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

PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A 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. RESULTS: In 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. CONCLUSIONS: NAT 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.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Performance and safety of diagnostic EUS FNA/FNB and therapeutic ERCP in patients with borderline resectable and locally advanced pancreatic cancer - results from a population-based, prospective cohort study.

Objective: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS FNA/FNB) and potential endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression are indicated in patients with pancreatic cancer before initation of primary chemotherapy. This study aims to investigate the performance and safety of these two procedures in patients with borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC). Methods: Endoscopy and pathology reports, and hospital records of consecutive patients with a radiological diagnosis of BRPC/LAPC included in a population based, protocol-driven study (NORPACT-2) were reviewed. Results: Of 251 patients, 223 (88.9%) underwent EUS-FNA/FNB, and 133 (53%) underwent ERCP. Repeated EUS attempts were performed in 33 (14.8%), eight (3.6%), and four (1.8%) patients. FNA was performed in 155 procedures, FNB in 30, and combined EUS-FNA/FNB in 83. Diagnostic accuracy was 86.1% for first EUS-FNA/FNB. The cumulative diagnostic accuracy for all attempts was 96%. False positive rate for malignancy was 0.9%. Of a total of 149 ERCP procedures, 122 (81.9%) were successful, and 27 (18.1%) were unsuccessful. Success rate of first ERCP attempt was 80.5% (107/133). Sixteen patients (12%) underwent a second attempt with a success rate of 93.8% (15 of 16). Combined EUS and ERCP was performed in 41 patients. Complications occurred in eight procedures (3%) after EUS-FNA/FNB, 23 procedures (15.3%) after ERCP, and four (9.8%) patients after combined EUS-FNA/FNB and ERCP. Conclusion: EUS-FNA/FNB and ERCP with biliary stenting in patients with BRPC/LAPC demonstrated acceptable performance and safety. Repeat procedures were performed with high success rates. Same session EUS-FNA/FNB and ERCP for biliary decompression is safe.

Protocol digest of a randomized phase III trial comparing S-1-based chemoradiotherapy with/without nivolumab for unresectable locally advanced or borderline resectable pancreatic cancer: JCOG1908E (PENETRATE).

Pancreatic cancer remains a highly lethal disease with a 5-year survival proportion of <10%. Chemoradiotherapy is a treatment option for unresectable locally advanced (UR-LA) or borderline resectable (BR) pancreatic cancer, but its efficacy is not sufficient. Induction of the synergistic effect of irradiation and immune checkpoint inhibitors can be an attractive strategy. An open-label randomized phase III trial has been conducted since October 2020 to confirm the superiority of nivolumab plus S-1-based chemoradiotherapy over S-1-based chemoradiotherapy alone in patients with UR-LA or BR pancreatic cancer. A total of 216 patients will be enrolled in 14 institutions within 3.5 years. The primary endpoint of the safety run-in part is dose-limiting toxicity, and that of the phase III part is overall survival. This trial was registered at the Japan Registry of Clinical Trials as jRCT2080225361 (https://jrct.niph.go.jp/latest-detail/jRCT2080225361).

Proposal of "borderline resectable" colorectal liver metastases based on analysis of risk factors for early surgical failure.

PURPOSE: We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients. METHODS: This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum. RESULTS: Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group. CONCLUSIONS: Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients' oncological condition in borderline-resectable pancreatic cancer.

BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. MATERIALS AND METHODS: From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. RESULTS: HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. CONCLUSIONS: Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

Surgical Intervention After Lenvatinib Treatment in Patients With Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. PATIENTS AND METHODS: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. RESULTS: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks. Progression-free survival (PFS) was significantly longer in patients who underwent surgical intervention than in patients with non-surgical treatment (median, 8.6 vs. 5.1 months, p=0.019). Non-significantly longer overall survival (OS) was also observed in patients with surgical intervention compared to patients with non-surgical treatment (median, unreached vs. 21.0 months, p=0.206). In patients who underwent surgical intervention, two patients had a partial response, and 12 had stable disease according to RECIST ver. 1.1 criteria. The serum alpha-fetoprotein (AFP) level was significantly lower after lenvatinib treatment than before lenvatinib treatment (median, 19.2 vs. 196.5 ng/ml, p=0.0081). Eleven patients underwent curative surgery with a 14% major postoperative complication (Clavien-Dindo ≥IIIa) rate. Patients who exhibited decreases in AFP levels or maintained AFP levels within the normal range during lenvatinib treatment had significantly longer PFS (median, 8.6 vs. 3.0 months, p=0.0009) and OS (median, unreached vs. 12.4 months, p=0.012) compared to those with persistently elevated AFP levels beyond the normal range. CONCLUSION: Surgical intervention after lenvatinib treatment for advanced HCC was associated with longer PFS. Patients exhibiting decreased AFP levels or maintaining AFP levels within the normal limit may be suitable candidates for surgical intervention after lenvatinib treatment for advanced HCC.

The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.

Clinical outcomes in borderline and locally advanced pancreatic cancer with the addition of low-dose-rate brachytherapy to standard of care therapy.

PURPOSE: Surgical resection remains the only curative therapy for pancreatic cancer. Unfortunately, many patients have borderline or unresectable disease at diagnosis due to proximity of major abdominal vessels. Neoadjuvant chemotherapy and radiation are used to down-stage, however, there is a risk that there will be a positive/close surgical margin. The CivaSheet is a low-dose-rate (LDR) brachytherapy device placed at the time of surgery to target the area of highest risk of margin positivity. The purpose of this study is to assess the clinical value of brachytherapy in addition to standard-of-care therapy in pancreatic therapy. METHODS AND MATERIALS: Between 2017 and 2022 patients with borderline and locally advanced pancreatic cancer treated with neoadjuvant chemotherapy and radiation followed by surgical resection were included. There were 2 cohorts of patients: (1) Those who had the LDR brachytherapy device placed at the time of surgery and (2) those who did not. Sixteen of 19 (84%) patients who had brachytherapy were enrolled in a prospective clinical trial (NCT02843945). Patients were matched for comorbidities, cancer staging, and treatment details. The primary outcome was progression-free survival (PFS). RESULTS: Thirty-five patients were included in this analysis, 19 in the LDR brachytherapy group and 16 in the comparison cohort. The 2-year PFS was 21% vs. 0% (p = 0.11), 2-year OS was 26% vs. 13% (p = 0.43), and the pancreatic cancer cause-specific survival was 84% vs. 56% (p = 0.13) in favor of the brachytherapy patients. CONCLUSIONS: Use of LDR brachytherapy at the time of resection shows a trend towards improved progression free and overall survival for patients with borderline or locally advanced pancreatic cancer treated with neoadjuvant chemoradiation.

Prognostic Impact of a Decrease in Serum Carbohydrate Antigen 19-9 Levels After Preoperative Therapy for 4 Months or More for Borderline Resectable Pancreatic Cancer Abutting Major Arteries.

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A).Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P-value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy.Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery.Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients.

Neoadjuvant therapy with intensity-modulated radiotherapy combined with S-1 for borderline-resectable pancreatic cancer.

AIM: We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). METHODS: BRPC patients were treated with IMRT (45 Gy/15fr) combined with two courses of S-1 (40 mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. RESULTS: Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29 vs. 20 months, p = 0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p < 0.001). CONCLUSION: NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

Clinical Outcomes of Surgery After Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma.

Purpose: Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy. Materials and Methods: We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020. Results: Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates and postoperative pancreatic fistula rates (Grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC. Conclusion: Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.

Disparities in neoadjuvant chemotherapy for pancreatic adenocarcinoma with vascular involvement.

Background: Multiagent neoadjuvant chemotherapy (NAT) has been linked with improved survival for locally advanced (LA) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). However, the existence of disparities in its utilization remains to be elucidated. Methods: All adults with PDAC were tabulated from the 2011-2017 Nationwide Cancer Database. Tumor vascular involvement was determined using the clinical T stage and CS_EXTENSION variables. The significance of temporal trends was calculated using Cuzick's non-parametric test. A Cox proportional hazard model was used to assess the impact of NAT utilization on hazard of two-year mortality. A logistic regression model was developed to determine factors associated with receipt of NAT. Results: Of 3811 patients meeting inclusion criteria, 50.8 % received NAT. NAT utilization significantly increased over the study period, from 31.7 % in 2011 to 81.1 % in 2017 (p < 0.001). NAT was associated with significantly reduced two-year mortality (Hazards Ratio 0.34, 95 % Confidence Interval [CI] 0.18-0.67).After adjustment, younger (Adjusted Odds Ratio [AOR] 0.97/year, CI 0.96-0.98) and Black (AOR 0.65, CI 0.48-0.89; ref: White) patients demonstrated reduced odds of NAT. Furthermore, patients with Medicare (AOR 0.73, CI 0.59-0.90; ref: Private) or Medicaid insurance (AOR 0.67, CI 0.46-0.97; ref: Private) had lower odds of NAT, as did those treated at non-academic institutions (Community: AOR 0.42, CI 0.35-0.52, Integrated: 0.68, CI 0.54-0.85) or in the lowest education quartile (AOR 0.52, CI 0.29-0.95; ref: Highest). Conclusions: We identified increasing utilization of NAT for BR/LA pancreatic adenocarcinoma. Despite being linked with significantly reduced two-year mortality, socioeconomic disparities affect odds of NAT.

Radiochemotherapy in Pancreatic Cancer.

Despite the advancements made in oncology in recent years, the treatment of pancreatic cancer remains a challenge. Five-year survival rates for this cancer do not exceed 10%. Among the reasons contributing to poor treatment outcomes are the oligosymptomatic course of the tumor, diagnostic difficulties due to the anatomical location of the organ, and the unique biological features of pancreatic cancer. The mainstay of treatment for resectable cancer is surgery and adjuvant chemotherapy. For unresectable and metastatic cancers, chemotherapy remains the primary method of treatment. At the same time, for about thirty years, there have been attempts to improve treatment outcomes by using radiotherapy combined with systemic treatment. Unlike chemotherapy, radiotherapy has no established place in the treatment of pancreatic cancer. This paper addresses the topic of radiotherapy in pancreatic cancer as a valuable method that can improve treatment outcomes alongside chemotherapy.

Advances in Surgery and (Neo) Adjuvant Therapy in the Management of Pancreatic Cancer.

A multimodality approach, which usually includes chemotherapy, surgery, and/or radiotherapy, is optimal for patients with localized pancreatic cancer. The timing and sequence of these interventions depend on anatomic resectability and the biological suitability of the tumor and the patient. Tumors with vascular involvement (ie, borderline resectable/locally advanced) require surgical reassessments after therapy and participation of surgeons familiar with advanced techniques. When indicated, venous reconstruction should be offered as standard of care because it has acceptable morbidity. Morbidity and mortality of pancreas surgery may be mitigated when surgery is performed at high-volume centers.

Total Neoadjuvant Therapy in Localized Pancreatic Cancer: Is More Better?

Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its advanced stage upon diagnosis and limited treatment options. Surgical resection, the primary curative approach, often results in poor long-term survival rates, leading to the exploration of alternative strategies like neoadjuvant therapy (NAT) and total neoadjuvant therapy (TNT). While NAT aims to enhance resectability and overall survival, there appears to be potential for improvement, prompting consideration of alternative neoadjuvant strategies integrating full-dose chemotherapy (CT) and radiotherapy (RT) in TNT approaches. TNT integrates chemotherapy and radiotherapy prior to surgery, potentially improving margin-negative resection rates and enabling curative resection for locally advanced cases. The lingering question: is more always better? This article categorizes TNT strategies into six main groups based on radiotherapy (RT) techniques: (1) conventional chemoradiotherapy (CRT), (2) the Dutch PREOPANC approach, (3) hypofractionated ablative intensity-modulated radiotherapy (HFA-IMRT), and stereotactic body radiotherapy (SBRT) techniques, which further divide into (4) non-ablative SBRT, (5) nearly ablative SBRT, and (6) adaptive ablative SBRT. A comprehensive analysis of the literature on TNT is provided for both borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC), with detailed sections for each.

Long-term outcomes of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact: Results from a phase II trial.

BACKGROUND/PURPOSE: This study reports the long-term results of a phase II trial evaluating the clinical efficacy of neoadjuvant gemcitabine, nab-paclitaxel, and S1 (GAS) in borderline resectable pancreatic cancer with arterial contact (BRPC-A). METHODS: A multicenter, single-arm, phase II trial was conducted. Patients received six cycles of GAS and patients without progressive disease were intended for R0 resection. RESULTS: Of the 47 patients, 45 (96%) underwent pancreatectomy. At the time of this analysis, all patients were updated with no loss to follow-up. A total of 30 patients died, while the remaining 17 patients were followed for a median of 68.1 months. The updated median overall survival (OS) was 41.0 months, with 2- and 5-year OS rates of 68.0% and 44.6%, respectively. Multivariate analysis in the preoperative model showed that a tumor diameter reduction rate ≥10% and a CA19-9 reduction rate ≥95% after neoadjuvant chemotherapy remained independently associated with favorable survival. In the postoperative multivariate model, no lymph node metastasis, no major surgical complications, and completion of adjuvant chemotherapy were independently associated with improved OS. CONCLUSIONS: This long-term evaluation of the neoadjuvant GAS trial demonstrated the high efficacy of the regimen, suggesting that it is a promising treatment option for patients with BRPC-A.

Analysis of Preoperative Risk Factors for Early Recurrence in Patients After Hepatic Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis even after curative-intent hepatic resection due to a high recurrence rate. The aim of this study was to investigate preoperative risk factors for early recurrence after surgery for ICC, which may help to identify patients who need preoperative chemotherapy. METHODS: We retrospectively analyzed 51 patients who had undergone primary surgery for ICC. We investigated the association of preoperative clinical variables with recurrence within 1 year after resection for ICC. We then created a high-risk ICC score using the identified preoperative factors and investigated the association of the score with disease-free and overall survival. RESULTS: Recurrence within 1 year after surgery for ICC was significantly associated with poor overall survival (P < .01). In the multivariate analysis, preoperative tumor size > 5 cm (P = .03) and elevated C-reactive protein-to-albumin ratio (CAR) (P = .04) were significantly associated with recurrence within 1 year after surgery. A high-risk ICC score of 2 was associated with poor disease-free survival (P < .01) and overall survival (P = .02) compared with a score of 0 or 1. CONCLUSIONS: Our high-risk ICC score, combining preoperative tumor size and CAR, can be an indicator of early recurrence and poor survival in patients after hepatic resection for ICC. Our findings may provide better preoperative risk stratification of patients with ICC, and the high-risk ICC patients may benefit from preoperative therapy.

Update on management of pancreatic cancer: a literature review.

BACKGROUND AND OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality. At the time of diagnosis, majority of patients (80-90%) present with either locally advanced unresectable disease or metastatic disease. Even after curative resection, the recurrence rate remains quite high. This article aimed at reviewing the updated management of pancreatic cancer. METHODS: We identified literature by searching Medline and PubMed from January 2010 to June 2023 using the keywords. KEY CONTENT AND FINDINGS: A multidisciplinary approach is essential to optimize the outcomes for both curable and advanced diseases. Management of pancreatic cancer divided into resectable, borderline resectable, locally advanced, and metastatic diseases. Surgery and adjuvant chemotherapy is a standard treatment approach for resectable pancreatic cancer. The recommended adjuvant chemotherapy regimen for patients with good functional status is modified FOLFIRINOX (5-fluorouracil, folinic acid, irinotecan, and oxaliplatin). The recommended adjuvant chemotherapy regimen for patients with suboptimal functional status is gemcitabine plus capecitabine or monotherapy gemcitabine. The optimal treatment strategy for borderline resectable pancreatic cancer is still uncertain. Traditionally, upfront surgery is the choice of treatment. There is increasing evidence showing benefits of neoadjuvant therapy in borderline resectable pancreatic cancer. However, the optimal neoadjuvant treatment regimen was not certain yet. Advancement of chemotherapy has a positive impact for the survival of advanced disease. For patients with good functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is combination chemotherapy regimens such as FOLFIRINOX, gemcitabine plus nab-paclitaxel. For patients with suboptimal functional status, the recommended first-line systemic chemotherapy for unresectable locally advanced disease or metastatic disease is gemcitabine plus capecitabine or monotherapy gemcitabine. Recently, more researches showed promising results in the use of nanoliposomal irinotecan, targeted agents such as a poly [adenosine diphosphate (ADB)-ribose] polymerase inhibitor, tyrosine receptor kinase (TRK) inhibitors, and immune checkpoint-inhibitors. CONCLUSIONS: Pancreatic cancer is a challenging disease for management. Radical surgery itself is not enough for prolong survival. The improvement of chemotherapy, target agents and immunotherapy with multidisciplinary approach will be the only solution for improvement of survival outcome and quality of life for patients with pancreatic cancer.

Safety and Feasibility of Neoadjuvant-Modified FOLFIRINOX in Elderly Patients with Pancreatic Cancer.

The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase (p = 0.0173) and alanine aminotransferase (p = 0.0378) and nausea (p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate (p = 0.3381), postoperative severe complication rates (p = 0.2450), and postoperative hospital stay (p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC.