Cycles Of FOLFOX Research Articles

Induction FOLFOX prior to CROSS chemoradiotherapy and surgery in patients with locally-advanced esophageal and gastroesophageal junction cancer: A phase II study.

327 Background: In the CROSS trial, neoadjuvant chemoradiotherapy (CRT) prior to surgery for esophageal (E) and gastroesophageal junction (GEJ) cancers was found to improve survival. However, 10-year data did not show benefit in reducing isolated distant metastases. Addition of full-dose induction chemotherapy (CT) prior to CRT could provide early systemic disease control in addition to enhanced local control. We evaluated induction CT with FOLFOX followed by CRT and surgery in patients with E/GEJ cancers. Methods: This single-arm, phase II clinical trial investigated trimodality therapy in clinically staged II/III resectable cancers of the E/GEJ (NCT03110926). Treatment schedule was: 6 weeks of mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) followed by 5.5 weeks of CRT with weekly paclitaxel and carboplatin and 41.4-45 Gy of radiation (RT) and surgery. Primary endpoint was 2-year relapse-free survival (RFS) measured from time of surgery to date of first recurrence or death and was calculated by the Kaplan-Meier method. Overall survival (OS) and key pathologic findings were secondary outcomes. Results: In total, 41 patients enrolled with mean age of 63.1 years; 78% were male. Almost all (95%) were adenocarcinoma. Median duration of follow-up was 2.08 years. Most primary tumors were located in the GE junction (68.3%). Treatment was well tolerated: 95% patients completed all FOLFOX cycles, 98% received the pre-specified RT dose, and 36 of 41 (87.7%) went on to have surgery (1 elected observation after complete clinical response). R0 resection occurred in 97% of those that went on to have surgery. At least partial pathologic response was found in 30 of 36 (83.3%); 8 of 36 (22%, CI 10.1-39.2%) had a pathologic complete response (pCR) and 20 of 36 (55%) had pCR or near-complete response (NCR). At the time of analysis, 2-year RFS was 71.5% (CI 52.1-84.2) and the median RFS was 3.1 years; median OS was not reached. At time of follow-up, 85% (17 of 20) of those with NCR and PCR were relapse-free. Conclusions: Our study demonstrates a high treatment completion rate when FOLFOX was administered prior to CRT and surgery for E/GEJ cancers. Almost all patients had R0 resection and over half had NCR or pCR response. Short-term follow-up RFS and OS demonstrate promising efficacy for this approach in a sample almost exclusively of adenocarcinoma tumors. Strategies to implement induction FOLFOX or FLOT either with or without CRT should continue to be explored in larger studies. Clinical trial information: NCT03110926.

Survival outcomes associated with completion of adjuvant oxaliplatin-based chemotherapy for stage III colon cancer: A national population-based study.

The impact of cycle completion rates of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer in real-world practice is unknown. We assessed its impact, and that of treatment modification, on 3-year cancer-specific mortality. Four thousand one hundred and forty-seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3-year cancer-specific mortality was performed according to completion of <6, 6-11, or 12 5-fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4-7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital-level characteristics. Median age was 64 years. Thirty-two per cent of patients had at least one comorbidity. Forty-two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer-specific mortality was higher in patients completing <6cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56-3.03] or 6-11 cycles (sHR 1.40; 95% CI 1.09-1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer-specific mortality was higher in patients completing <4cycles (sHR 2.02; 95% CI 1.53-2.67) or 4-7cycles (sHR 1.63; 95% CI 1.27-2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer-specific survival in real-world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.

Oxaliplatin and 5-Fluorouracil in Advanced Well-Differentiated Digestive Neuroendocrine Tumors: A Multicenter National Retrospective Study from the French Group of Endocrine Tumors

Introduction: Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs); however, the available data are limited. Our aim was to assess the efficacy of FOLFOX (association of 5-fluorouracil with oxaliplatin) in a large series of patients with advanced digestive NETs. Methods: All patients with advanced digestive well-differentiated NETs treated with at least 3 cycles of FOLFOX between January 2004 and December 2018 in 12 centers from the French Group of Endocrine Tumors were included. Tumor response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria, progression free survival (PFS), and overall survival, as well as prognostic factors, were analyzed retrospectively. Results: One hundred fifty-five patients were included. Primary tumor locations were pancreas (n = 89), small intestine (n = 40), unknown with no evidence for lung primary (n = 13), stomach (n = 7), and rectum (n = 6). Median Ki-67 was 10%, and 65% of the tumors were grade 2. The partial response rate was 30% for pancreatic NETs, 12.5% for small intestine NETs, 38.5% for unknown primary NETs, 14% for gastric NETs, and 17% for rectal NETs. Significant prognostic factors for poor PFS after FOLFOX were progressive disease at the beginning of treatment (hazard ratio [HR] = 1.83, p = 0.007), hepatic involvement superior to 50% (HR = 2.67, p = 0.0001), and rectal primary tumor location (HR = 2.6, p = 0.0036). Among pancreatic NETs, insulinomas had a better median PFS (22 months) than other pancreatic NETs (9 months, p = 0.026) and showed a high rate (8/9) of serum glucose normalization. Conclusions: FOLFOX shows a promising antitumor activity in advanced digestive NETs. Rapid symptomatic response is observed in metastatic insulinomas.

Real-world survival outcomes associated with completion of adjuvant chemotherapy for stage III colon cancer.

3596 Background: The optimal duration of adjuvant combination chemotherapy administered to patients with stage III colon cancer is debated. Our study assessed the effect of completed chemotherapy cycles on 3-year colon cancer-specific mortality, as well as the effect of dose reduction and early discontinuation of oxaliplatin in patients with 100% completion, within a real-world population. Methods: 4,147 patients undergoing major resection between 01 June 2014 and 30 April 2017 with pathological stage III colon cancer in the English National Health Service were identified. Chemotherapy data were obtained from linked administrative hospital records and a national chemotherapy dataset. Patients were stratified according to completion of &lt; 50% ( &lt; 6 FOLFOX cycles or &lt; 4 CAPOX cycles), 50-92% (6-11 FOLFOX cycles or 4-7 CAPOX cycles) or 100% of cycles (12 FOLFOX cycles or 8 CAPOX cycles). Competing-risk regression analysis for 3-year colon cancer-specific death was performed with adjustment for patient, tumour and hospital-level characteristics to estimate subdistribution hazard ratios (sHR) as a measure of relative risk. Results: Patients included within our study were less fit and had increased rates of high-risk disease (T4 and/or N2 pathological staging) compared to the IDEA study. For FOLFOX, the 3-year cumulative incidence of colon cancer-specific death in patients completing 100% of cycles was 15.1% (95% CI, 12.8% to 17.6%), 18.2% (95% CI, 15.3% to 21.3%) for 50-92% of cycles and 26.4% (95% CI, 20.6% to 32.5%) for &lt; 50% of cycles. For CAPOX, this was 12.0% (95% CI, 10.2% to 14.0%) for 100% completion of cycles, 18.2% (95% CI, 15.6% to 21.0%) for 50-92% of cycles, and 19.8% (95% CI, 15.8% to 24.1%) for &lt; 50% cycles. Compared to 100% completion of FOLFOX cycles, colon cancer-specific death was higher in patients recorded as completing &lt; 50% (sHR 2.17; 95% CI, 1.56 to 3.03; P = &lt; 0.001) and 50-92% of FOLFOX cycles (sHR 1.40; 95% CI, 1.09 to 1.78; P = 0.007). Compared to 100% completion of CAPOX cycles, colon cancer-specific death was higher in patients recorded as completing &lt; 50% (sHR 2.02; 95% CI 1.53 to 2.67; P&lt; 0.001) and 50-92% of CAPOX cycles (sHR 1.63; 95% CI 1.27 to 2.10; P&lt; 0.001). Dose reduction and early discontinuation of oxaliplatin did not have a statistically significant effect on mortality. Conclusions: Patients within the real world setting were more likely to have poor prognostic factors. Those who completed adjuvant chemotherapy for stage III colon cancer had improved survival rates regardless of dose reduction or early discontinuation of oxaliplatin.

Association of genomic characterization with clinical benefits of anti-PD-1 antibody combined with FOLFOX as neoadjuvant therapy on locally advanced gastric or gastroesophageal junction adenocarcinoma.

e16025 Background: Anti-PD-1 antibody combined with chemotherapy showed promising efficacy in gastric adenocarcinoma. However, little is known about biomarkers that identify clinical response. Here, we focus on genomic alteration patterns to predict response of neoadjuvant immunotherapy in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). Methods: Patients with locally advanced GC/GEJC were received 4 cycles of FOLFOX plus anti-PD-1 antibody (camrelizumab) as neoadjuvant therapy in the study. We prospectively conducted whole exome sequencing (WES) in paired biopsy specimens from enrolled patients at baseline. According to Tumor Regression Grading (TRG) assessment by postoperative pathology, patients were classified into group A (TRG0 &amp; TRG1) and group B (TRG2 &amp; TRG3). Results: We eventually performed WES in 23 patients who had adequate available tumor tissues. The clinical characterizations were not significantly different between two groups. All 23 cases were microsatellite stable (MSS). Alterations of AHNAK2 (50.0%/6.67%), TG (50.0%/6.67%), CTNNB1 (37.5%/0.0%) and ZFHX2 (37.5%/0.0%) significantly enriched in group A (n = 8) compared to group B (n = 15).Furthermore, we inspecting 10 hallmark oncogenic pathways, alterations of WNT pathway also occurred more frequently in group A than those of group B. Genomic alterations in WNT pathway were identified in 5 of 23 cases (21.74%), of which the most frequently mutated genes were CTNNB1 (13.04%), LRP5 (8.69%) and RNF43 (8.69%). Tumor mutation burden (TMB, p = 0.357), whole genome duplication (WGD) status (p = 0.667), copy number variant burden (p = 0.825), fraction of loss of heterozygosity (LOH) in chromosome level (p: 0.07-1), tumor neoantigen burden (TNB) (p = 0.65), HLA type (p: 0.49-1) and HLA LOH status (p: 0.37-1) were not significantly associated with neoadjuvant therapy response. Conclusions: Aberrant activation of WNT pathway was reported to be associated with immune evasion. Our study demonstrated that CTNNB1/WNT-pathway-mut may be a promising predictor for clinical response of neoadjuvant immutherapy in GC/GEJC. Clinical trial information: NCT03939962.

Using randomized trial data to estimate effects of complex treatment regimens in real-world patients.

e18706 Background: Real-world patients often differ from trial participants in prognostic factors such as age, sex, and cancer substage. New methods combine covariate data from real-world patients (the “target population”) with outcome and covariate data from a trial to estimate treatment effects in the target population that take these differences into account. With some assumptions, these methods can also estimate outcomes under treatment regimens not studied in the trial such as “what if we only gave six cycles of chemotherapy?” or “what if patients all perfectly followed a protocol?” Methods: Data from the MOSAIC trial of 5-fluorouracil (5FU) vs oxaliplatin + 5FU (FOLFOX) were combined with covariate data from a target population of stage III colon cancer patients in the US Oncology Network meeting trial eligibility criteria. We used weighting and G-computation to estimate five-year mortality and treatment-related paresthesia risk in the target population for four regimens: treatment with up to 12 cycles of 5FU, if providers used their discretion on dose reductions and delays (5FU-MD); up to 12 cycles of FOLFOX with similar physician discretion (FOLFOX-MD); up to 6 cycles of FOLFOX, with providers perfectly following a strict and specific protocol of dose reductions and delays (6-cycle FOLFOX-P, “P” for “per protocol”); and up to 12 cycles of FOLFOX, following the same strict protocol (12-cycle FOLFOX-P). Results: Tablepresents five-year all-cause mortality and paresthesia risk under each regimen in the stage III target population estimated from the models built in trial participants. Paresthesia risk increased with cumulative oxaliplatin dose. Estimated 5-year mortality was lowest with 12-cycle FOLFOX-P. Conclusions: In a target population of US Oncology Network patients with stage III colon cancer, strict protocols of 12 cycles of FOLFOX were predicted to improve survival compared to strict 6-cycle FOLFOX regimens or less strict 12-cycle FOLFOX and 5FU regimens at the cost of substantial increases in side effects. While estimates of risk differences in 5-year mortality were imprecise, combining trial and real-world data and then using weights and G-computation allowed estimation of benefits and harms of multiple regimens in a clinically relevant patient population.[Table: see text]

Isolated splenic metastases from colon cancer: clinical observations

Isolated splenic metastases from colorectal cancer after radical surgical treatment are quite rare. This frequency of metastases is explained by the anatomical, functional and immunological characteristics of the spleen. The literature usually describes single clinical cases followed by accompanied systematic analysis and discussion. Most of the cases are asymptomatic and are accidentally diagnosed, during different types of imaging tests, including increased levels of tumor markers. The progression free survival was 3 144 months after surgical treatment of the primary tumor in most of the patients. By the nature of the lesion, metastases can be synchronous and metachronous, as well as solitary and multiple.&#x0D; Aim. To discuss two clinical observations of isolated splenic metastases in patients after left colic flexure cancer surgical treatment.&#x0D; Materials and methods. We observed 2 female patients, 68 and 70 years old, with isolated splenic metastatic after left colic flexure cancer radical surgical treatment.&#x0D; Results. Both cases are considered to be metachronous and the interval of absence of disease manifestations are 21 and 10 months, respectively. The patients with stage IIB and IIC left colic flexure cancer underwent left hemicolectomy followed by adjuvant polychemotherapy using regimen with 6 cycles of FOLFOX. The histological study revealed a moderately differentiated adenocarcinoma with invasion into all layers of the wall and into the surrounding tissue. There were no lymph node metastases. In the course of dynamic observation, during the next examination with the help of ultrasound examination we revealed splenic metastasis, and confirmed this using positron emission tomography/computed tomography. The disease was without clinical picture. The time interval after the surgery before diagnosis was 21 and 10 months, respectively. Surgery was performed in the volume of splenectomy. Isolated splenic metastases in the absence of other manifestations of the disease were found intraoperatively. The histological study showed the splenic metastasis of the same type of cancer as the primary tumor. The polychemotherapy using regimen with 6 cycles of XELOX was performed during the postoperative period. Patients are alive without signs of the disease over the period of 5 and 26 months, respectively.&#x0D; Conclusion. Isolated splenic metastases are extremely rare, more often when the primary tumor is located in the left side of the colon. The showed cases illustrate the need and importance of the monitoring the patients after surgical treatment for colon cancer. The use of positron emission tomography/computed tomography helps to understand the real prevalence of the tumor process, without using invasive methods. The surgery in the volume of splenectomy followed by chemotherapy are the main therapeutic options. In one clinical case, the metastases were multiple, and in the other one was solitary metastasis. Patients are alive without signs of the disease over the period of 5 and 26 months, respectively.

Perioperative Systemic Therapy vs Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Alone for Resectable Colorectal Peritoneal Metastases

To date, no randomized clinical trials have investigated perioperative systemic therapy relative to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) alone for resectable colorectal peritoneal metastases (CPM). To assess the feasibility and safety of perioperative systemic therapy in patients with resectable CPM and the response of CPM to neoadjuvant treatment. An open-label, parallel-group phase 2 randomized clinical trial in all 9 Dutch tertiary centers for the surgical treatment of CPM enrolled participants between June 15, 2017, and January 9, 2019. Participants were patients with pathologically proven isolated resectable CPM who did not receive systemic therapy within 6 months before enrollment. Randomization to perioperative systemic therapy or CRS-HIPEC alone. Perioperative systemic therapy comprised either four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles. Proportions of macroscopic complete CRS-HIPEC and Clavien-Dindo grade 3 or higher postoperative morbidity. Key secondary outcomes were centrally assessed rates of objective radiologic and major pathologic response of CPM to neoadjuvant treatment. Analyses were done modified intention-to-treat in patients starting neoadjuvant treatment (experimental arm) or undergoing upfront surgery (control arm). In 79 patients included in the analysis (43 [54%] men; mean [SD] age, 62 [10] years), experimental (n = 37) and control (n = 42) arms did not differ significantly regarding the proportions of macroscopic complete CRS-HIPEC (33 of 37 [89%] vs 36 of 42 [86%] patients; risk ratio, 1.04; 95% CI, 0.88-1.23; P = .74) and Clavien-Dindo grade 3 or higher postoperative morbidity (8 of 37 [22%] vs 14 of 42 [33%] patients; risk ratio, 0.65; 95% CI, 0.31-1.37; P = .25). No treatment-related deaths occurred. Objective radiologic and major pathologic response rates of CPM to neoadjuvant treatment were 28% (9 of 32 evaluable patients) and 38% (13 of 34 evaluable patients), respectively. In this randomized phase 2 trial in patients diagnosed with resectable CPM, perioperative systemic therapy seemed feasible, safe, and able to induce response of CPM, justifying a phase 3 trial. ClinicalTrials.gov Identifier: NCT02758951.

Efficacy of FOLFOX Chemotherapy in Metastatic Enteropancreatic Neuroendocrine Tumors.

FOLFOX (5-Fluorouracile and oxaliplatin) exhibits promising activity in advanced well-differentiated neuroendocrine tumors (NETs). This retrospective study aimed to analyze the outcome of metastatic enteropancreatic NETs patients treated with FOLFOX. We retrospectively identified patients treated with FOLFOX for NETs of enteropancreatic or unknown origin among those referred to our Regional Multidisciplinary Tumor Board. Among 48 patients, most often pancreatic NETs (n=33, 68.8%), the median Ki67 index was 10%. The median number cycle of FOLFOX was 6 and median follow-up was 34.8 months. Disease control rate (DCR) was 83.3%. Median PFS and OS were 12.6 and 29.4 months respectively. Median chemotherapy break was 14.1 months. No significant difference was observed between PFS and the following criteria: Ki67 index, primary tumor site, alkaline phosphatase levels, primary tumor surgery and 18F-FDG PET positivity. FOLFOX exhibits a high DCR and a short duration of treatment with a relative long chemotherapy break in patients with metastatic enteropancreatic NETs.

CORONARY VASOSPASM ASSOCIATED WITH 5-FLUOROURACIL CHEMOTHERAPY

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: 5-Fluorouracil (5FU) is the third most commonly used chemotherapeutic agent in the treatment of solid malignancies, particularly colorectal and pancreatic neoplasms. (1,2) Coronary vasospasm associated with 5FU is a known complication. (3) Cardiotoxicity occurs in 1% to 18% of patients receiving 5FU, and the incidence of this complication is on the rise.(4) The objective of this report is to highlight the characteristics of this uncommon complication. CASE PRESENTATION: A 66-year-old male with a past medical history of coronary artery disease status-post 4-vessel coronary artery bypass graft surgery and stage 4 colon adenocarcinoma with metastasis to the liver, presented to the emergency department (ED) with complaints of sudden onset of burning deep sub-sternal chest pain with no radiation. The chest pain began approximately eight hours after his first round of 5FU, leuocorin and eloxatin (FOLFOX) chemotherapy. In the ED he was given aspirin and heparin. EKG was concerning for ST-segment elevation myocardial infarction in the inferior leads. Troponins were negative (<0.01). A subsequent left heart catheterization revealed patent grafts and normal coronary arteries. An echocardiogram showed no acute wall motion abnormalities and an ejection fraction of 65%. The 5FU was discontinued and the patient’s chest pain improved. He was discharged with sublingual nitroglycerin and diltiazem. Two weeks later, the patient returned with similar chest pain after his second cycle with 5FU, leuocorin and eloxatin (FOLFOX). The symptoms of his coronary artery vasospasm were believed to be due to 5FU chemotherapy. He was further instructed to go to the cardiovascular ICU to receive nitroglycerine infusions before each cycle of FOLFOX. Unfortunately, the patient expired two months after starting chemotherapy; from cardiopulmonary arrest secondary to sepsis. DISCUSSION: This is a case of a 66-year-old male with a past medical history of coronary artery disease and stage 4 colon adenocarcinoma on 5-Fluorouracil, leuocorin and eloxatin (FOLFOX) chemotherapy presenting for coronary vasospasm likely from 5-Fluorouracil. Cardiotoxicity related to 5FU is poorly understood. Leading theories of the mechanism of 5FU-induced coronary vasospasm seem to involve 5FU's modification of smooth muscle tone. (5,6) Patients on 5FU with coronary vasospasm may have ECG findings suggestive of occlusion, (3) similar to our patient. Treatment of affected patients is determined by confirmation of 5FU as the definitive cause of the coronary vasospasm, as well as the requirement of 5FU as the only suitable chemotherapeutic agent. If possible, care providers should consider switching to an acceptable chemotherapeutic substitute. CONCLUSIONS: In conclusion, consideration should be given for patients with coronary artery disease starting 5-Fluorouracil chemotherapy. Reference #1: 1. Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 2000; 18: 299-313. 2. Myers CE. The pharmacology of the fluoropyrimidines. Pharmacol Rev 1981; 33: 1-15. 3. de Forni M, Malet-Martino MC, Jailais P, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. Clin Oncol 1992; 10: 1795-1801. 4. Lestuzzi C, Vaccher E, Talamini R, et al. Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk. Ann Oncol 2014; 25: 1059-1064. 5. Bonetti PO, Lerman LO and Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Throb Vasc Biol 2003, 23: 168-175. 6. Reddy KG, Nair RN, Sheehan HM, et al. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for artherosclerosis. I Am Coll Cardio! 1994; 23: 833-843. DISCLOSURES: No relevant relationships by Ahmad ababneh, source=Web Response No relevant relationships by HANAD BASHIR, source=Web Response No relevant relationships by Ahmad JABRI, source=Web Response No relevant relationships by Gauranga Mahalwar, source=Web Response

94P - NORTH/HGCSG1003: North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer: Final analysis

BackgroundFOLFOX and CAPOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for Japanese patients(pts) with resected stage III colon cancer (UMIN ID: 000004590). MethodsThis phase II study enrolled patients with resected stage III colon cancer. Patients received 12 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 5-year OS rate. ResultsFrom Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age; 65(33-84), Male/female; 131/134, PS 0/1; 258/7, stage IIIA/IIIB/IIIC; 37/197/31, colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year/5-year DFS rate was 76.0%(95%C.I. 70.3- 80.7)/70.6%(95%C.I. 64.7-75.7). The 3-year/5-year 0S rate was 95.8%(95%C.I. 92.5- 97.7)/88.1%(95%C.I. 83.5-91.5). ConclusionsIn Japanese patients with resected stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation. However, the 3-year DFS and 5-year OS rate in this trial were similar to several pivotal trials. Clinical trial identificationUMIN ID: 000004590. Legal entity responsible for the studyNon-Political Organization: Hokkaido Gastrointestinal Cancer Study Group. FundingNon-Political Organization: Hokkaido Gastrointestinal Cancer Study Group. DisclosureS. Yuki: Honoraria (self): Yakult Honsha Co. Ltd. All other authors have declared no conflicts of interest.

2702 Tumor Lysis Syndrome in a Patient With Gastric Adenocarcinoma

INTRODUCTION: Tumor lysis syndrome (TLS), considered a hematologic emergency, is uncommonly seen with solid tumors. TLS is most often seen in the context of aggressive lymphomas, where cell turnover is high. We present a case of tumor lysis syndrome in a patient with gastric adenocarcinoma, as a complication of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) chemotherapy. CASE DESCRIPTION/METHODS: 48-year-old male with metastatic gastric adenocarcinoma (Figure 1), who received his first cycle of FOLFOX 4 days prior, presented to the emergency department with slurred speech and altered mental status. Vitals at presentation were normal. Systemic examination was remarkable for agitation and disorientation to time, place and person. He had no focal neurologic deficits and rest of the exam was unremarkable. CT scan of the head and EEG were unrevealing. Laboratory analysis was significant for an elevated creatinine, phosphorus and uric acid (Table 1 day 5). The pattern of electrolyte abnormalities and their development after recent chemotherapy was consistent with a diagnosis of chemotherapy-induced laboratory and clinical TLS. Patient was managed with aggressive IV fluids and rasburicase, following which, the electrolyte abnormalities resolved, and he improved clinically back to baseline. DISCUSSION: Tumor lysis syndrome occurs when tumor cells release their contents into the bloodstream, either spontaneously or in response to therapy, leading to hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Complications include renal insufficiency, cardiac arrhythmias, seizures and death. Rapidly proliferating tumors like high-grade lymphomas and acute leukemias are predisposed to TLS. TLS occurs infrequently with solid tumors. TLS-associated mortality rate, with solid tumors, is around 35%; higher than that with hematologic malignancies. This is likely explained because prophylactic measures are implemented more often in hematological malignancies and less often in solid tumors. Our patient fulfilled the Cairo-Bishop criteria for grade II TLS. To our knowledge, there have been only nine cases of TLS secondary to gastric adenocarcinoma published in the literature. We present the first case of FOLFOX-induced TLS in a patient with gastric adenocarcinoma. This case highlights the importance of early recognition of TLS in patients with gastric cancer. Initiation of early treatment can reduce the high morbidity and mortality associated with this condition.

P-017 - Place of perioperative chemotherapy at the base of FOLFOX in the treatment of localized gastric cancers: a retrospective study of 31 cases

Introduction: The use of perioperative chemotherapy has significantly improved the prognosis of localized gastric cancer. Two studies validated this approach including one using Cisplatin despite the significant toxicity of this protocol. We conducted this study to evaluate the efficacy and toxicity of the FOLFOX protocol in this context. Methods: This retrospective study included patients followed for gastric cancer in the medical oncology department of the Mohammed V Military Training Hospital of Rabat in Morocco, for a period of 7 years, between 2011 and 2017. Patients received 4 cycles of FOLFOX as perioperative chemotherapy. The evaluation of the tumor response, after completion of the preoperative phase of chemotherapy, was performed by comparative computed tomography, tumor markers, and R0 surgery rates. Adverse events were classified according to the National Cancer Institute Common Toxicity Criteria version 4.0 classification. Results: This study included 31 patients. The use of preoperative chemotherapy showed a partial response in 14 patients (45.1%), stabilization of the disease in 15 patients (48.4%), while the tumor markers CEA and CA 19-9 were significantly decreased. The resection rate R0 was 83.87%. Hematologic grade ¾ toxicity was reported in only 2 patients (6.45%). Overall, 72.41% of patients benefited from scheduled postoperative chemotherapy. Conclusion: Our study is limited by its retrospective design and the small sample size, however, FOLFOX-based chemotherapy appears to be effective and well-tolerated in this setting and its place deserves to be analyzed in a larger study.

Clinical downstaging and quality of life after neoadjuvant chemotherapy in patients with locally advanced rectal cancer: Interim analysis from a phase II clinical trial.

e15178 Background: The role of neoadjuvant FOLFOX in achieving clinical downstaging and improvement in quality of life (QOL) in patients with locally advanced rectal cancer (LARC) remains to be established. We are conducting a phase II prospective clinical trial to evaluate the use of six cycles of FOLFOX as neoadjuvant chemotherapy in patients with T2-T3/N0-N+ rectal cancer. We now report tumor clinical downstaging and patient-reported QOL in our first patient cohort. Methods: Eleven Patients enrolled in our phase II prospective trial. Patients received three months of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) administered every two weeks. After three weeks of recovery, each patient was treated with conventional chemo-radiotherapy (5FU or capecitabine) All patients had an MRI and endorectal ultrasound at baseline and after completion of FOLFOX. A compilation of validated QOL questionnaires were also administered before and after FOLFOX. Results: A total of 11 patients completed the chemotherapy regimen. Based on pelvic MRI, complete clinical response (T0N0) was achieved by seven patients (64%), one patient (9%) was clinically downstaged but three (27%) didn’t have any changes following FOLFOX. Importantly, we found no disease progression during the FOLFOX course. QOL assessment after FOLFOX regimen showed trend towards improvement in general health, mobility, bladder control and psychological health. These changes in QOL were not statistically significant due to the small sample size. Patients self-grading of their general health before starting FOLFOX was 50% compared to 75% after. Of the five patients with pain at time of diagnosis, four reported complete pain relief while the fifth reported improvement from extreme to moderate pain. Three patients reported improvement in their anxiety/depression. In terms of bowel function, although there was trend towards improvement in the urgency subscale, other bowel functions subscales were unchanged. In general, scores for mobility, selfcare, and bladder function were slightly better after FOLFOX. Conclusions: This study suggests that adding only six cycles of neoadjuvant FOLFOX before CRT not only resulted in clinical downstaging of (LARC) but showed a trend toward improved QOL. This result provides some reassurance for oncologists that this approach does not diminish QOL with no risk of disease progression during the time of neoadjuvant chemotherapy. These findings need to be validated in a larger phase III trial.

Oxaliplatin and 5-fluorouracil (FOLFOX) in advanced well-differentiated digestive neuroendocrine tumors: A multicenter national retrospective study from the French Group of Endocrine Tumors (GTE).

4104 Background: Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs), however the available data are limited. Our aim was to assess the tumor response and survival in a large series of patients treated with oxaliplatin and 5-fluorouracil (FOLFOX) for advanced digestive NETs.Oxaliplatin-based regimens have shown promising antitumor activity in digestive neuroendocrine tumors (NETs), however the available data are limited. Our aim was to assess the tumor response and survival in a large series of patients treated with oxaliplatin and 5-fluorouracil (FOLFOX) for advanced digestive NETs. Methods: All patients with advanced well-differentiated digestive NETs treated with at least 3 cycles of FOLFOX between 2004 and 2018 in 12 centers of the French GTE, were retrospectively included. Best response according to the RECIST 1.1 criteria, progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors for PFS were investigated by multivariate analysis using a Cox proportional hazard model including variables with a p value ⩽ 0.20 in univariate analysis. Results: One hundred and forty-nine patients were included. Primary tumor location was pancreas (n = 88), small intestine (n = 37), stomach (n = 7), rectum (n = 4) and unknown without lung tumor at CT scan (n = 13). Partial response rate was of 31% for pancreatic NETs, 13% for small intestine NETs, 14% for gastric NETs, 25% for rectal NETs and 38% for unknown primary NETs. Median PFS were, respectively, 9, 9, 14, 4 and 6 months, and median OS were 30, 28, 31, 25 and 15 months. Significant poor prognostic factors for PFS after FOLFOX in digestive NETs were: progressive disease (HR = 2.5, p = 0.018), hepatic involvement &gt; 50% (HR = 1.8, p = 0.009), prior targeted therapy (HR = 1.5, p = 0.048) and rectal primary tumor (HR = 4.2, p = 0.01). Among pancreatic NETs, the 9 insulinomas had a 22 months PFS versus 9 months for the others (p = 0.025), and serum glucose normalization was obtained in 8 out of 9 cases. Conclusions: FOLFOX has a promising clinical activity for gastroenteropancreatic NETs, especially in insulinomas.

Clinical efficacy of Da Vinci robot-assisted radical resection for right colon cancer

Objective To investigate the clinical efficacy of Da Vinci robot-assisted radical resection for right colon cancer. Methods The retrospective cross-sectional study was conducted. The clinical data of 85 patients with right colon cancer who were admitted to the First Hospital Affiliated to Army Medical University from August 2013 to February 2019 were collected. There were 56 males and 29 females, aged from 29 to 84 years, with an average age of 60 years. All patients underwent Da Vinci robot-assisted radical resection of right colon cancer, named right hemicolon D3 + complete mesocolic excision, and received infection prevention and total parenteral nutrition treatment after surgery. According to clinical pathological staging of guideline issued by National Comprehensive Cancer Network, patients underwent postoperative chemotherapy within 1 year after surgery. Observation indicators: (1) treatment status; (2) postoperative pathological examination; (3) follow-up. Follow-up was conducted using outpatient examination, telephone interview and mail every 3 months within 1 year after surgery, every 6 months from 1 to 3 years after surgery, and once a year from 3 to 5 years after surgery up to March 2019. The postoperative tumor metastasis and survival of patients were obtained. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were described as M (range). Count data were expressed as absolute number. Survival rates were calculated using life-table method. Results (1) Treatment status: 85 patients underwent Da Vinci robot-assisted right hemicolon D3 + complete mesocolic excision successfully. The operation time, volume of intraoperative blood loss, time for postoperative out-of-bed activities, time to recovery of gastrointestinal function, time to liquid diet intake were (178±28)minutes, (85±33)mL, (2.9±1.8)days, (3.1± 2.7)days, (3.9±1.9)days, respectively. There was no perioperative death. Eleven patients had postoperative complications including 5 of anastomotic leakage, 2 of anastomotic bleeding, 2 of pulmonary infection, 1 of gastric emptying disorder and 1 of incomplete intestinal obstruction; they were cured and discharged after conservative treatment. All the 85 patients received postoperative infection prevention and total parenteral nutrition support, including 64 receiving systemic intravenous chemotherapy with 6-8 cycles of FOLFOX or XELOX, 7 receiving 6-8 cycles of oral capecitabine, and 14 receiving no chemotherapy. (2) Postoperative pathological examination: the number of harvested lymph nodes was 20±11 and 25 had lymph node metastasis. The length of proximal and distal cutting edge of the specimens was (16±5)cm and (9±5)cm, respectively. There was no cancerous cell on the cutting edge. High-differentiated adenocarcinoma, moderate-differentiated adenocarcinoma, moderate-differentiated tubular adenocarcinoma, low-differentiated adenocarcinoma, mucinous adenocarcinoma, tubular combined with mucinous adenocarcinoma were detected in 2, 40, 14, 16, 9, 4 patients, respectively. There were 8, 28, 24, 5, 12, 8 patients inⅠstage, ⅡA stage, ⅡB stage, ⅡC stage, ⅢB stage, ⅢC stage of TNM staging, respectively. (3) Follow-up: 85 patients were followed up for 1-67 months, with a median follow-up time of 19 months. During the follow-up, 1 of 85 patients had liver metastasis at 14 months after surgery and had survived after radiofrequency ablation treatment up to the end of follow-up. Three cases died of abdominal tumor metastases, 1 of which inⅡC stage died at 32 months after surgery, 1 in ⅢB stage died at 4 months after surgery and 1 in ⅢB stage died at 16 months after surgery. The 1-, 3-year overall survival rates were 97.1% and 94.0%, respectively. Conclusion Da Vinci robot-assisted radical resection of right colon cancer is safe and feasible, with good short- and long-term outcomes. Key words: Colon neoplasms; Right colon cancer; Right hemicolectomy; Da Vinci robotic surgical system; Prognosis

Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient mismatch repair (ATOMIC, Alliance A021502).

e15169 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (dMMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for cancers with proficient MMR. In an ongoing phase III randomized trial, we will determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR. By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that could serve as ‘immune priming'. Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR are randomized to modified FOLFOX6 for 6 months (12 cycles) alone (control arm) or combined with atezolizumab (840 mg IV q2 wk) with continuation of the antibody as monotherapy for an additional 6 months (total duration of 12 months) [experimental arm]. Patients will be stratified by T, N stage and tumor sidedness. Local testing for MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. One cycle of FOLFOX is allowed pre-registration. The targeted accrual goal of 700 patients and 165 disease-free survival (DFS) events will provide 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint of DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. Results: This study is being conducted by the Alliance for Clinical Trials in Oncology, was approved by NCI CTEP and activated in 09/2017. The study is actively accruing and, as of 02/11/2019, 152 patients are enrolled. We are actively exploring an international collaboration. Conclusions: This is a current clinical trial in progress. Clinical trial information: NCT02912559.

CLO19-023: Induction Chemotherapy Followed by Chemoradiation and Trans-Anal Full Thickness Local Excision or Total Mesorectal Resection in Patients With T2-T3/NO-N+ Adenocarcinoma of the Rectum; Preliminary Results of Phase 2 Prospective Clinical Trial

Background: The National Comprehensive Cancer Network (NCCN) Guidelines recently recognized total neoadjuvant therapy (TNT) as an acceptable option in patients with T3 and any N rectal cancer. Previous studies suggested that patients who received chemotherapy prior to conventional preoperative chemoradiation (CRT) and surgery allowed patients to receive more of their planned treatment with a better toxicity profile and increase in pathological response. However, those studies used a long course of FOLFOX or used capecitabine and oxaliplatin as an induction regimen. We are conducting a phase 2 prospective clinical trial to evaluate the use of 6 cycles of FOLFOX as TNT in patients with T2-T3/N0-N+. Patients and Methods: Patients with T2-T3/N0-N+ enrolled on our phase 2 prospective trial were included for this analysis. Patients received 6 cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), which was administered every 2 weeks. After 3 weeks of recovery period, patients then received conventional CRT with 5FU or capecitabine. All patients got MRI and endorectal ultrasound (ERUS) at baseline, after completing FOLFOX 3-months regimen and after finishing conventional CRT. Patients underwent either full-thickness local excision or total mesorectal resection depending on their tumor response to neoadjuvant therapy. The time interval between completion of radiation therapy and surgery ranged between 7and 12 weeks. Results: A total of 10 patients completed the chemotherapy and CRT treatment regimen. 9 patients proceeded to surgery and the 10th patient is scheduled for surgery. Clinical downstaging by MRI or ERUS was shown in 9 of 10 patients with only 6 cycles of FOLFOX. Complete clinical response was achieved in 6 patients as evident by ERUS/MRI of the pelvis after 3 months of FOLFOX before CRT. Complete pathological response was found in 4 of 9 patients (44%). In addition, 4 other patients had significant albeit not complete pathological response. Conclusions: This study suggests that adding only 6 cycles of neoadjuvant FOLFOX before CRT improved clinical and pathological downstaging of T2-T3/N0-N+ rectal adenocarcinoma and may facilitate organ preservation surgery. This is strategy needs to be investigated in larger phase III trials to validate these findings.

Fully laparoscopic resection of segment VII: tips and tricks

Background: Minimally invasive surgery can be challenging for hepatic lesions located in posterior-superior segments of the liver. Methods: We present a fully laparoscopic partial resection of segment VII for single metachronous metastasis of left colon adenocarcinoma. Results: A 57 years old man was diagnosed in 2014 with left colon adenocarcinoma treated by laparoscopic resection(pTNM:T3N0) MRI and PET CT performed in August 2016 showed a single 30 mm hepatic lesion in the segment VII consistent with metachronous metastasis. MDT decision was short course chemotherapy (4 cycles of FOLFOX) prior to surgery. In order to reassess the hepatic lesion,a new MRI scan was performed showing lesion stability and the patient underwent to a fully laparoscopic segment 7 resection. The patient was placed in a left lateral position.In total,we used 4 trocars(one 5 mm trocar and three 10 mm trocars). Intraoperative ultrasonography did not disclose additional lesions and the rest of abdominal exploration was normal. Partial resection of segment 7 was performed with CUSA,bipolar forceps and clips under intermittent Pringle maneuver(15 min with 5 min of release). An abdominal drain was left in place behind the right lobe of the liver. The patient was discharged at day 7 with an uneventful post-operative course. Pathology confirmed colorectal metastasis with 1.3cm margin. Four weeks after surgery,the chemotherapy was resumed. Conclusion: Safe laparoscopic liver resection in difficult segments requires specific patient position and port placement.

Fully laparoscopic resection of segment VII: tips and tricks

Background: Minimally invasive surgery can be challenging for hepatic lesions located in posterior-superior segments of the liver. Methods: We present a fully laparoscopic partial resection of segment VII for single metachronous metastasis of left colon adenocarcinoma. Results: A 57 years old man was diagnosed in 2014 with left colon adenocarcinoma treated by laparoscopic resection (pTNM:T3N0) MRI and PET CT performed in August 2016 showed a single 30 mm hepatic lesion in the segment VII consistent with metachronous metastasis. MDT decision was short course chemotherapy (4 cycles of FOLFOX) prior to surgery. In order to reassess the hepatic lesion, a new MRI scan was performed showing lesion stability and the patient underwent to a fully laparoscopic segment 7 resection. The patient was placed in a left lateral position. In total, we used 4 trocars (one 5 mm trocar and three 10 mm trocars). Intraoperative ultrasonography did not disclose additional lesions and the rest of abdominal exploration was normal. Partial resection of segment 7 was performed with CUSA, bipolar forceps and clips under intermittent Pringle maneuver (15 min with 5 min of release). An abdominal drain was left in place behind the right lobe of the liver. The patient was discharged at day 7 with an uneventful post-operative course. Pathology confirmed colorectal metastasis with 1.3cm margin. Four weeks after surgery, the chemotherapy was resumed. Conclusion: Safe laparoscopic liver resection in difficult segments requires specific patient position and port placement.