PD-L1 antibody durvalumab (Durva) in the multimodality treatment of resectable MIUC. While most similar trials had a primary endpoint of pathological complete remission rate, this study evaluated the clinically more relevant primary endpoint of event-free survival (EFS) at 2 years (yrs). Methods: SAKK 06/17 was an open-label, single-arm phase II study including 61 cisplatin-fit patients (pts) with stage cT2-T4a cN0-1 operable MIUC. Pts received four cycles of neoadjuvant Cis/Gem q3w in combination with 4 cycles Durva 1500mg q3w followed by complete resection. Adjuvant Durva 1500mg q4w was given for 10 cycles or a maximum of 40 weeks. The primary endpoint was EFS at 2 yrs after neoadjuvant trial treatment (NAT) start. An event was defined as progression during NAT, appearance of metastases, locoregional recurrence after surgery or death from any cause. 58 pts were needed based on one-sided type I error 10% and power 80% for H1 EFS at 2 yrs ≥ 65% compared to H0 EFS at 2 yrs ≤ 50%. Secondary endpoints included pathological response, recurrence free survival after R0 resection (RFS), overall survival (OS) and safety. We report the primary analysis of the full analysis set (FAS, received at least one dose of Durva). Results: 61 pts were included between July 2018 and September 2019 at 12 sites. Median follow up is 28.1 months (95%CI 27.8-28.4). FAS consisted of 58 pts (79% male, median age 68 yrs) with bladder cancer (95%) or upper urinary tract/urethral cancer (5%). Clinical T2, T3, T4 stage was present at diagnosis in 69%, 21%, 10%, respectively, and 17% had cN1. Resection was performed in 53 pts (91%; 4 refused, 1 unresectable) with R0 resection in 52 pts (98%). 48 (91%) of resected pts started adjuvant Durva and 32 (67%) completed it. Pathological response < ypT2 ypN0 was achieved in 32 pts (18 pts ypT0 and 14 pts ypT1/a/is), corresponding to 60% of resected pts and 55% of the FAS. EFS at 2 yrs was overall 76.1% (one-sided 90% CI (lower bound): 67.6%; 95% CI 62.3% - 85.3%), for ypT1/a/is 92.9% and for ypT0 100%. RFS at 2 yrs after R0 resection (N=52) was 83.5% (95% CI 69.6% - 91.4%) and OS at 2 yrs for the FAS population was 87.3% (95% CI 73.8% - 94.1%). Grade 1, 2, 3, 4 adverse events attributed to Durva during overall treatment were 14%, 35%, 19%, 7%, respectively. Conclusions: The addition of perioperative Durvalumab to the standard of care for pts with resectable MIUC results in a high EFS, RFS and OS at 2 yrs, especially for pts with downstaging to <ypT2. The null hypothesis for the primary endpoint was clearly rejected. More in-depth analyses for biomarkers (PD-L1, ctDNA) will be presented at the meeting. Clinical trial information: NCT03406650.

P-297 Prognostic impact of primary tumor location on synchronous and metachronous colorectal liver metastases: A retrospective monocentric real-life analysis

Many studies have investigated the impact of primary tumor location (PTL) on the prognosis of colorectal cancer (CRC) patients. Our analysis aimed to evaluate the prognostic implications of PTL among patients (pts) with synchronous liver metastases (SM) and metachronous (MM) colorectal liver metastases (CRLM). We retrospectively reviewed the data of pts affected by CLRM from 2016 to 2021 at our institute. Overall survival (OS) and Progression-free survival (PFS) were investigated. 109 pts were included, median age 70 yrs (35-91), M/F= 66/43, RAS wt 37.6%, RAS mt 34.9%, 57.7% with left-sided colon cancer (LCC), 42.2% with right-sided colon cancer (RCC), 50.4% with only liver metastases (mets), 49.5% with hepatic + other mets, 21.1% underwent CRLM resection (R0=73.9%), 42.2% with SM-LCC, 27.5% with SM-RCC, 15.5% with MM-LCC and 14.6% with MM-RCC. SM were prevalent (n=76, 69.7%). The median duration of follow-up was 14 mos (1-98). The 1-yr and 2-yrs survival rates were higher in MM, MM-LCC, and all liver resected pts as listed below namely, respectively: 70.4% and 60.8% in all pts; 74.6% and 61.2% in LCC vs 65% and 61.8% of RCC (p=0.57); 72.5% and 67.7% in MM pts vs 69.5% and 57.5% of SM pts (p=0.63); 71.5% and 53.6% in resected SM-LCC pts vs both 66.7% of resected SM-RCC pts (p=0.95); both 84.6% in resected MM-LCC pts vs 62.5% and 54.7% of resected MM-RCC pts (p=0.23); 100% and 93.8% in pts undergoing liver resection vs 62.7% and 50.6% of pts with unresected liver (p=0.004); 64.9% and 43.9% in unresected SM-LCC pts vs both 62.5% of unresected SM-RCC pts (p=0.90); both 71.4% in unresected MM-LCC pts vs 53.8% and 43.1% of unresected MM-RCC pts (p=0.35). PTL had no influence on 2-yrs survival in all pts and OS in SM-RCC pts. The mOS in liver resected pts was higher in SM-LCC pts (21 vs 18 mos) and in MM-LCC pts (18.5 vs 15 mos). The best PFS in no liver resected pts was observed in the MM, SM-LCC, and in MM-LCC groups as follows: 8 months (mos) (95%CI=4-12) in all pts; 8 mos (95%CI=1-18) in LCC vs 8 mos (95%CI=4-12) of RCC (p=0.82); 11 mos (95%CI=8-14) in MM vs 5 mos (95%CI=1-19) of SM (p=0. 42); 10 mos (95%CI=7-13) of SM-LCC vs 7 mos of SM-RCC (95%CI=2-11) (p=0.59); 12 mos (95%=1-31) of MM-LCC vs 5 mos (95%CI=1-11) of MM-RCC (p=0.34). Our real-life study identified the timing of liver metastases as a prognostic factor and showed that pts with LCC and especially MM-LCC have the higher survival.

Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Updated final results of the randomized phase II AIO-NEONAX trial.

4133 Background: Perioperative chemotherapy (CTX) in resectable pancreatic ductal adenocarcinoma (PDAC) is still not considered standard of care and data are limited. The NEONAX trial examined gemcitabine (Gem) plus nab-paclitaxel (nab-P), in the perioperative or adjuvant therapy of resectable PDAC (NCCN criteria). Methods: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. 127 resectable PDAC patients in 22 German centers were randomized 1:1 to perioperative (2 pre- and 4 postoperative cycles, arm A) or adjuvant (6 cycles, arm B) of Gem (1000mg/m2) and nab-P (125mg/m2) on days 1,8,15 of a 28-day cycle. Results: We previously reported the primary endpoint disease free survival (DFS) at 18 mo. in the modified intention-to-treat (ITT)-population (defined as R0/R1 resected pts. that either started neoadjuvant (A) or adjuvant (B) CTX. The pre-defined DFS rate of 55% at 18 mo. was not reached in both arms (A: 32.2%, B: 41.4%). Here we present the final results of the secondary endpoints median overall survival (mOS), pN0-resection rate, perioperative morbidity/mortality and safety in the ITT-population. Most common grade ≥3 treatment emergent adverse events in the safety population were neutropenia (arm A 21.1%, arm B 12.3%), fatigue (arm A 8.8%, arm B 5.3%) and anemia (arm A 10.5%, arm B 1.8%). The most frequent post-/perioperative complications of all grades in pts. undergoing resection were infections (arm A: 24.4%, arm B: 8.8%), pancreatic fistulas (arm A: 14.6%; arm B: 13.3%) and bleedings (arm A: 9.7%; arm B: 6.7%). Perioperative mortality was 2.4% in the neoadjuvant and 6.7% in the upfront surgery setting. The median number of resected lymph nodes was comparable in both arms (A: n = 21, B: n = 26). The pN0-resection rate was 33.3% in the neoadjuvant/perioperative arm A and 29.5% in the upfront surgery arm B. R0 resection rates were 87.8% in arm A and 67.4% in arm B, respectively. Median OS as a key secondary endpoint in the ITT population was 25.2 mo. in arm A and 16.7 mo. for upfront surgery, a difference of 8.5 mo. This difference corresponds to a mDFS of 11.5 mo. in arm A and 5.9 mo. in arm B. 91.5% of pts. in arm A started and 84.7% completed neoadjuvant CTX but only 42.4% of pts. in arm B started adjuvant CTX. Conclusions: Perioperative treatment with Gem/nab-P was well tolerated and showed an encouraging mOS of 25.2 mo., this is well in the range of the data in SWOG 1505 (23.6 mo.) or PREOPANC (15.7 mo.). The corresponding mOS in the upfront surgery arm was 16.7 mo. The 8.5 mo. difference may be explained by the fact that many pts. in arm B did not receive adjuvant treatment whereas the vast majority of pts. in arm A completed at least preoperative CTX. Neoadjuvant/perioperative treatment is a promising novel option for pts. with resectable PDAC. The optimal treatment regimen is subject of current clinical trials. Clinical trial information: NCT02047513.

Early-onset pancreatic cancer: Defining contemporary presentation, treatment, and outcomes in the under 50 age group using real-world data.

533 Background: The incidence of pancreatic cancer is increasing in younger patients (pts). Early onset pancreatic cancer (EOPC) is reportedly diagnosed at a later stage, potentially compromising outcomes compared to later onset pts (LOPC). With recent gains in staging and neo/adjuvant regimens, we sought to elaborate on the characteristics of EOPC and LOPC in a contemporary real-world cohort. Methods: The PURPLE registry, a prospectively collected multi-site data set on consecutive pancreatic cancer pts was interrogated. Patient, tumor, treatment and outcome data were extracted for EOPC vs LOPC. EOPC were those diagnosed prior to age 50 and LOPC after age 50. Resectability status was per MDT consensus. Results: Of 1534 pts, 93 (6%) were EOPC (51% male) and 1442 (94%) LOPC (51% male). EOPC had better ECOG performance status (0-1: 95% vs 81%, Relative Risk [RR] 1.2, p < 0.001) and Charlson Comorbidity Index Score (0-2: 98% vs 28%, RR 3.5, p < 0.001). Primary tumor site (head/body/tail: 66%/11%/20% for EOPC and 68%/17%/14% for LOPC), and staging (resectable/borderline resectable/locally advanced/metastatic: 29%/16%/14%/41% for EOPC vs 28%/9%/21%/41% for LOPC) did not differ. 25 (93%) of EOPC and 320 (79%) LOPC resectable pts underwent resection (p = 0.13). 12 (80%) EOPC and 36 (26%) LOPC borderline resectable pts underwent resection (RR 3.0, p < 0.001). Resection margin status (R0 vs R1 vs R2) did not differ. Resected EOPC more frequently received neoadjuvant therapy (30% vs 9%, RR 3.2, p = 0.001). EOPC were more likely to receive palliative chemotherapy in the advanced/metastatic setting (77% vs 49%, RR 1.6, p < 0.001), and were more likely to receive first line (1L) FOLFIRINOX than gemcitabine-nab-paclitaxel (36% vs 18%, RR 2, p = 0.019). Median overall survival (OS) was superior for EOPC (24 vs 12 months, Hazard Ratio [HR] 0.55, p < 0.001). For resectable pts, relapse free survival (RFS) did not differ but OS was superior for EOPC (undefined vs 27.7 months, HR 0.26, p = 0.004). In borderline resectable pts, RFS was similar and OS only numerically superior for EOPC (31.2 vs 17.7 months, p = 0.20). For locally advanced disease, 1L progression free survival (PFS1) was similar and OS was superior for EOPC (27.8 vs 11 months, HR 0.40, p = 0.008). There was no difference in PFS1/OS for metastatic pts. Conclusions: EOPC are fitter, with similar stage at diagnosis as LOPC. EOPC are more likely to receive neoadjuvant chemotherapy and undergo resection when presenting with borderline resectable disease. EOPC receive more treatment and have superior OS, with RFS/PFS1 not statistically different to LOPC.

Randomized multicenter phase II/III study with adjuvant gemcitabine versus neoadjuvant/adjuvant FOLFIRINOX in resectable pancreatic cancer: The NEPAFOX trial.

406 Background: The outcome of pancreatic cancer remains poor. Few patients (pts) can be assigned to surgery and 80% of resected pts experience a relapse. Currently, adjuvant ctx is standard, but prognosis remains poor. FOLFIRINOX (FFX) is a SOC in metastatic and meanwhile in the adjuvant setting and may represent a valuable neoadjuvant option in resectable and borderline resectable stages. We initiated the NEPAFOX– trial in Germany to explore the efficacy of perioperative FFX. Methods: This is a multicenter randomized phase II/III trial. Recruitment of the trial was stopped after 40 patients (pts) due to poor accrual. Pts with resectable or borderline resectable adenocarcinoma of the pancreas without metastases were eligible. Eligible pts were randomized to (arm A) upfront surgery followed by adjuvant gemcitabine (1000 mg/m2) for 6 months or (arm B) perioperative FFX (irinotecan 180 mg/m2, oxaliplatin 85 mg/m2, 5-FU 400mg/m² bolus, 5-FU 2400 mg/m², sodium folinate 400 mg/m2) 4-6 cycles (8-12 weeks) pre and further 4-6 cycles post surgery. The primary endpoint is OS. Secondary endpoints include PFS, perioperative morbidity, mortality, and others. Results: 40 pts (42.5% female) were randomized over 3 years (05.03.2015 FPI - 23.03.2018 LPI), 21 in arm A, 19 in arm B. Age range was 46-84y, median age 64y.Before randomization, 76.2% of the pts in Arm A and 78.9% in Arm B were classified as primarily resectable the remaining pts as borderline resectable. Patients received in median 3 cycles in Arm A (range: 0-6) and 6 in Arm B (range: 1-12). Surgery was performed in 18 pts (85.7%) in Arm A and 11 (57.9%) in Arm B. Reasons for not conducting surgery were for Arm A patient´s wish (1 pt) and inoperability (2 pts), for Arm B early progressive disease (4 pts), death (1 pt), pneumonia (1 pt), and toxicities (1 pt). 13 (Arm A) and 5 (Arm B) pts had a R0-Resection. Perioperative morbidity occurred in 72.2% of operated pts in Arm A and 45.5% in Arm B. Median OS was 25.68 months in Arm A (6 events of death) and 10.03 months in Arm B (14 events) with HR 0.366 and p = 0.0337. Median PFS was 9.8 months in Arm A (12 events) and 6.64 months in Arm B (16 events) with HR 0.722 and p = 0.4099. Conclusions: Due to low pt numbers, the analyses for primary and secondary endpoints are not robust and only descriptive. Median OS for Gemcitabine- arm was in the line with literature data and better than for FFX, but pt/event numbers are too for conclusion. Only 11 out of 19 FFX pts underwent surgery, only 9 pts had pancreatic resection, indicating that pts should be extremely good selected before starting a neoadjuvant approach. According to CT or MRI pts of arm B were not more advanced regarding tumor staging. Nevertheless, there were no safety issues in the FFX arm regarding surgical complications, so neoadjuvant/ perioperative treatment approach seems to be feasible, subjected to the small number of pts in the study. Clinical trial information: NCT02172976.

Long-term outcomes of a prospective single institution study with multiagent chemotherapy and stereotactic body radiation therapy in locally advanced or recurrent pancreatic adenocarcinoma.

440 Background: We previously reported a multi-center study in which gemcitabine and stereotactic body radiation therapy (SBRT) were shown to be safe with outcomes comparable to chemoradiation in locally advanced pancreatic cancer (LAPC). This prospective clinical trial was developed to evaluate the efficacy of adding SBRT to multi-agent chemotherapy in LAPC. Herein, we report on the long-term survival outcomes. Methods: From 2012 to 2015, 48 patients (pts) were prospectively enrolled after multidisciplinary evaluation at a single high-volume pancreatic center. Pts received multi-agent chemotherapy (CTX) with modified mFOLFIRINOX (mFFX) or gemcitabine/abraxane followed by 5 fractions of SBRT (median 33 Gy; range, 25-33 Gy). At the time of fiducial placement, biopsies were obtained and DNA extracted for targeted sequencing using MSK-IMPACT. Kaplan-Meier curves were generated to compare survival outcomes by sub-group. Multivariate analysis (MVA) was performed to identify factors prognostic for survival. Results: 44 pts (91.7%) had LAPC disease and 4 (8.3%) had locally recurrent disease. The median follow-up interval was 21.5 months (mo) from diagnosis. CTX consisted of mFFX in 25 pts (52.1%) with 24 pts (50.0%) receiving therapy for a duration ≥4 mo. Of 44 pts with LAPC, 15 (34.1%) were surgically explored, and 11 (73.3%) achieved a margin-negative resection. From diagnosis and after completion of SBRT, respectively, the median overall survival (OS) was 21.6 (95% CI 16-29.7 mo) and 14.6 mo (95% CI: 11.6-23.0 mo); median progression free survival (PFS) was 13.2 (95% CI 11.9-18.1mo) and 6.4 mo (95% CI: 5-12.7 mo); median local PFS (LPFS) was 23.9 (95% CI 18.9-56.9 mo) and 15.8 mo (95% CI: 12.9-27.6 mo); and median distant metastasis free survival (DMFS) was 18.4 (95% CI 12.6-29.3 mo) and 8.5 mo (95% CI: 6.3-17.2 mo). Resected pts experienced better DMFS at 1-year (78% vs. 34%, p= 0.004) with an improved trend for 1-year OS (73% vs. 52%, p= 0.331). If CTX duration was ≥4 mo, 1-year OS (75% vs. 42%, p= 0.018), PFS (50% vs. 21%, p= 0.022), and DMFS (72% vs. 29%, p= 0.031) were significantly improved. In 44 LAPC pts, MVA confirmed ≥4 mo duration of CTX was associated with OS, PFS, and DMFS. Surgical resection was associated with improved DMFS, and CA19-9 level prior to SBRT was associated with PFS and LPFS. The most common mutations detected from biopsy specimens were KRAS (64.3%) , TP53 (50%), and SMAD4 (16.7%). Conclusions: In a prospective trial of pts with LAPC receiving multiagent CTX and SBRT, clinical outcomes were improved with longer durations of CT ( > 4 mo). A high proportion of LAPC pts underwent margin negative resection with favorable outcomes. Future studies should focus on which pts are most likely to benefit from SBRT and surgery following multiagent CTX. In pts who cannot undergo resection, escalated doses of SBRT may be indicated. Clinical trial information: NCT01781728.

Histopathologic Regression and Survival in RAS Wildtype Metastatic Colorectal Cancer Under First-Line Treatment – Subgroup Analysis of the VOLFI Trial (AIO-KRK-0109)

<i>Aim</i>: The VOLFI trial demonstrated an improved objective response rate through the addition of panitumumab to FOLFOXIRI in untreated all-RAS-wildtype mCRCs compared to FOLFOXIRI alone. In this subgroup analysis, we focused on histopathological response as a predictive marker for PFS. Additionally, we analyzed chemotherapy induced steatosis hepatitis (CASH) in both treatment arms. <i>Methods</i>: Histopathological response, CASH, sinusoidal obstructive syndrome, ballooning, steatosis, cholestasis, fibrosis and inflammation were determined in 14 resected liver metastasis. PFS was estimated using Kaplan-Meier method, the logrank test was used for the statistical comparison. The trial is registered with Clinical Trials. gov, NCT01328171. <i>Results</i>: Tissue of 14/18 resected pts. was evaluable. Median age was 57.5 yrs. (32–67), 7 male and 7 females. All primary tumors were located in the left colon. Molecular analysis detected one BRAF V600E mutation and one MSI-H tumor. Median treatment duration until resection were 7 cycles (3 – 12) panitumumab/mFOLFOXIRI and 9.5 cycles (7 - 11) FOLFOXIRI. 7 pts. achieved very good histopathological response corresponding to ≤20% vital tumor cells (panitumumab/ mFOLFOXIRI vs. FOLFOXIRI 2/5) and 7 pts. showed vital tumor cells >20% (panitumumab/mFOLFOXIRI vs. FOLFOXIRI 2/5). A very good histopathological response (residual tumor cells in proportion to the total tumor area ≤20%) showed a trend to an improved PFS in comparison to >20% (median PFS 12.40; 95% CI 6.43-51.22 vs. PFS 9.88; 95% CI 6.17-15.26 months). The severity of CASH was not increased by the addition of panitumumab or longer duration of chemotherapy. <i>Discussion</i>: In this analysis histopathological response seems to correlate with a better PFS after secondary metastasis resection. By analysis of liver toxicity, no relevant difference of CASH were detectable regarding panitumumab/mFOLFOXIRI vs. FOLFOXIRI or the duration of chemotherapy.

Long Term Follow-up of a Phase II Study of Autophagy Inhibition with Hydroxychloroquine (HCQ) and Preoperative (Preop) Short Course Chemoradiation (SCRT) Followed by Early Surgery for Resectable Ductal Adenocarcinoma of the Head of Pancreas (PDAC)

PDAC is highly dependent on autophagy, a metabolic process that renders cancer cells resistant to cytotoxic therapies. HCQ has been shown to be a potent inhibitor of autophagy, has preclinical activity, and clinical evidence of increased response rates. We evaluate the efficacy of concurrent and adjuvant HCQ with preop SCRT and adjuvant chemotherapy. Patients with radiographically resectable, biopsy-proven PDAC of the head were enrolled from 12/2011-09/2016 on this IRB-approved, NCI-sponsored clinical trial (NCT01494155). Eligibility included no CT involvement of SMA or celiac artery; adequate renal, hepatic and hematopoietic functions; and ECOG PS 0/1. Pts received either 5 Gy x 5 with protons or 3 Gy x 10 with photons concurrent with Cape 825 mg/m2 BID wk 1 and 2 M-F. HCQ was started at 400 mg po BID 1 wk prior to radiation through SCRT until the day before surgery. Surgery was performed 1-3 wks after completion of SCRT. Patients were recommended to receive 6 mo of gemcitabine-based chemotherapy after surgery. Pts resumed HCQ after discharge from surgery and continued until progression. Follow-up was performed every 3 months with CT scanning every 6 mo. 50 pts were enrolled on study and all are evaluable for this analysis. Median age- 69 (range 54-85), female- 24 pts (48%), pre-treatment CA19-9 median 69.5 U/mL (range <1-10235) Gr 3 toxicity was noted in 3 (6%) pts (vomiting-1, nausea-1, hyperglycemia-2). 50 pts completed SCRT. 47 pts underwent resection. Reasons for no resections were: metastatic disease-2, intercurrent illness- 1. 38 pts had R0 resection, 9 had R1 resection. 31/47 had positive nodes. 1 pt had no viable tumor at resection. Of the 47 resected pts, 10 pts remain on HCQ. Median follow up in 13 surviving pts is 51.6 months. mPFS is 13.0 mo, mOS 18.7 mo. OS-2 yr- 42,0% OS-4yr- 24.2%, PFS-2-yr 32.0%, PFS-4-yr- 19.8%. Most common sites of recurrence were liver (24%), lung (12%) and peritoneum (10%). HCQ with preop SCRT and adjuvant gemcitabine-based chemotherapy is well tolerated but did not meaningfully impact median OS. Further pathologic/correlative studies to identify long-term survivors and extreme responders are ongoing.

The role of primary tumor (PT) site as prognostic factor after resection of colorectal (CRC) liver metastases (LM): A mono-institutional cohort study.

4081 Background: Radical resection of LM is the only chance of cure for liver-only mCRC pts. Besides the evaluation of technical resectability, several factors must be taken into account for the evaluation of recurrence risk. Among them we should consider the Fong Risk Score and its modified version, including RAS/BRAF status (Brudvik’s score). Tumor sidedness is an important prognostic factor in CRC. The impact of PT site on the outcome of LM resection is still debated. Hence, we retrospectively analysed mCRC pts, underwent to radical LM resection at our Institution, investigating the impact of PT site on DFS and OS. Methods: Liver-only mCRC pts underwent to radical LM resection were included. The association of PT site with DFS and OS was evaluated. The following variables were collected: gender; age (≥ vs &lt; 75 years ); ECOG PS; CEA baseline level; PT site; RAS and BRAF status; mucinous histology; grading (G1-2 vs G3); RECIST response during preoperative treatment; resected PT; synchronous vs metachronous; number of LM; bilobar vs unilobar LM; LM diameter ≥ 5 cm; R0 vs R1 resection. Univariate and multivariate analyses for DFS and OS were performed. Results: A total of 463 liver-only mCRC pts underwent to radical LM resection were included. Seventy (15%) pts had a right-sided (r-s) tumor and 393 (85%) pts a left-sided (l-s) tumor. R-s CRC pts more often had RAS/BRAF mutations in comparison to l-s tumors (76% vs 37%; p &lt; 0.0001). Median DFS and OS was 13.1 and 41.6 months, respectively, in r-s CRC vs 16.0 (p = 0.65) and 62.2 months (p = 0.033), respectively, in l-s tumors. At the multivariate analysis no significant association with survival parameters was shown for tumor sidedness. At the multivariate analysis, R0 resection was independently associated both with better DFS and OS; RAS/BRAF wt CRC and resected PT were significantly associated with improved OS. Considering all wt CRC pts (N = 237), 14 (6%) pts had r-s tumor and 223 (94%) l-s tumor. No significant association of tumor sidedness with survival was shown (DFS r = 10.0 vs l = 16.0 months, p = 0.62; OS r = 40.3 vs l = 66.2 months, p = 0.12). Conclusions: Our results showed that a significant smaller proportion of r-s CRC underwent to radical LM resection, indirectly confirming its worse prognosis. Among radically resected pts, r-s CRC was associated to a shorter OS (significant) and DFS (not significant) compared to l-s CRC, but it was not confirmed at the multivariate analysis. We can conclude that right PT site should not be considered as a contraindication for radical LM surgery, when feasible.

Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17).

499 Background: Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care for patients (pts) with MIUC but relapse rates remain high. Immune checkpoint inhibitors have demonstrated efficacy in advanced urothelial carcinoma (UC). We hypothesize that the integration of the PD-L1 inhibitor durvalumab into perioperative management of MIUC improves outcome. Methods: SAKK 06/17 is an open label single arm phase II study including 61 pts. Operable MIUC cT2-T4a cN0-1 pts without contraindication for Cis were eligible. Four cycles of preoperative Cis/Gem q3w are administered in combination with 4 cycles Durva 1500mg q3w starting at cycle 2. Durva is continued after surgery q4w for 10 cycles. Primary endpoint is event free survival at 2 years. We report a preplanned interim analysis of the secondary endpoints safety, pathological complete remission ypT0 N0 (pCR,) and pathological response rate (PaR, defined as ≤ypT1N0) on the first 30 resected pts. Results: Among 34 eligible pts (27M, 7F; median age 70, range 41-81 years) included from 07/18 – 02/19, 33 pts (97%) had primary bladder cancer and 1 pt had upper tract UC. Clinical T2, T3, T4 and TxN1 stage were present at diagnosis in 68%, 18%, 15% and 15%, respectively. Four cycles of chemo-immunotherapy were completed per protocol in 34 pts (100%). No tumor progression was noted at preoperative restaging. AE related to Durvalumab were G3 in 5 pts (15%) and G4 in 3 pts (9%). Surgery was performed as planned in 30 pts (88%), 3 pts refused surgery and 1 pt had a frozen pelvis. Operation technique was open in 20 pts (67%) and laparoscopic/robot-assisted in 10 pts (33%). Postoperative complications included Clavien-Dindo III in 6 pts (20%) and IV in 2 pts (7%) with infections being most common (5 pts, 17%). pCR was found in 9 pts (30%) and additional 6 pts (20%) had ypT1/ypTis for a PaR of 50%. Conclusions: The combination of Cis/Gem and Durva as neoadjuvant treatment for MIUC is feasible with manageable toxicities and pCR and PaR rates in the expected range. The rate of postoperative complications warrants further close follow up. Clinical trial information: 2017-003565-10.

Perioperative complication rates following neoadjuvant therapy in pancreatic adenocarcinoma.

688 Background: Whether upfront resection or total neoadjuvant therapy is superior for the treatment of potentially resectable pancreatic adenocarcinoma (PDAC) remains controversial. The impact of neoadjuvant treatment on major perioperative complication rates for patients (pts) undergoing resection for PDAC is commonly debated. We hypothesized that rates would be comparable among patients receiving neoadjuvant chemoradiation (neo-CRT), neoadjuvant chemotherapy alone (neo-CHT), or upfront surgery. Methods: This is a retrospective study of 208 pts with PDAC who underwent resection within a multidisciplinary pancreatico-biliary program at an academic tertiary referral center between 2011-2018. Data were abstracted from the medical record, an institutional cancer registry and NSQIP databases. Outcomes were assessed using χ2, Fisher’s exact test and two-tailed Student’s t-tests. Results: 208 pts were identified: 33 locally advanced, borderline or upfront resectable pts underwent neo-CRT, 35 borderline or resectable pts underwent neoadjuvant-CHT, and 140 resectable pts did not undergo neoadjuvant therapy. There were no statistically significant differences in major perioperative complication rates between groups. Overall rates were 36.4%, 34.3%, and 26.4% for pts who underwent neo-CRT, neo-CHT alone, or upfront resection, respectively (p = 0.38). No significant difference were observed in complication rates (35.3% v. 26.4%; p = 0.19) or median hospital length of stay (10 days v. 10 days; p = 0.87) in pts who received any neoadjuvant therapy versus upfront resection. There were two perioperative deaths in the neo-CRT group (6.1%), zero in the neo-CHT group, and four in the upfront resection group (2.9%); p = 0.22. Conclusions: There were no significant differences in major perioperative complication rates, hospital length of stay, or post-operative mortality in pts who underwent neoadjuvant therapy (neo-CRT or neo-CHT alone) versus upfront surgery. Notably, neo-CRT had comparable perioperative complication rates to neo-CHT alone, which suggests neoadjuvant radiation therapy may not pose additional surgical risk.

Patterns of disease, treatment, and outcomes of esophageal cancer arising within a previous radiation treatment field.

328 Background: Esophageal cancer arising within a previous radiation treatment field (ECRF) is rare. The patterns of disease, treatment and outcomes in these patients (pts) have not been well characterized. Methods: A retrospective analysis was performed for pts treated for esophageal cancer at the Princess Margaret Cancer Centre from 2002-2016. Electronic medical records of all pts with a histologic diagnosis of esophageal cancer occurring within the field of previous radiotherapy were reviewed. The Kaplan-Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Results: Of 31 ECRF pts identified, the most common prior cancer was head and neck (45%), median radiation (RT) dose 50Gy, median time to diagnosis of esophageal cancer 12 years. Features at diagnosis of ECRF included: median age 71 years, 58% male, 87% with performance status (PS) 0-1, 77% squamous cell carcinoma, 19% stage IV. Treatment intent was curative in 16 pts, palliative in 15 (Table). Reasons for palliative treatment were: 40% metastatic, 53% comorbidities/PS, 7% anatomic factors. Of resected pts, 36% had a pT1-2 tumour, 55% pN0, 69% R0. For curative pts, median PFS was 26.2 months (95%CI 10.9-34.4) with a 3 year PFS rate of 35% (95% CI 15-81). Median OS for curative pts was 26.4 months (95%CI 17.8-105.5) with a 3 year OS rate of 43% (95% CI 22-83). Most palliative pts were unable to have chemotherapy due to comorbidities and PS. Median OS for palliative pts was 9.5 months (95% CI 3.6-15.4). Conclusions: Most ECRF pts presented with earlier stage disease; however, more than a third of these could not have aggressive curative treatment due to comorbidities and/or PS. Most curative pts had surgery alone. Few palliative pts had chemotherapy, largely due to poor clinical status. Our data suggest that outcomes in both curative and palliative ECRF pts may be limited by the ability to tolerate standard of care treatments. [Table: see text]

Survival after secondary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (CELIM, FIRE-3).

e15025 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term overall survival (OS) and potential cure after complete hepatic metastasectomy. The appropriate postoperative treatment strategy is still controversial. L-BLP25 as antigen-specific cancer vaccine targeting mucin 1 (MUC1) was recently evaluated as adjuvant therapy in mCRC pts after R0/R1 LLD resection (LICC trial, NCT01462513). Here we compared the LICC surveillance program and efficacy results for secondarily resected LLD pts versus historical controls, i.e. the CELIM trial (Folprecht et al, Ann Oncol 2014) of potentially resectable LLD mCRC pts and a FIRE-3-LLD subgroup (Holch et al, Int J Cancer 2018). Methods: LICC, CELIM and FIRE-3-LLD subgroup pts with stage IV mCRC limited to liver metastases who underwent hepatic resection (R0 or R1) were compared regarding pts characteristics, surveillance and efficacy outcome. LICC pts received adjuvant L-BLP25 or placebo after secondary LLD resection as 8 weekly doses, followed by 6 week maintenance intervals and tight surveillance until recurrence or a maximum of 2 years. Results: In LICC, 41 /121 pts (33.9%) were secondarily resected, and R0 resection was achieved in 31 pts (75.6%). In CELIM, 36/106 pts (34%) with primary unresectable LLD were secondarily R0 resected. In FIRE-3-LLD, secondary resection was feasible for 29/133 pts (21.8%). After R0 resection, median recurrence free survival (mRFS) was 8.9 months in LICC, 9.9 months in CELIM and 11.5/ 12.4 months in FIRE-3-LLD in either treatment arm. In the LICC trial, median overall survival (mOS) in secondarily resected pts was 65.1 months, with 38.3 months for the R1 and is not yet reached for the R0 subgroup. In CELIM, mOS was 53.9 months for R0 resected pts. In FIRE-3-LLD, after secondary resection mOS was 56.2 months. Median age was about 5 years less in LICC. Further details will be presented. Conclusions: Secondary resected pts of LICC, CELIM and FIRE-3 showed impressive median OS with better OS for LICC and a younger patient cohort. The established tight LICC surveillance program after surgery might have had a positive impact on survival. Clinical trial information: LICC: NCT01462513; FIRE-3: NCT00433927; CELIM: NCT00153998.

Survival after primary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (FFCD ACHBTH AURC 9002 trial and EORTC Intergroup trial 40983).

e15019 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term survival and cure after hepatic metastasectomy. The optimal treatment after primary liver resection remains controversial. Here we compare results from the LICC trial with historical controls, the FFCD ACHBTH AURC 9002 trial (FFCD; Portier et al., 2006) and the EORTC Intergroup trial 40983 (EORTC; Nordlinger et al., 2008, 2013). The three trials investigated pts with mCRC LLD who underwent primary hepatic resection. Methods: LICC, FFCD and EORTC were compared regarding pts characteristics, treatment, surveillance and efficacy outcomes. LICC pts received the adjuvant antigen-specific cancer vaccine tecemotide (L-BLP25) or placebo after primary LLD resection for up to 2 years. The FFCD trial compared postoperative 5-FU/leucovorin and the EORTC trial perioperative FOLFOX versus surgery alone. Results: Primary resected pts in LICC (n = 80; R0 n = 76), FFCD (R0 n = 171; postoperative chemotherapy n = 86) and EORTC (n = 364) showed different pt characteristics concerning median age (60, 63 and 63 years) and rate of synchronous metastases (46.8%, 27.9% and 34.0%). In LICC, &gt; 5 liver metastases were resected in 11.6% of pts, in FFCD and EORTC all eligible pts had &lt; 5 liver metastases resected. In contrast to EORTC, LICC and FFCD had a close surveillance until recurrence or a maximum of 2 years. Median OS (mOS) in LICC was not yet estimable in primary resected pts (tecemotide arm: 62.8 months; placebo arm: not yet estimable). In the FFCD and the EORTC trial, mOS was 62.1 and 61.3 months, respectively. Further details will be presented. Conclusions: Despite unfavorable disease characteristic in LICC compared with the earlier EORTC and FFCD studies, primary liver resection without adjuvant chemotherapy led to surprisingly good survival outcomes. Improvements in imaging-based pt selection and liver resection techniques might in part explain our finding. Surgery alone appears to be an option for selected pts with resectable LLD. Better systemic chemo(immune-)therapy may have also contributed to the OS benefit. Clinical trial information: LICC: NCT01462513; EORTC: NCT00006479; FFCD: not registered.