Purpose/Objective(s) Recent efforts aimed to add ICI to chemotherapy in the neoadjuvant and adjuvant setting (Neo/Adj) to improve outcomes of patients with resectable NSCLC. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of such strategy and identify subgroups of patients who may derive the most benefit. Materials/Methods Randomized control trials comparing Neo/Adj ICI plus chemotherapy vs chemotherapy alone in resectable NSCLC (pre-Sep 2022) were retrieved from PubMed, Embase, Cochrane Library and updated based on recent conferences. Primary outcomes were pathological complete response (pCR), event-free, disease-free, and progression-free survival (EFS, DFS, PFS). Secondary outcomes were major pathologic response (MPR), overall survival (OS), and safety. Subgroup analyses of EFS/ DFS/ PFS included histology, smoking status, and PDL-1 status. Pooled hazard ratios (HR), odds ratios (OR) and risk ratios (RR) were meta-analyzed using the generic variance, Peto and Mantel-Haenszel methods as appropriate. Random effect models were used to compute pooled estimates. Results 3926 patients across five neoadjuvant and two adjuvant trials were included. Neoadjuvant ICI improved pCR fivefold compared to chemotherapy alone (OR 5.35; 95% CI, 4.02 - 7.13). Both neo- and adjuvant use of ICI decreased recurrence risk by 34% (HR 0.66; 95% CI, 0.54 - 0.81). Two-year OS improved with adding either neo- or adjuvant ICI (RR 0.73; 95% CI, 0.58 - 0.92) with a trend towards better median OS (HR 0.76; 95% CI, 0.57 - 1.02). Neoadjuvant ICI improved MPR fourfold vs. chemotherapy (OR = 3.91; 95%, CI 2.90 - 5.28). In subgroup analyses, those with non-squamous NSCLC, ever smokers, and tumors with PD-L1>=1% seem to derive a greater benefit from ICI. Neo/Adj ICI increased immune-related adverse effects risk threefold (RR = 3.36; 95% CI, 2.11 - 5.36), with an increase in grade 3 treatment-related toxicity (RR = 1.28; 95% CI, 0.93 - 1.78). Conclusion Based on preliminary data, adding Neo/Adj ICI improves recurrence rate in resectable NSCLC with a trend towards improved OS. Safety signals were consistent with historical data. Further subgroup evaluations may help to identify suitable population for either approach.

Introduction: This case report outlines a 70-year-old female patient who presented with a concurrent mixed AIHA and a gastric adenocarcinoma. Case presentation: Her treatment course of these two diseases are summarized, which included supportive care, neoadjuvant chemotherapy for her gastric adenocarcinoma, steroids, rituximab, and surgical resection of the tumor. This approach ultimately led to the stabilization of her AIHA and primary cure for her solid malignancy. Conclusion: We briefly review both AIHA and gastric adenocarcinoma as clinical entities, propose working causes of hemolytic anemia including gastric adenocarcinoma, and outline a successful treatment pathway for these two concurrent conditions.

The FLAURA study established osimertinib as a preferred first-line standard of care for patients with the two ‘common’ types of epidermal growth factor receptor mutation-positive (EGFR+) advanced non-small-cell lung cancer (aNSCLC). Second-line (2L) treatment is typically platinum pemetrexed chemotherapy and the standard third-line (3L) treatment is docetaxel, which has a modest response rate of 7 - 15%. Previously, when first generation (1G) EGFR tyrosine kinase inhibitors (TKIs) were standard of care in the first-line setting, a number of prospective and retrospective studies examined 3L rechallenge with the same 1G EGFR TKI following 2L chemotherapy, with varying levels of success.

In lung cancer, previous studies have explored the utility of conventional tumor biomarkers as surrogates for radiographic staging to improve diagnosis, prognosis, and augment treatment decisions. However, to date most have been performed in the context of a particular therapeutic regimen or prognostic variable. As such, the purpose of this study was to assess whether or not three commonly available, low-cost serum biomarkers (CEA, CA19-9, and CA-125) associated with radiographic disease response/progression during or after the treatment of non-small cell lung cancer (NSCLC).

Among patients(pts) with resectable Non-Small-Cell-Lung-Cancer(NSCLC), survival outcomes, despite standard of care adjuvant therapies, remains suboptimal. Pts with advanced KRAS mutated(KRASm) tumors benefit from molecularly-directed KRAS inhibitors. Efforts to improve outcomes using molecularly-targeted therapies are underway in the early-stage setting. The objective of this study was to evaluate the prevalence/distribution and outcomes of pts with resected(stage I- III) KRASm NSCLC in the real world setting in Southwestern Ontario.

Presenter: Evelyn Waugh MD | London Health Sciences Centre Background: Patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) are at elevated risk of systemic disease at diagnosis. Neoadjuvant chemotherapy (NAC) may address systemic and downstage locoregional disease prior to surgical resection. This study examines the effects of NAC in patients with borderline resectable PDAC in comparison to those who underwent upfront pancreaticoduodenectomy. Methods: The AHPBA criteria for borderline resectability and/or a CA19-9 value >100 defined borderline resectable tumours retrieved from an institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. Secondary outcomes included margin status, stage, recurrence, length of stay (LOS) and 30-day morbidity. Chemotherapy response was assessed in the subset receiving NAC. Data were reported using descriptive statistics and comparisons between groups using students t-tests, Mann Whitney-U tests, and chi-square tests as appropriate. Survival analyses were conducted using Kaplan-Meier and Cox Proportional Hazard models based on intention to treat. Results: 87 patients with borderline resectable PDAC were identified. 40 underwent NAC and 46 underwent upfront surgery. The groups had similar mean age (65.9 vs. 64.7), gender and preoperative comorbidities. Median pre-treatment CA19-9 corrected for bilirubin was lower in the NAC group (10.6 vs. 125, p = 0.03). 70% (28) of patients undergoing NAC proceeded to surgery. Of the operative patients, 85.7% (24) of the NAC group and 62% (28) of the upfront surgery group were resectable. 1 year OS was 70% (28) in the neoadjuvant group and 39% (18) in the upfront surgery group (p < 0.01). 3 year OS was 43% (17) in the neoadjuvant group and 4.3% (2) in the upfront surgery group (p <0.001). Median OS was 12.6 months in the NAC group and 10 months with upfront surgery. Median follow-up was 337.5 days (range = 31 – 2314). In the operative NAC group, median survival was 20 months, 1 year OS was 85% and 3 year OS was 21%. Both had comparable median time to recurrence (276.5 vs. 260.5 days, p = 0.61), LOS (10 days vs. 11 days, p = 0.11) and 30-day morbidity (35.7% vs. 35.6%, p = 0.36). The NAC group had lower rates of positive margins (8.3% vs. 32.1% p = 0.04) and lymph node metastasis (44% vs. 65.6%, p = 0.1). In operative NAC patients, 57.1% had a decrease in CA19-9, 65.5% had a decrease in tumour size on re-staging imaging and 56% had a pathological response in their surgical specimens. Conclusion: This analysis indicates an OS benefit for patients with borderline resectable PDAC undergoing NAC. Patients undergoing NAC had an improved resection rate, R0 margins and lymph node status compared to upfront surgery.

# 01. Design and validation of a unique endoscopy simulator using a commercial video game {#article-title-2} Procedural simulation has been shown to enhance early endoscopy training. In this proof of concept study, we aimed to show that a first-person shooter (FPS) video game with a novel in-house

Background: Prognosis of resectable pancreatic adenocarcinoma improves with the use of adjuvant chemotherapy with 5-year survival rate approaching 21% following a complete course. Despite these promising Results, many patients who undergo resection do not complete the planned adjuvant regimen. The benefit from partial treatment is largely unknown. Understanding what factors lead to reduced chemotherapy completion rates and its impact on patient outcomes will help to guide management decisions in this patient population. Methods: A cohort analysis was performed using a clinical database from a tertiary referral hospital and included patients undergoing pancreatic resection for ductal adenocarcinoma from 2007 to 2016. Patients who completed planned adjuvant chemotherapy were compared to those who did not. Overall survival and disease free survival using a Cox proportional hazards model adjusting for confounding variables was used. A logistic regression analysis was performed to evaluate what factors may influence adjuvant chemotherapy completion rates following resection. Results: The study cohort included a total of 98 patients with 54 completing chemotherapy and 44 who did not. Disease free survival at 1-year was significantly improved with completing chemotherapy (HR 0.225, p < 0.01). However, this effect was no longer seen when overall disease free survival was evaluated (HR 0.901, p = 0.76). There were no measurable differences in 1-year (HR 0.997, p = 0.99) or overall survival (HR 0.993, p = 0.98) between these groups. Chemotherapy completion rates were reduced with increasing age (p < 0.01) and improved with the addition of adjuvant radiation (p < 0.01). Peri-operative complications, pancreatic fistula, length of stay, and time from resection to first chemotherapy treatment did not have a significant impact on chemotherapy completion rates. Sub-group analysis showed in patients who received adjuvant radiation, completion of chemotherapy was associated with a significantly reduced 1-year disease free survival (HR 0.100, p < 0.01). This relationship was not seen in patients who did not receive radiation (HR 0.35, p = 0.11). Conclusion: Completion of adjuvant chemotherapy in patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma appears to have a disease-free survival benefit within the first year, but its effect is lost beyond this point. Despite incomplete treatment, overall and 1-year survival did not appear to be adversely affected. These Results suggest that complete and partial adjuvant chemotherapy have similar long-term benefits. Patients who received radiation therapy had a higher rate of completion of their planned chemotherapy regimen, possibly secondary to the break from the chemotherapy agents while receiving radiation.

Objectives: No overall survival (OS) benefit has been reported from a mature randomized trial with the use of ALK inhibitors. We conducted a systematic review and meta-analysis to assess the efficacy of ALK inhibitors compared to chemotherapy (ALK vs. chemo) and 2nd generation ALK inhibitors compared to 1 st generation ALK inhibitors (ALK-2 G vs. ALK-1 G). Methods: The electronic databases Medline (PubMed), EMBASE, and the Cochrane Database of Systematic Reviews were searched for relevant randomized trials. Pooled hazard ratios (HR) for OS and progression free survival (PFS), and pooled risk ratios for objective response rates (ORR) and toxicity were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. To account for between-studies heterogeneity, random-effect models were used. Subgroup analyses compared PFS by gender, smoking status, brain metastases, race and age. Results: Six trials were included in the analysis of ALK vs. chemo and four in the analysis of ALK-2 G vs. ALK-1 G. Treatment with ALK inhibitors improved OS compared to chemotherapy (HR: 0.84, 95 %CI 0.72-0.97) while a trend toward a better OS was seen with ALK-2 G vs. ALK-1 G (HR: 0.66, 95 %CI 0.43-1.02). PFS was improved with ALK vs. chemo and ALK-2 G vs. ALK-1 G (HR: 0.44, 95 %CI 0.35-0.54 and HR: 0.38, 95 %CI-0.29-0.51, respectively). ORR was improved with ALK vs. chemo and ALK-2 G vs. ALK-1 G. No difference in toxicity was observed. Conclusions: This meta-analysis is the first, to our knowledge, to report an OS and PFS benefit with the use of ALK inhibitors compared to chemotherapy from randomized trial data. A trend toward a better OS was also seen with ALK-2 G vs. ALK-1 G and this is likely because of crossover effects and limited OS follow-up. Longer follow up and further research are warranted to directly compare ALK inhibitor sequences and to understand the outcomes of second generation ALK inhibitors as initial therapy.

MATE1 (multidrug and toxin extrusion protein 1/SLC47A1) has an important role in the renal and biliary excretion of endogenous and exogenous organic cations including a number of therapeutic drugs. We recently reported that homozygosity for a single nucleotide polymorphism in MATE1 (rs2289669) (A/A) was independently protective for cisplatin-related ototoxicity in patients with head and neck squamous cell carcinoma (HNSCC) receiving cisplatin-based chemoradiation. To evaluate whether MATE1 A/A status had any effect on treatment efficacy we examined cancer outcomes in a subset of our patients expected to have a poorer prognosis.

Platinum doublet chemotherapy is generally the backbone treatment of advanced NSCLC (aNSCLC), although toxicity and limited benefit necessitated the need for investigation of alternatives. We examined vinorelbine and ifosfamide combination chemotherapy as a possible alternative in first-line aNSCLC. 31 patients were enrolled and treated between January 2004 and July 2006. Vinorelbine (25 mg/m2) and escalating doses of ifosfamide were given on days 1 and 8 q21 days. The starting dose of ifosfamide was 2.0 g/m2. If ≤1/6 patients experienced dose-limiting toxicities (DLT) in cycle 1, the next cohort was recruited and given an additional 0.25 g/m2 of ifosfamide. If ³ 2/6 patients within a cohort experienced DLT, recruitment was halted, and previous cohort's dose was determined to be ideal for phase II study. DLT were defined as grade 4 hematologic or grades 3 or 4 non-hematologic toxicities. The ideal phase II ifosfamide dose was determined to be 2.0 g/m2. Median PFS and OS were 5.5 and 9.2 months, respectively. The ORR was 12.9% and the 1-year OS was 21%, both lower than historical reports of platinum doublet efficacy and even vinorelbine monotherapy at 30 mg/m2. Six "excellent responders" were identified who survived between 20 and 45 months. DLT were experienced by 58% of patients. DLT were largely hematologic, but higher doses of ifosfamide produced non-hematologic toxicities. There was no significant evidence that vinorelbine and ifosfamide combination could provide an alternative to platinum doublet chemotherapy based on inferior efficacy and the high rate of DLT. The 6 "excellent responders" may be explained by chance or secondary to subsequent treatment with erlotinib while harbouring occult EGFR mutations. Further study may be relevant to examine synergy between vinorelbine or ifosfamide with modern targeted therapies.

BACKGROUNDCombination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial.METHODSA multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1-14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity.RESULTSMedian age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0-50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh).CONCLUSIONSToxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.