Borderline Resectable Disease Research Articles

Risk of hepatic steatosis with the preoperative treatment of pancreatic cancer and the short-term postoperative outcomes.

We investigated whether the preoperative treatment of patients with pancreatic cancer is a risk factor for hepatic steatosis (HS), and whether preoperative HS affects the short-term postoperative outcomes. Patients who underwent radical surgery for pancreatic cancer between 2010 and 2023 were enrolled. The patients' medical records were reviewed. Albumin and carbohydrate antigen 19-9 were measured before and after chemotherapy in the patients who received preoperative chemotherapy. A logistic regression univariate analysis was performed to analyze the factors associated with new-onset HS. A total of 230 patients who underwent surgery were included. HS was observed on the date of surgery in 11 (10%) and two (2%) patients with and without preoperative chemotherapy, respectively. Female sex, initially borderline resectable or unresectable disease, history of cholangitis, presence of PEI, long-term (≥ 3months) biliary drainage, preoperative chemotherapy, and serum albumin ≥ 3.9mg/dl before chemotherapy were identified as risk factors for HS. The incidence of postoperative morbidity did not differ between the patients with and without preoperative steatosis. Preoperative chemotherapy, a history of cholangitis, the presence of PEI, and ≥ 3months' duration of biliary drainage were risk factors for the development of HS before surgery for pancreatic cancer. However, preoperative HS did not affect the short-term postoperative outcomes.

Molecular and clinical features of pancreatic acinar cell carcinoma: A single institutional experience.

e16335 Background: Acinar Cell Carcinoma (ACC) accounts for around 1% of pancreatic cancer. The molecular and clinical features of acinar cell carcinoma are less characterized. We sought to evaluate the clinical and molecular features of patients with ACC at MD Anderson Cancer Center. Methods: Patients with ACC who had germline and/or somatic molecular testing at MD Anderson Cancer Center from 2008 to 2022 were identified retrospectively. After obtaining approval of approval of the institutional review board genomic alterations including germline or somatic BRCA mutations, KRAS mutation, demographic, clinical, and pathological information were extracted from institutional databases using the Palantir Foundry software platform (Syntropy); this included natural language processing with subsequent validation by manual chart review. Overall Survival (OS) was calculated from the date of diagnosis to death or last follow-up. The Kaplan-Meier method was used for survival analysis. Results: 16 patients were identified with molecular testing results available. There were 13 males and 3 females. The median age of diagnosis was 62.5 years (range 49 -72). 14/16 patients (87.5%) had metastatic disease, one (6.25%) patient had borderline resectable disease and one (6.25%) had localized resectable disease at initial diagnosis. Median OS was for 24 months for patients with metastatic disease. There were 2 patients with mixed pathology, 1 with acinar cell carcinoma with neuroendocrine features and the 2nd had mixed acinar cell-ductal carcinoma. 15/16 (93.75%) patients were tested for KRAS and all 15 were KRAS wildtype. Somatic mutations in DNA damage repair genes (BRCA2, PALB2) were present in 3 patients (25%) and 2 patients had germline mutation (BRCA and ATM) (16%) out of 12 patients tested for those genes. 6/16 (37.5%) patients were treated with FOLFIRINOX at first line. 3/6 (50%) of these patients had partial response, 2/6 (33%) had stable disease and only 1/6 (16%) had progression. 5 patients were treated with FOLFOX based regimen and 1/5 (20%) had response, 2/5 (40%) had stable disease and 2/5 (40%) had progression of disease. 5 patients were treated with gemcitabine-based regimen and only 1 had response which received gemcitabine/nab-paclitaxel combined with cisplatin. Conclusions: ACC were KRAS wild type and had higher rates of germline/somatic mutations in DNA damage repair genes. Better treatment outcome of FOLFIRNIOX/ platinum-based regimens was suggested based on this limited patient dataset. Larger studies are needed to further understand the molecular features of ACC and guide the treatment of this rare entity of pancreatic cancer.

Reconsideration of the clinical impact of neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: A dual-institution collaborative clinical study

PurposeWe investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. MethodsA total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. ResultsIn resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. ConclusionsNAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

Management of Intrahepatic Cholangiocarcinoma: A Narrative Review.

The management of resectable intrahepatic cholangiocarcinoma remains a challenge due to the high risk of recurrence. Numerous clinical trials have identified effective systemic therapies for advanced biliary tract cancer; however, fewer trials have evaluated systemic therapies in the perioperative period. The objective of this review is to summarize the current recommendations regarding the diagnosis, surgical resection, and systemic therapy for anatomically resectable intrahepatic cholangiocarcinoma. Our review demonstrates that surgical resection with microscopic negative margins and lymphadenectomy remains the cornerstone of treatment. High-level evidence regarding specific systemic therapies for use in resectable intrahepatic cholangiocarcinoma remains sparse, as most of the evidence is extrapolated from trials involving heterogeneous tumor populations. Targeted therapies are an evolving practice for intrahepatic cholangiocarcinoma with most evidence coming from phase II trials. Future research is required to evaluate the use of neoadjuvant therapy for patients with resectable and borderline resectable disease.

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.

Resection to Exploration Ratios and Associated Outcomes in Patients with Pancreatic Ductal Adenocarcinoma.

To investigate resection/exploration ratios (RER), reasons for omission of pancreatectomy, and survival outcomes in patients undergoing surgical exploration with resection intent for pancreatic ductal adenocarcinoma (PDAC). While surgical indications for PDAC are expanding, information about intraoperative attrition is lacking. The RER was calculated in PDAC patients undergoing exploration from 2018 through 2020. Factors associated with uncompleted resection and survival were identified using multivariable models. In total, 681 patients were included. Upfront explorations were 296 (43.7%), and post-neoadjuvant explorations were 385 (56.3%). The overall RER was 89.7% (90.5% in the upfront setting and 89.1% post-neoadjuvant treatment). In this latter subgroup, the RER decreased from 96.1% in resectable disease to 86.6% in borderline resectable disease and 61.9% in locally advanced disease. The primary reasons for uncompleted resection were occult metastases in presumed resectable/borderline resectable disease (without difference between upfront and post-neoadjuvant operations) and local unresectability in locally advanced disease. No preoperative variable was associated with uncompleted resection in upfront explorations, while anatomical staging informed the likelihood of surgical attrition following neoadjuvant treatment. Uncompleted resection was invariably associated with a median survival of around one year. The median post-pancreatectomy survival was 36.9 months in the upfront setting and 29.5 months following neoadjuvant treatment. The median survival from diagnosis in patients receiving post-neoadjuvant resection was 34.5 months. This analysis provided contemporary information about resection rates, reasons for intraoperative attrition, and survival outcomes in the entire spectrum of PDAC patients selected for surgical exploration at an experienced institution.

Oncological role of surgical resection in patients with pancreatic ductal adenocarcinoma with liver-only synchronous metastases in a single-center retrospective study.

Surgical resection for liver-only synchronous metastases of pancreatic ductal adenocarcinoma remains controversial. We investigated the role of conversion surgery in patients with a favorable response to systemic chemotherapy. Patients (n=49) were diagnosed liver-only synchronous metastases using staging laparoscopy or open laparotomy between 2007 and 2022. Clinical outcomes were retrospectively compared among patients who underwent conversion surgery (n=10), upfront surgery with or without short-term neoadjuvant chemotherapy (UpS/short NAC) for oligometastases and occult metastases limited to the liver (n=8), and chemotherapy only for resectable or borderline resectable disease with occult liver-only metastases (n=31). The surgical indication of conversion surgery was fixed as the ABC criteria, namely, Anatomical objective response of disappearance of liver metastases on imaging studies, Biological response of CA19-9 level decrease to ≤150 U/mL, and Conditional response of surgical fitness. In addition to the above ABC criteria, tumor disappearance at the liver was repeatedly confirmed using staging laparoscopy (laparoscopic response; L), and metabolic complete responses were confirmed using positron emission tomography-computed tomography (CT) (metabolic response; M). Median survival time from initial treatment was 9.9 months [95% confidence interval (CI): 8.3-10.9] in the chemotherapy group, 10.4 months (95% CI: 6.6-17.8) in the UpS/short NAC group, and 36.7 months (95% CI: 19.0-84.8) in the conversion surgery group (conversion surgery vs. UpS/short NAC, P=0.002; conversion surgery vs. chemotherapy, P<0.001; UpS/short NAC vs. chemotherapy, P=0.554). One patient in the UpS/short NAC group and three in the conversion surgery group achieved 5-year survival. Among them, two patients with initially multiple liver metastases (≥10) in the conversion surgery group survived beyond 5 years. Only conversion surgery was a significant independent prognostic factor in a total cohort (hazard ratio; 0.173, P=0.002). Conversion surgery, but not UpS/short NAC, may enhance survival in patients with synchronous liver metastases and favorably anatomical, biological and conditional responses to systemic chemotherapy.

A O03 Host phenotypic adversity independently predicts progression to resection in neoadjuvantly-treated pancreatic cancer

Abstract Background Neoadjuvant treatment (NAT) offers a modest survival benefit to the otherwise dismal outcomes of pancreatic ductal adenocarcinoma (PDAC), however methods for assessing treatment response and disease trajectory during NAT are limited. Cachexia and sarcopenia are hallmark features of PDAC and defining host phenotypic adversity is crucial in understanding the tumour-host relationship and its influence on clinical outcomes. We sought to determine the relationship between body composition, systemic inflammation, and outcomes in NAT PDAC to lay foundations for improving assessment of treatment response. Methods This is a retrospective, observational study with an intention-to-treat design, analysing resected (n = 109) and non-resected (n = 117) NAT PDAC (total n = 226) from the tertiary West of Scotland Pancreatic Unit, Glasgow Royal Infirmary. Patients were included if they had resectable or borderline resectable disease and received NAT. Patients were excluded if they had locally advanced or metastatic disease. Body composition was determined by single-slice L3 cross-sectional measurements. Results Patients with an adverse phenotype defined by change in body composition were less likely to progress to resection (40.9% vs 68.8%, p &amp;lt; 0.001). Logistic regression confirms the independence of this effect (OR 3.79, 95% CI 1.99-7.22, p &amp;lt; 0.001). There was a trend towards systemic inflammation in the non-resected group (CRP rise 51.4% vs 29.9%, p = 0.008). Patients treated with Folfirinox who required dose reduction received higher doses of irinotecan, 5-fluorouracil (bolus) and 5-fluorouracil (infusion) per unit muscle mass (7.3 vs 6.9mg/cm2⋅m-2, p = 0.010; 16.2 vs 14.7mg/cm2⋅m-2, p = 0.002; 96.5 vs 91.1mg/cm2⋅m-2, p = 0.026). Conclusions Host phenotypic adversity during NAT presents a potentially valuable addition to a limited arsenal of tools to aid decision making in resectable and borderline resectable PDAC. Early assessment of body composition trend during chemotherapy may present an opportunity to switch the host phenotype from adverse to favourable in some patients, or highlight the futility of continuing aggressive treatment in others. Chemotherapeutic prescribing by body surface area overlooks crucial differences in lean body mass and may be exposing patients to avoidable and burdensome toxicities.

Endoscopic Ultrasound-Guided Fiducial Placement for Stereotactic Body Radiation Therapy in Patients with Pancreatic Cancer.

Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. Most patients included in the study had either locally advanced disease (32 patients, 39%) or borderline resectable disease (29 patients, 35%). Eighty-two PC patients underwent the placement of 230 fiducial markers under EUS guidance. The technical success rate of the fiducial placement was 98%. No immediate EUS-related adverse events were reported. The average time to the simulation CT after fiducial placement was 3.1 days. Of the 216 fiducial markers used for the SBRT delivery, 202 fiducial markers were visible on both the simulation CT and the cone beam CT scan. A median dose of 40cGY was given to all the patients in five fractions. Of these, 41% of the patients reported no SBRT-related toxicities during the follow-up. Fatigue and nausea were the most reported SBRT-related toxicities, which were seen in 35% of the patients post-SBRT. Our results demonstrate that EUS-guided fiducial placement is safe and effective in target volume delineation, facilitating SBRT delivery in PC patients. Further clinical trials are needed to determine the SBRT-related survival benefits in patients with pancreatic cancer.

Financial toxicity in patients with newly diagnosed pancreatic cancer: A prospective cohort study.

29 Background: Financial toxicity (FT) refers to the financial strain and distress experienced by patients due to the costs associated with cancer care. Patients with pancreatic ductal adenocarcinoma (PDA) experience unique challenges including limited treatment options, aggressive disease progression, complex multidisciplinary care needs and an overall limited prognosis. The aim of this preliminary analysis was to measure FT in patients newly diagnosed with PDA and determine factors associated FT. Methods: In this prospective cohort study, patients with newly diagnosed PDA prior to treatment initiation were enrolled through a pancreatic multi-disciplinary clinic at a single institution. The Comprehensive Score for Financial Toxicity (COST), a validated instrument for measuring FT, was used to measure participant’s baseline FT upon initial clinic visit and at two-month intervals via online survey. Mean baseline COST scores were compared using a two-sided t test for binary variables and an ANOVA test for categorical variables with &gt;2 categories. Demographic information including age, race, educational experience, income and insurance status was also collected by questionnaire. Results: Between July 2021 and March 2023, 63 patients were enrolled of which 45 participants completed the baseline surveys (71% response rate). Patients with higher stage disease experienced higher baseline financial toxicity, with mean COST score 38.0 for resectable disease, 26.9 for borderline resectable disease, 22.1 for unresectable disease and 17.5 for metastatic disease (p = 0.03). Participants enrolled in Medicaid experienced the highest FT (mean COST 16.0), while those enrolled in Medicare reported the lowest FT (mean COST 31.8). Participants having private insurance fell in-between with a mean COST score 22.1. Baseline FT also varied inversely with household income with participants with annual household incomes &lt;$50,000 experiencing the most FT (mean COST = 12.7) and participants with annual household incomes &gt;$200,000 experiencing the least FT (mean COST = 34.6). Conclusions: Patients with more advanced pancreatic cancer not only face a worse prognosis but also experience heightened financial strain even before initiation of therapy, emphasizing the early vulnerability of these individuals both medically and financially. Future analyses will measure FT longitudinally after treatment initiation and measure the association between FT, response to therapy and mortality. [Table: see text]

Definitive Radiotherapy for the Treatment of Gross Disease in Unresected Differentiated Thyroid Cancer

While surgery (with or without radioactive iodine (RAI)) is the mainstay of locoregional control in differentiated thyroid cancer (DTC), patients with unresectable disease present a clinical challenge. Uncontrolled disease in the neck can lead to substantial morbidity and mortality in DTC and obtaining locoregional control is vital to preserving quality of life and longevity. High dose definitive radiotherapy (RT) for gross disease in DTC is understudied. This study examines the efficacy of definitive RT in this setting. From an IRB-approved registry of head and neck cancer cases treated at a tertiary care center over a period of 8 years (2014-2022), patients with incompletely resected or unresectable DTC including papillary, follicular, mixed, medullary, and poorly differentiated types were identified. All patients were treated to the neck and/or thyroid regions with visible gross disease to a definitive dose of radiation. The primary endpoint was local control within the radiated portal with a secondary endpoint of locoregional control within the neck. A total of 31 patients were identified, of whom 74.2% were Caucasian. Fourteen were female (45.2%), and 17 (54.8%) were male. The median age was 68 years (range 26-90) and the median follow-up was 31 months. Histologically, 19 (61.3%) cases were papillary, 4 (12.9%) were follicular, 2 (6.5%) were mixed, 3 (9.7%) were medullary, and 3 (9.7%) were poorly differentiated. Among patients with non-medullary DTC 18 (69.2%) received prior RAI. Twelve patients were treated with radiation at initial diagnosis, while 19 patients were treated at the time of recurrence; two patients received concurrent chemotherapy. Twenty-eight patients (90.3%) were treated with IMRT and 3 (9.7%) were treated with SBRT. The median dose to the gross disease was 66 Gy (range 30-70.4) in 32 fractions (range 5-35). Overall, 5 patients (16.1%) experienced a locoregional failure after RT and all experienced failure in the RT portal. The actuarial infield control/locoregional control of radiation therapy at 3 and 5 years was 84.8% and 74.2%, respectively. Overall survival at 3 and 5 years was 68.5% and 47.4%, respectively. Among patients who had a locoregional failure after RT, 2 patients were salvaged with systemic therapy, 2 patients with surgery, and 1 patient with SBRT re-irradiation (40 Gy/5 fractions). The patient salvaged with SBRT remains without disease 8 months post-RT. Definitive radiotherapy is a highly effective strategy to obtain durable control of unresected DTC. It should be standard for unresected disease and considered as a viable alternative for patients with borderline resectable disease for whom resection would be highly morbid.

The role of diagnostic, prognostic, and predictive biomarkers in the management of early pancreatic cancer.

Despite modern advances in cancer medicine, pancreatic cancer survival remains unchanged at just 12%. For the small proportion of patients diagnosed with 'early' (upfront or borderline resectable) disease, recurrences are common, and many recur soon after surgery. Whilst chemotherapy has been shown to increase survival in this cohort, the morbidity of surgery renders many candidates unsuitable for adjuvant treatment. Due to this, and the success of upfront chemotherapy in the advanced setting, use of neoadjuvant chemotherapy has been introduced in patients with upfront or borderline resectable disease. Randomized controlled trials have been conducted to compare upfront surgery to neoadjuvant chemotherapy in this patient cohort, opinions on the ideal upfront treatment approach are divided. This lack of consensus has highlighted the need for biomarkers to assist in clinical decision making. This review analyses the potential diagnostic, prognostic and predictive biomarkers that may assist in the diagnosis and management of early (upfront and borderline resectable) pancreatic cancer.

High-resolution pancreatic computed tomography for assessing pancreatic ductal adenocarcinoma resectability: a multicenter prospective study.

This prospective multicenter study aimed to evaluate the diagnostic performance of 80-kVp thin-section pancreatic CT in determining pancreatic ductal adenocarcinoma (PDAC) resectability according to the recent National Comprehensive Cancer Network (NCCN) guidelines. We prospectively enrolled surgical resection candidates for PDAC from six tertiary referral hospitals (study identifier: NCT03895177). All participants underwent pancreatic CT using 80 kVp tube voltage with 1-mm reconstruction interval. The local resectability was prospectively evaluated using NCCN guidelines at each center and classified into three categories: resectable, borderline resectable, and unresectable. A total of 138 patients were enrolled; among them, 60 patients underwent neoadjuvant therapy. R0 resection was achieved in 103 patients (74.6%). The R0 resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable disease, respectively, in 78 patients who underwent upfront surgery. Meanwhile, the rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively, in patients who received neoadjuvant therapy. The area under curve of high-resolution CT in predicting R0 resection was 0.784, with sensitivity, specificity, and accuracy of 87.4% (90/103), 48.6% (17/35), and 77.5% (107/138), respectively. Tumor response was significantly associated with the R0 resection after neoadjuvant therapy (odds ratio [OR] = 38.99, p = 0.016). An 80-kVp thin-section pancreatic CT has excellent diagnostic performance in assessing PDAC resectability, enabling R0 resection rates of 88.7% and 90.9% for patients with resectable PDAC who underwent upfront surgery and patients with resectable PDAC after neoadjuvant therapy, respectively. • The margin-negative (R0) resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable pancreatic ductal adenocarcinoma (PDAC), respectively, on 80-kVp thin-section pancreatic CT in the 78 patients who underwent upfront surgery. • Among the 60 patients who underwent neoadjuvant therapy, the R0 rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively. • Tumor response, along with the resectability status on pancreatic CT, was significantly associated with the R0 resection rate after neoadjuvant therapy.

Multimodality liver directed treatment for colorectal liver metastasis: Array of complementary options can improve outcomes -A single centre experience from India.

Complimentary use of Liver directed therapies (LDTs) with systemic chemotherapy has improved oncologic outcomes in colorectal liver metastasis (CRLM). We analysed institutional results of multimodality management. Retrospective analysis of prospectively maintained database of CRLM patients managed with LDT including surgical resection, Ablation, Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE) between November 2011 to March 2020. Management plan was decided in multidisciplinary meeting. Resectable tumours underwent surgical resection or ablation or both in some cases. Borderline resectable or unresectable disease was treated with down staging chemotherapy or TACE/TARE followed by resection or ablation. All patients received adjuvant chemotherapy. Factors influencing survival were analysed. Out of total 375 patients, surgery alone was done in 191 (50.93%) patients while surgery with other LDT in 26 patients (6.93%). Ablation alone was done in 100 (26.66%) whereas TACE/TARE were done as standalone treatment in 21 (5.6%) and 7 (1.86%) patients respectively. TACE + ablation was done in 28 (7.46%) and TARE + ablation was done in 2(0.53%) patients.5-year Overall Survival(OS) was 49.8% while Event free survival(EFS) was 21.4%. The median OS and EFS for surgical group was significantly better than non-surgical group (78 V/s 39 months; p<0.05 and 20 V/s 15 months p <0.005). The resectable (78 months) group had better median OS as compared to borderline resectable and Unresectable group (39 months and 29 months). Male gender, resectable disease and surgical intervention were associated with improved OS. Although surgery remains the mainstay of treatment, complementary use of non-surgical LDT with systemic therapy offers possibility of good outcomes in advanced liver limited disease. Our experience highlights the impact of multidisciplinary care in optimizing CRLM treatment.

Neoadjuvant therapy for pancreatic cancer.

Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with surgical resection of the primary tumour and systemic chemotherapy, which provides considerably longer overall survival (OS) durations than either modality alone. Regardless, most patients will have disease relapse owing to micrometastatic disease. Although currently a matter of some debate, considerable research interest has been focused on the role of neoadjuvant therapy for all forms of resectable PDAC. Whilst adjuvant combination chemotherapy remains the standard of care for patients with resectable PDAC, neoadjuvant chemotherapy seems to improve OS without necessarily increasing the resection rate in those with borderline-resectable disease. Furthermore, around 20% of patients with unresectable non-metastatic PDAC might undergo resection following 4-6 months of induction combination chemotherapy with or without radiotherapy, even in the absence of a clear radiological response, leading to improved OS outcomes in this group. Distinct molecular and biological responses to different types of therapies need to be better understood in order to enable the optimal sequencing of specific treatment modalities to further improve OS. In this Review, we describe current treatment strategies for the various clinical stages of PDAC and discuss developments that are likely to determine the optimal sequence of multimodality therapies by integrating the fundamental clinical and molecular features of the cancer.

An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.

TPS771 Background: Curative treatment for potentially resectable (resectable or borderline resectable) pancreatic adenocarcinoma, despite recent advances, leads to only suboptimal outcomes. Recent US national cooperative group trials have demonstrated the safety and feasibility of neoadjuvant chemotherapy (PMID 33475684, PMID 35834226), and also show that the two frontline regimens, FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP), are comparable in this setting. Finally, ability to undergo resection remains the key driver of cure. Therefore, an approach that selects chemotherapy based on early response assessment, to maximize the probability of resection, is likely to improve curative outcomes. Methods: This is a phase II study intended to maximize the probability of surgical resection for pancreatic cancer. Key eligibility requirements include adult patients with a confirmed histopathologic diagnosis of pancreatic carcinoma or adenocarcinoma, an ECOG PS ≤ 1, resectable or borderline resectable disease by central radiology review, no prior therapy for index pancreatic cancer, and adequate bone marrow, liver and kidney function. Treatment includes 4 doses (~ 2 months total treatment time) of FOLFIRINOX (“Chemo1”). After a re-evaluation, using radiologic response, CA19.9 response, and chemotherapy toxicity, patients will either continue with “Chemo1” for another 4 cycles (8 doses) or switch to GnP (“Chemo2”) which will be administered for 4 cycles (12 doses, for ~4 month total treatment time), followed by surgical resection. Primary outcome will measure the proportion of patients undergoing surgical resection using historical dated compared to 32 patients in a current study with a time frame of 16 months. Using historical data, the expected proportion of patients undergoing resection is ~60%. The goal of this study is to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, 32 patients will be needed to demonstrate this difference. Key translational correlatives will include serial circulating tumor DNA assessment and extensive tumor molecular profiling. Clinical trial information: NCT04594772 .

The utility of PD-L1 as a prognostic marker in pancreatic ductal adenocarcinoma (PDAC).

753 Background: The PDAC tumor microenvironment is notoriously immune suppressive, and PD-L1 expression is one mechanism by which tumor cells evade immune surveillance. In PDAC, clinical trials evaluating immunotherapy have not been successful in microsatellite stable tumors, and PD-L1 has not been shown to be predictive of immunotherapy response. Studies suggest that high PD-L1 expression may be associated with worse clinical outcomes and more advanced disease. We aimed to evaluate PD-L1 as a prognostic marker in routine clinical practice using a real-world population of patients with PDAC. Methods: We conducted a retrospective study of patients with PDAC at Mount Sinai Health System from 5/2017 to 12/2021 for whom PD-L1 status by immunohistochemistry (22c3) and combined positive score (CPS) were reported. We assessed the association between PD-L1 expression and overall survival (OS) using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Chi-squared tests were used to evaluate the association between PD-L1 expression and mutations detected by routine next generation sequencing (NGS) using a standard panel. Results: 107 patients were evaluable. At diagnosis, median age was 68 years, 43% of patients were male, 83% had ECOG performance status 0-1, 38% had resectable disease, 14% had borderline resectable disease, and 48% had unresectable disease. Ultimately, 45 patients (42%) underwent surgery. 44% patients had gemcitabine-based initial therapy, perioperatively or as first-line, and 56% had 5FU-based initial therapy. 35% of patients had radiation therapy (RT) at any time. In the entire cohort, 44 (41%) patients had PD-L1 CPS &lt; 1, and 63 patients had CPS ≥ 1. 93 patients had NGS, but no associations were found between PD-L1 status and commonly mutated genes, such as KRAS and SMAD4. For patients who underwent surgery, the median OS (mOS) of patients with PD-L1 CPS ≥ 1 was 46.1 months, and mOS of PD-L1 CPS &lt; 1 was 29.8 months ( P = 0.13). For patients who did not receive surgery, mOS was 12.3 months for CPS ≥ 1 and 15.8 months for CPS &lt; 1 ( P = 0.07). When adjusted for age, gender, ECOG score, stage, type of chemotherapy, RT, and baseline CA 19-9 level, patients who received surgery and had a CPS ≥ 1 had better OS than those who had CPS &lt; 1 (HR 0.22, 95% CI 0.06-0.77, P = 0.02). For patients without resection, CPS ≥ 1 was not associated with OS in the adjusted model (HR 1.52, 95% CI 0.73-3.15, P = 0.26). However, patients with PD-L1 CPS ≥ 10 without surgery had worse OS compared to patients with CPS &lt; 1 in the adjusted model (HR 11.02, 95% CI 2.89-41.96, P &lt; 0.001). Chemotherapy type and receipt of RT did not modify OS based on PD-L1 expression. Conclusions: In resected PDAC, PD-L1 CPS ≥ 1 was independently associated with improved OS, whereas in unresectable PDAC, PD-L1 CPS ≥ 10 was independently prognostic of worse OS. PD-L1 expression is a potential prognostic factor in PDAC and may be a useful and context-dependent biomarker.

Impact of patient characteristics and treatment patterns on outcomes in potentially resectable pancreatic cancer (PC).

681 Background: Treatment of PC remains a challenge, with surgery being the mainstay of potentially curative therapy. Even after surgical resection, however, many patients experience recurrence. There has been a shift toward treating PC as a systemic disease from diagnosis with neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT). This study examines characteristics of real-world patients who were deemed to have resectable (R) or borderline resectable (BR) disease, and how they relate to overall survival (OS). Methods: This is a retrospective analysis of patients in an academic health system who presented for initiation of treatment for PC staged as R or BR. Descriptive data on patient characteristics, performance status (PS), laboratory values, neoadjuvant therapies, recurrence, and mortality were obtained. OS was evaluated using Kaplan-Meier analysis and log-rank tests. Two-sided p-values were calculated. Results: From electronic records at the University of Cincinnati, 129 patients were identified. Median age was 66 with baseline ECOG PS of mostly 0 (86, 67%) or 1 (40, 31%). Primary tumor site was most commonly head of pancreas (104, 81%). Of 129, 55 (43%) patients received surgery upfront; the rest received neoadjuvant therapy (39 nCRT, 35 nCT) with gemcitabine (68%) or 5-fluorouracil (32%) containing regimens. Of those receiving nCRT/nCT, 36 (49%) went on to resection; the rest experienced progression (27, 36%) or toxicities (11, 15%) including death. Of 129, 92 (71%) have died, with median OS of 20.1 months (95% CI 16.4 - 25.0) for the full cohort. On adjusted multivariable analysis, the following were associated with worse OS: failure to undergo resection (HR 5.65, 95% CI 3.17 - 10.09, p&lt;0.0001); receiving &lt;3 cycles nCT (HR 3.00, 95% CI 1.38 - 6.53, p=0.006); baseline CA 19-9 &gt;100 (HR 2.73, 95% CI 1.52 - 4.90, p=0.001); BR disease (HR 2.20, 95% CI 1.27 – 3.81, p=0.005); not receiving RT (HR 1.91, 95% CI 1.04 - 3.53, p=0.038). Regimen choice was not associated with OS. Conclusions: In this real-world PC dataset, surgical resection remains the mainstay of curative therapy. Inadequate nCRT/nCT lead to suboptimal outcomes, likely reflecting patient physiology and disease biology effects. Future trials should focus on maximizing neoadjuvant therapy with the goal of resection.[Table: see text]

Impact of induction chemotherapy on Resectability in Locally advanced oral cavity Carcinomas

Purpose: We aim to assess resectability in patients with locally advanced oral cavity squamous cell carcinomas with induction chemotherapy (ICT). Methods: All stage III-IVB oral squamous cell carcinoma patients with borderline resectable (suspected R1) or unresectable disease (stage IVB, except internal carotid artery encasement or pterygoid plate or skull base involvement) recruited between January 2020 and August 2021 at a tertiary care hospital received 2-3 cycles of ICT (standard TPF regimen) followed by a surgical assessment. The primary aim was to evaluate the proportion of patients that became resectable by ICT. Results: Out of 40 patients, 21 were unresectable (stage IVB disease), and 19 were borderline resectable (stage IVA disease) with doubtful resection margins as per the multi-disciplinary discussion. After chemotherapy, 21 patients became resectable (13 out of 19; and 8 out of 21). Thus, resectability was achieved in 52.5% of patients (32.5% for stage IVA and 20% for stage IVB). The median overall survival (OS) in patients who underwent surgery was 20.5 months (95% CI: 16.95-28.25 months) versus 8.0 months (95% CI: 5.74-13.46 months) in patients who remained unresectable after induction chemotherapy (p=0.0001). Conclusions: In our study, induction chemotherapy leads to improved surgical resection rates with acceptable toxicities in a significant proportion of unresectable locally advanced oral cancers, with improved overall survival significantly.

EP-262 Neoadjuvant imatinib for Resectable Gastrointestinal Stromal Tumors. A State-of-the-art

Abstract Aims Surgical removal remains the cornerstone of primary GIST treatment and complete surgical resection offers prognostic value toward risk of relapse. However, primary tumors, particularly of the stomach, are of advanced size when detected, and multivisceral resection seems to be the treatment of choice. Existing results of recent clinical trials have established the feasibility of neoadjuvant imatinib therapy mainly in unresectable GISTs. Yet, proof of the survival effectiveness of neoadjuvant imatinib therapy in borderline resectable tumors has not been sufficiently demonstrated. Methods A review of the literature was performed to identify the current evidence for preoperative treatment of large GISTs with Imatinib regarding R0 resection and oncological outcome. Results Data supporting benefit of neoadjuvant imatinib are available from several case reports and small retrospective series, most of which include a mix of patients with borderline resectable and unresectable primary disease. In addition, a single-phase II United States Intergroup trial and an Asian phase II trial of neoadjuvant therapy in large stomach tumors, concluded that Neoadjuvant imatinib therapy is preferred for marginally resectable tumors. Progressive disease after neoadjuvant treatment was a rare event, and partial response was achieved in 40–80% of all patients. Conclusion Neoadjuvant therapy with imatinib is safe and recommended for patients with resectable, locally advanced GIST. It may also enable less invasive and organ-sparing surgery, increase the complete resection rate, and avoid the surgical rupture by decreasing the tumor size. Clinical questions still remain about the most appropriate period of pre- and post-operative imatinib administration in the neoadjuvant protocol.