Chemotherapy For Resectable Pancreatic Cancer Research Articles

Comparison of adjuvant nab-paclitaxel plus gemcitabine, S-1 and gemcitabine chemotherapy for resectable pancreatic cancer: a real-world study.

A survival benefit has been seen for both adjuvant nab-paclitaxel plus gemcitabine (AG) and S-1 chemotherapy compared to gemcitabine (GEM) for resectable pancreatic cancer in the APACT (2019) and JASPAC01 trials (2016), respectively. However, supporting evidence regarding the effectiveness of AG or S-1 compared to gemcitabine in real-world clinical practice remains lacking. Our study included all 246 pancreatic cancer patients who underwent surgical treatment and received postoperative adjuvant chemotherapy with AG, S-1, or GEM except for those meeting exclusion criteria (R2 resection, neoadjuvant therapy, or synchronous malignancy) at Tianjin Medical University Cancer Institute and Hospital from June 2015 to July 2021. The primary outcome was overall survival (OS) and recurrence-free survival (RFS). In total, 246 patients were included, of whom 54(22%) received adjuvant AG, 103(41%) received adjuvant S-1, and 89(37%) received adjuvant GEM. Adjuvant S-1 was associated with a prolonged OS compared to GEM (median OS S-1 vs GEM: 27.0 vs 20.0 months; HR: 0.65, P = .016) and a significantly prolonged RFS compared to GEM (median RFS S-1 vs GEM: 20.0 vs 8.2 months; HR: 0.58, P = .002). After adjusting for known prognostic factors in multivariate Cox regression analysis, this survival benefit persists and is consistent in most subgroups in our subgroup analysis. However, no statistically significant differences in OS or RFS were seen between patients treated with AG and patients treated with GEM. In this retrospective real-world study, adjuvant S-1 chemotherapy was associated with improved survival compared to GEM while no differences in OS or RFS were observed for AG compared to GEM.

1681P A retrospective real-world study for nimotuzumab plus postoperative adjuvant chemotherapy for resectable pancreatic cancer

1681P A retrospective real-world study for nimotuzumab plus postoperative adjuvant chemotherapy for resectable pancreatic cancer

Alliance A021806: A phase III trial evaluating perioperative versus adjuvant therapy for resectable pancreatic cancer.

TPS4204 Background: The role of neoadjuvant chemotherapy in resectable pancreatic cancer has yet to be defined. Recent phase II trial results demonstrate a median overall survival time (mOS) of only 22.4 months after treatment with perioperative modified FOLFIRINOX (mFOLFIRINOX) with 36% not reaching surgery due to disease progression during neoadjuvant therapy. While potential benefits and shortcomings of neoadjuvant chemotherapy have been well documented, to date, no phase III trial has directly compared a perioperative versus an adjuvant chemotherapy strategy in resectable pancreatic cancer. Alliance for Clinical Trials in Oncology A021806 is an actively accruing randomized controlled phase III trial evaluating the efficacy of perioperative chemotherapy with mFOLFIRINOX in patients with resectable pancreatic cancer. Methods: To qualify for enrollment, patients must have biopsy-proven localized resectable pancreatic adenocarcinoma as defined by the National Comprehensive Cancer Network. Patients must have good performance status (ECOG 0 or 1) and be candidates to receive mFOLFIRINOX treatment. All patients enrolled undergo central radiologic eligibility review for quality control and are then randomized to either Arm 1 which consists of 8 cycles of neoadjuvant mFOLFIRINOX followed by 4 cycles of adjuvant mFOLFIRINOX or Arm 2 which includes upfront surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary endpoint of the trial is overall survival with secondary endpoints evaluating disease-free survival, margin-negative resection rate, surgical complications, and chemotherapeutic adverse events. Additional correlative endpoints include quality of life and radiomic imaging assessments. A total enrollment of 352 patients is planned from the US and Canada; current enrollment for this trial is at 145 patients. An OS interim analysis will be performed when 50% of the events (124) are observed combining the two arms. If the trial continues after interim analysis, the final OS analysis will be performed with a total of 248 events (combined arms). If the Cox model (stratified by tumor location and ECOG PS) comparing OS between arms produces a one-sided p-value < 0.05, then we will conclude that the OS of the perioperative therapy arm is superior to adjuvant therapy. The Alliance A021806 phase III trial aims to define a new standard of care for patients with resectable pancreatic cancer. Clinical trial information: NCT04340141 .

Role for Neoadjuvant Systemic Therapy for Potentially Resectable Pancreatic Cancer.

Despite aggressive adjuvant management, a high percentage of patients who undergo appropriate surgical resection for pancreatic cancer will see their cancer recur and thus will not be cured. An important paradigm shift to achieve better outcomes has been therapy sequence, with neoadjuvant chemotherapy preceding surgery. Patients with a borderline resectable cancer, or patients with a resectable cancer but who have other high-risk features, are ideal candidates to consider for neoadjuvant chemotherapy. Among the high-risk features, a baseline elevated CA 19-9 concentration can be particularly useful, as its response trend during neoadjuvant chemotherapy can offer important insights into the prognosis after surgery. When selecting a neoadjuvant chemotherapy regimen, response data available for the use of FOLFIRINOX and gemcitabine and nabpaclitaxel in the metastatic setting support their use in this space. FOLFIRINOX is perhaps the preferred regimen, given its proven adjuvant benefit and possibly its superior tumor response rate; still, patient tolerance and thus ability to complete recommended treatment must be carefully considered. This review presents the evidence supporting neoadjuvant chemotherapy for resectable pancreatic cancer, the factors to consider when making such a recommendation, the selection of specific regimens, and our institutional approach using these tools.

Neoadjuvant chemotherapy for resectable pancreatic cancer: a new standard of care?

Aim. To evaluate the potential of neoadjuvant chemotherapy in resectable pancreatic cancer based on the results of randomized clinical trials and meta-analyses. Materials and methods. PubMed, Сochrane, EMBASE, GoogleScholar databases were used for bibliographic search with keywords MESH “neoadjuvanttherapy” in combination with “pancreaticcancer”, “resectable”, “pancreaticoduodenectomy”. Results. At the beginning of the 21st century the understanding of pancreatic cancer biology changed. A tumor should be considered a systemic disease even in its early stages, with small size and without lymph node involvement. The necessity for application of neoadjuvant polychemotherapy in patients with resectable tumors is an important issue. The efficacy and safety of the method has been proved. However, a number of questions are still to be answered. Whether neoadjuvant polychemotherapy in patients with resectable pancreatic cancer will be a new achievement of chemotherapy and the standard of care is a matter for future clinical research. Conclusion. Neoadjuvant polychemotherapy in patients with resectable pancreatic cancer is a promising therapy that can improve oncological outcomes of treatment. However, the evidence for this argument is currently insufficient.

Clinical therapeutic effects of neoadjuvant chemotherapy in resectable pancreatic cancer.

677 Background: Results from the phase III Prep-02/JSAP-05 trial demonstrated the efficacy and safety of gemcitabine plus S-1 as neoadjuvant chemotherapy for resectable pancreatic cancer. However, consensus on neoadjuvant chemotherapy for pancreatic cancer has not yet been established, and the effects of neoadjuvant therapy on clinical features of the tumor and improvement in prognosis have not been fully investigated. We aimed to investigate the effect of neoadjuvant chemotherapy on resectable pancreatic cancer. Methods: Between 2013 and 2021, 291 patients who underwent curative resection for resectable pancreatic cancer at our hospital were enrolled. The patients were categorized into groups of those who received neoadjuvant chemotherapy (NAC group: n = 91) and those who received up-front surgery (US group: n = 200). Prognostic predictors were examined in (i) all patients, (ii) US group, and (iii) NAC group. Statistical significance was considered at p < 0.05. Results: The median follow-up periods were 20.7 and 33.2 months in the NAC and US groups, respectively. In the NAC group, 84 of the 91 patients (94.5%) received gemcitabine-based chemotherapy, and three (3.3%) received chemoradiotherapy. There was no difference in overall survival (OS) and recurrence free survival (RFS) between the two groups. In the background, the NAC group had lower preoperative CA19-9 levels, lower lymph node ratio (LNR), and smaller tumor size than in the US group. During multivariable analysis of OS, preoperative CA19-9 levels, LNR, modified Glasgow prognostic score (mGPS), resection margin, and tumor size were identified as possible prognostic predictors in all patients and in the US group, whereas LNR and mGPS were identified in the NAC group. Conclusions: The prognostic significance of preoperative CA19-9 level, tumor size, and LNR were counteracted in the NAC group. These findings may indicate the effect of neoadjuvant chemotherapy for resectable pancreatic cancer.

A multi-institutional, single-arm, phase II trial of neoadjuvant modified-FOLFIRINOX for resectable pancreatic ductal adenocarcinoma.

715 Background: Various peri-operative treatments have been tested to increase the survival of localized PDAC. Even with superior survival among various disease extent of PDAC, resectable PDAC still shows poor outcomes with surgery followed by adjuvant chemotherapy. We report the result of a multi-institutional phase II trial of modified-FOLFIRINOX as neoadjuvant treatment for resectable PDAC. Methods: Treatment naïve pts with histologically confirmed resectable PDAC were enrolled. Resectability was confirmed by both CT and MRI according to NCCN resectability criteria (no arterial tumor contact to celiac axis, SMA or CHA; no tumor contact with SMV or PV or ≤180° contact without vein contour irregularity) in multidisciplinary team meeting. Patients received oxaliplatin 85mg/m2 D1 + leucovorin 400mg/m2 D1 + irinotecan 150mg/m2 D1 + 5-FU 2,000mg/m2 46h continuous infusion, every other week for 6 cycles (12 weeks). Response assessments were performed every 6 weeks using the RECIST criteria version 1.1. Baseline MRI, PET-CT scan, and pre-surgery MRI after 6 cycles were mandatory. The primary endpoint was R0 resection rate. Secondary endpoints included survivals, ORR, safety, resection rate, and correlative biomarker exploration. (NCT05066802). Results: Total of 27 pts were enrolled between May 2020 and Feb 2022. Among total 27 pts, 24 pts underwent curative aim surgery after neoadjuvant treatment (resection rate 88.9%), and 23 pts showed R0 resection (23/27=85.2%), meeting the primary endpoint. Among 27 pts, 19 pts (70.4%) completed the neoadjuvant treatment per protocol. The reasons for neoadjuvant treatment discontinuation included progression of the disease (n=3, 11.1%) and pts withdrawal (n=5, 18.5%). Among 19 patients who underwent surgery per protocol, only one patient was R1 resected (R0 resection rate=94.7%). As of Sep 1, 2022 (median follow-up duration = 15.2 months) 6 pts recurred after surgery (6/19=31.6%). Median recur-free survival was 18.7 months (95%CI 13.6-NR) and median OS was not reached (95%CI 17.6-NR) for the per protocol treated pts. Treatment-related AE (≥G3) occurred in 10 pts (37.0%) including 7 (25.9%) with neutropenia G3-4. Conclusions: Three months of neoadjuvant mFOLFIRINOX was feasible and tolerable for resectable PDAC. Larger randomized trial is needed to validate the impact of neoadjuvant chemotherapy for resectable pancreatic cancer and to find subgroup of pts who would get benefit most from the neoadjuvant treatment. Post hoc genomic analyses with paired pre-neoadjuvant treatment and surgical tissues are ongoing. Clinical trial information: NCT05066802 .

The evolving role of radiation in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer mortality in the United States. Chemotherapy in resectable pancreatic cancer has improved survival by 10-20%. It only converted 10-30% of the borderline resectable and locally advanced pancreatic cancers to be surgically resectable. Radiation therapy has a documented role in managing localized pancreatic cancer, more so for borderline and locally advanced pancreatic cancer, where it can potentially improve the resectability rate of a given neoadjuvant treatment. The role of radiation therapy in resected pancreatic cancer is controversial, but it is used routinely to treat positive margins after pancreatic cancer surgery. Radiation therapy paradigms continue to evolve with advancements in treatment modalities, delivery techniques, and combination approaches. Despite the advances, there continues to be a controversy on the role of radiation therapy in managing this disease. In this review article, we discuss the recent updates, delivery techniques, and motion management in radiation therapy and dissect the applicability of this therapy in pancreatic cancer.

Case of needle tract seeding during preoperative neoadjuvant chemotherapy for resectable pancreatic cancer

Reports of needle tract seeding (NTS) as a complication of endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) have been increasing. To date, most of the reported cases of NTS have been diagnosed during the postoperative follow‐up period. Herein, we report a case of NTS that occurred during preoperative neoadjuvant chemotherapy after EUS‐FNA for resectable pancreatic cancer. The patient underwent transgastric EUS‐FNA for a pancreatic tail tumor. He was diagnosed as having resectable pancreatic cancer and received preoperative neoadjuvant chemotherapy. After completion of the chemotherapy, computed tomography showed a thick‐walled cyst‐like structure appearing between the pancreas and the gastric wall. Combined resection revealed adenocarcinoma invasion into the cyst‐like structure. Based on the clinical course, and surgical and pathological findings, the condition was diagnosed as NTS. It is thus crucial that after EUS‐FNA, a detailed review of the imaging findings be conducted in the preoperative period. If adhesions between the stomach and the pancreas are observed after transgastric EUS‐FNA, combined resection of the gastric wall should be considered.

Skeletal Muscle Loss and Octogenarian Status Are Associated with S-1 Adjuvant Therapy Discontinuation and Poor Prognosis after Pancreatectomy.

Simple SummarySignificant advances in surgical techniques and perioperative care, together with adjuvant chemotherapy, have contributed to the increasing number of patients with pancreatic cancer undergoing surgery. However, the results of some studies suggest that the postoperative complications and mortality might be higher in elderly patients undergoing pancreatectomy. We aimed to identify the utility of S-1 adjuvant chemotherapy in elderly patients with resected pancreatic cancer. In our cohort of 80 patients, including 16 octogenarians, univariate and multivariate analyses revealed that S-1 adjuvant chemotherapy was associated with improved prognosis in patients with pancreatic cancer. However, we also observed that skeletal muscle loss and age of 80 years or older predicted the failure to complete adjuvant chemotherapy with S-1. We propose that evaluation of skeletal muscle mass should be considered as a useful preoperative assessment approach for determining feasibility of adjuvant chemotherapy in elderly patients.The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy <6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy (p < 0.0001 and p = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.

The role of adjuvant chemotherapy in resected pancreatic cancer

Pancreatic cancer has an extremely poor prognosis. Adjuvant chemotherapy is recommended for patients with resected pancreatic cancer. However, optimal adjuvant therapy for resected pancreatic cancer remains controversial. This study aimed to evaluate the efficacy of adjuvant chemotherapy according to the cancer status. We assessed a 253 patients with pancreatic ductal adenocarcinoma who underwent surgery in between January, 2011 and August, 2019 at Kyungpook National University Chilgok Hospital. Among 253 patients, 132 patients with R0 resection and no prior radiation or chemothrapy were retrospectively analyzed. Of the 132 patients analyzed, 67 (50.8%) were men and 65 (49.2%) were women and the median age was 67 (42-85). Overall median survival was 21.8 months. Fifty-seven patients (43.2%) received adjuvant chemotherapy, whereas 75 (56.8%) did not receive adjuvant cheomtherapy after surgery. Although not statistically significant, patients who received chemotherapy seemed to be improved median OS compared with surgery alone (25.6 versus 17.4 months, p = 0.077). Strtified by different lymph node status, the benefit of adjuvant chemotherapy was only seen among the patients with nodal metastasis (HR = 1.78, 95% CI, 1.11-2.87; p = 0.018). This study suggests adjuvant chemotherapy for resected pancreatic cancer is associated with improved survival in selected patients. Adjuvant chemotherapy seems to favorably impact on overall survival for resected pancreatic cancer with nodal metastasis.

Contemporary trials evaluating neoadjuvant therapy for resectable pancreatic cancer

While the use of neoadjuvant therapy is well-accepted in the treatment of borderline resectable and locally advanced pancreatic cancers, the benefit of neoadjuvant chemotherapy in patients with resectable disease has been a topic of debate. Recently, key trials evaluating neoadjuvant chemotherapy for resectable pancreatic cancer have reported results. This review describes key clinical trials evaluating the use of preoperative therapy in patients with technically resectable pancreatic cancer with a focus on their contribution to the available evidence.

Multicenter retrospective observational study of pancreatic cancer with positive peritoneal lavage cytology intended for surgical resection.

695 Background: Although macroscopically curative resection has been performed for pancreatic cancer with positive peritoneal lavage cytology (CY1), the prognosis is poor in most reports. In 2013, the JASPAC01 trial showed that S-1 was superior to Gemcitabine (GEM) as adjuvant chemotherapy for resected pancreatic cancer, and S-1 was also administered to the patients with CY1 who had undergone macroscopically curative resection. Methods: This is a multicenter retrospective observational study that collected data of the patients with pancreatic adenocarcinoma who were diagnosed with CY1 between 2007 and 2015 and had no other noncurable factors. Results: One hundred twenty-seven patients were enrolled from 14 institutions, and 3 were excluded due to liver metastasis or non-adenocarcinoma. The median age was 67 years old and almost patients had PS 0 or 1. Of the 124 patients, 114 underwent macroscopically curative resection and the median overall survival (OS) and recurrence free survival (RFS) were 16.7 and 7.2 months. Of the resected patients, 80 (70%) had no early recurrence and started postoperative adjuvant chemotherapy. Adjuvant chemotherapy regimens were S-1 in 43 patients (54%), GEM in 31 (39%) and others in 6 (7%). The median OS was 21.0 months with S-1 and 19.2 months with GEM (HR: 0.73, 95%CI: 0.44-1.22, P = 0.23), whereas the median RFS was 10.2 and 7.1 months (HR: 0.58, 95%CI: 0.36-0.95, P = 0.03), respectively. Conclusions: After the report of JASPAC01, most patients with pancreatic cancer with CY1 received macroscopically curative resection and treated with S-1 as adjuvant therapy, however the efficacy was insufficient. We should consider appropriate treatment strategies for patients with pancreatic cancer with CY1 intended for surgical resection.

Neoadjuvant treatment of primarily resectable and borderline resectable pancreatic cancer

Due to the increasing prevalence pancreatic cancer represents asevere tumor burden to the population and will be ranked second for cancer-related mortality by the year 2030. If acurative approach is pursued aradical R0 resection of the tumor with sufficient cancer-free resection margins (≥1 mm) should be performed. This has been shown to be associated with aclear benefit for survival. For treatment planning of pancreatic cancer the tumor stage plays apivotal role. In cases of distant metastases apalliative concept is normally initiated. If no distant metastases are detected neoadjuvant treatment can be performed in cases of borderline resectability or locally advanced stages in order to downsize these tumors. In this situation aneoadjuvant treatment has been shown to significantly increase resectability rates and to improve the tumor stage (downstaging). The most recent randomized trials were able to show a significant survival advantage of neoadjuvant treatment for borderline resectable pancreatic cancer. In cases of primarily resectable pancreatic cancer the current standard of care is an upfront resection followed by adjuvant chemotherapy. Initial data are also available indicating asurvival benefit even for resectable pancreatic cancer after neoadjuvant treatment; however, reliable randomized controlled trials showing asurvival advantage of neoadjuvant treatment compared to the current standard treatment of adjuvant chemotherapy following resection are missing. Numerous randomized controlled trials investigating the efficacy of neoadjuvant chemotherapy for resectable pancreatic cancer are currently underway.

Is Surgery-first Still a Reasonable Option in the Era of Neoadjuvant Chemotherapy for Resectable Pancreatic Cancer?

The incidence of pancreatic ductal adenocarcinoma has risen rapidly. By 2030, it is likely to be the second most prevalent cause of death by cancer, following cancer of the lung. Unfortunately, most patients present with advanced disease. In fact, only 20% of patients are candidates for surgery. More research is needed to find dependable treatment options for this disease. Although we wait for more effective treatments to be developed, we continue using chemotherapy, radiation, and surgery-all with less than optimal outcomes. There is a debate about using chemotherapy in the neoadjuvant setting and counter-debate about better outcomes in the adjuvant settings. In the neoadjuvant setting, not everyone is able to make it to surgery; conversely, in the adjuvant setting, not everyone is able to make it to chemotherapy. Drop-out data after surgery are widely available, but similar drop-out rates after neoadjuvant treatment are not widely published. Here, we will analyze the literature to better understand the treatment strategies and outcomes of pancreatic ductal adenocarcinoma. We argue in favor of an upfront surgery and adjuvant therapy strategy for better outcomes and patient quality of life.

National Use of Chemotherapy in Initial Management of Stage I Pancreatic Cancer and Failure to Perform Subsequent Resection.

Chemotherapy is increasingly administered prior to resection in patients with early-stage pancreatic adenocarcinoma, but the national prevalence of this practice is poorly understood. Our objectives were to (1) describe the utilization of upfront chemotherapy management of stage I pancreatic cancer; (2) define factors associated with the use of upfront chemotherapy and subsequent resection; and (3) assess hospital-level variability in upfront chemotherapy and subsequent resection. The National Cancer Database was used to identify patients treated for clinical stage I pancreatic adenocarcinoma. Outcomes were receipt of upfront chemotherapy and surgical resection after upfront chemotherapy. Associations between patient/hospital factors and both initial management and subsequent resection were assessed by multivariable logistic regression. A total of 17,495 patients were included, with 26.6% receiving upfront chemotherapy. Upfront chemotherapy was more likely in patients who were ≥ 80years of age (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.39-1.93), had T2 tumors (OR 2.56, 95% CI 2.36-2.78), or were treated at a low-volume center (OR 2.10, 95% CI 1.63-2.71). Among patients receiving upfront chemotherapy, only 33.5% underwent subsequent resection. Resection was more likely in patients with T1 tumors (OR 1.22, 95% CI 1.04-1.43) and in those treated at high-volume centers (OR 4.03, 95% CI 2.90-5.60). Only 20.4% of hospitals performed resection in > 50% of patients after upfront chemotherapy. Rates of surgical resection after upfront chemotherapy are relatively low, and the proportion of patients who eventually undergo resection varies considerably between hospitals. The use of surgery after upfront chemotherapy in resectable pancreatic cancer should be considered as an internal quality-of-cancer-care measure.

The role of sequential radiation following adjuvant chemotherapy in resected pancreatic cancer.

Optimal adjuvant therapy for resectable pancreatic cancer remains controversial. The Radiation Therapy Oncology Group (RTOG) 0848 is evaluating adjuvant chemotherapy (CT) with or without sequential chemoradiation in the absence of disease progression. In the absence of completed RTOG 0848 data, we addressed the question through a retrospective analysis. The National Cancer Database was queried for non-metastatic, histologically-confirmed pancreatic carcinoma status post resection and adjuvant CT. Patients receiving neoadjuvant therapy were excluded. Multivariable logistic regression was performed to identify factors associated with receipt of sequential radiation therapy (RT) starting at least 4 months after CT, with generation of propensity scores. Log-rank analysis assessed univariate overall survival (OS), while multivariable Cox proportional hazards modeling examined multivariate OS. Six-month landmark analysis was performed to allow for completion of all planned adjuvant therapy. Of 15,661 patients, 14,167 (90.5%) underwent CT alone, and 1,494 (9.5%) received RT. Patients receiving RT had nodal disease and R+ resection more often (P<0.05). Median follow-up was 53.6 months. Sequential RT after adjuvant CT improved outcomes compared to adjuvant CT alone (3-year OS 44.6% vs. 35.3%; P<0.001). On multivariate analysis, sequential RT continued to improve OS (HR =0.68; 95% CI, 0.63-0.73; P<0.001). After propensity score adjustment, the benefit of sequential RT was maintained (HR =0.68, P<0.001). Sequential RT after adjuvant CT for resected pancreatic cancer was associated with improved survival. The final results of RTOG 0848 are eagerly awaited to provide definitive evidence in this clinical scenario.

Neoadjuvant plus adjuvant or only adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer - the NEONAX trial (AIO-PAK-0313), a prospective, randomized, controlled, phase II study of the AIO pancreatic cancer group

BackgroundEven clearly resectable pancreatic cancer still has an unfavorable prognosis. Neoadjuvant or perioperative therapies might improve the prognosis of these patients. Thus, evaluation of perioperative chemotherapy in resectable pancreatic cancer in a prospective, randomized trial is warranted. A substantial improvement in overall survival of patients with metastatic pancreatic cancer with FOLFIRINOX and nab-paclitaxel/gemcitabine vs standard gemcitabine has been demonstrated in phase III-trials. Indeed nab-paclitaxel/gemcitabine has a more favorable toxicity profile compared to the FOLFIRINOX protocol and appears applicable in a perioperative setting.MethodsNEONAX is an interventional, prospective, randomized, controlled, open label, two sided phase II study with an unconnected analysis of the results in both experimental arms against a fixed survival probability (38% at 18 months with adjuvant gemcitabine), NCT02047513. NEONAX will enroll 166 patients with resectable pancreatic ductal adenocarcinoma (≤ cT3, N0 or N1, cM0) in two arms: Arm A (perioperative arm): 2 cycles nab-paclitaxel (125 mg/m2)/gemcitabine (1000 mg/m2, d1, 8 and 15 of an 28 day-cycle) followed by tumor surgery followed by 4 cycles nab-paclitaxel/gemcitabine, Arm B (adjuvant arm): tumor surgery followed by 6 cycles nab-paclitaxel/gemcitabine. The randomization (1:1) is eminent to avoid allocation bias between the groups. Randomization is stratified for tumor stage (ct1/2 vs. cT3) and lymph node status (cN0 vs. cN1). Primary objective is disease free survival (DFS) at 18 months after randomization. Key secondary objectives are 3-year overall survival (OS) rate and DFS rate, progression during neoadjuvant therapy, R0 and R1 resection rate, quality of life and correlation of DFS, OS and tumor regression with pharmacogenomic markers, tumor biomarkers and molecular analyses (ctDNA, transcriptome, miRNA-arrays). In addition, circulating tumor-DNA will be analyzed in patients with the best and the worst responses to the neoadjuvant treatment. The study was initiated in March 2015 in 26 centers for pancreatic surgery in Germany.DiscussionThe NEONAX trial is an innovative study on resectable pancreatic cancer and currently one of the largest trials in this field of research. It addresses the question of the role of intensified perioperative treatment with nab-paclitaxel plus gemcitabine in resectable pancreatic cancers to improve disease-free survival and offers a unique potential for translational research.Trial registrationClinicalTrials.gov: NCT02047513, 08/13/2014.

Hope and frustration of neoadjuvant chemotherapy for resectable pancreatic cancer

There are many shortcomings in the existing strategy for the treatment of resectable pancreatic cancer by surgery combined with postoperative adjuvant chemotherapy.Neoadjuvant chemotherapy has the effects of clearing micrometastases, improving the margins, and assessing chemosensitivity of resectable pancreatic cancer.Currently, neoadjuvant chemotherapy is still mainly used for borderline resectable pancreatic cancer and unresectable pancreatic cancer.However, resectability assessment, patients selection, choice of chemotherapy regimens, assessment of chemotherapy response, chemotherapy cycles, and timing for surgery are still undetermined.At the same time, the mainstream regimens are highly toxic, expensive, and have a long course of treatment.It is still a small number of patients that can successfully pass the chemotherapy screening to undergo resection.It should be recognized that pancreatic cancer is still a chemotherapy-insensitive tumor.There are many unreasonable ways to use neoadjuvant chemotherapy in pancreatic cancer like chemotherapy-sensitive tumors.We need to explore more scientific, economical and applicable approaches for neoadjuvant chemotherapy on resectable pancreatic cancer.

High compliance with guideline recommendations but low completion rates of adjuvant chemotherapy in resected pancreatic cancer: A cohort study.

BackgroundAdjuvant chemotherapy (adCx) is an integral part of multimodal treatment in resected pancreatic ductal adenocarcinoma (PDAC) and is recommended by the German S3 guideline since 2007 in all patients. We aimed to investigate the impact of this guideline at our institution.MethodsIn 151 of 403 pancreatic resections performed histopathology revealed PDAC. Follow-up data were available from 143 patients (95%) representing our study group. The rate of recommended, initiated and fully completed adCx was analyzed for period 1 (09/2003–07/2007) and period 2 (08/2007–08/2014).ResultsOur study group comprised 49 patients in period 1 and 94 patients in period 2. AdCx was recommended, initiated and completed in 42/49 (86%), 34/49 (69%) and 22/49 (45%) patients in period 1 and in 93/94 (99%), 78/94 (83%) and 49/94 (52%) patients in period 2, respectively. Only the increase in recommendations for adCx was statistically significant (p = 0.0024). Overall, only 50% (71/143) of patients fully completed the Cx protocol. Completed adCx resulted in a significantly longer (p = 0.0225) overall survival compared to patients with incomplete or without adCx. Multiple logistic regression revealed adCx (p = 0.0046) as independent factor of survival. The hazard ratio for fully completed adCx was 0.406 and for incomplete adCx 0.567.ConclusionOur results indicate a high acceptance of the S3-guidline recommendation for adCx in resected PDAC in a routine setting, which, however, is completed in only 50% of all patients. Fully completed adCx had the most powerful effect on improving overall survival.