Borderline Resectable Disease Research Articles

The Role of Staging Laparoscopy in Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Aim: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. Results: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14–38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). Conclusion: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.

Complement levels as predictors of survival in pancreatic adenocarcinoma.

315 Background: Novel biomarkers to predict outcomes in pancreatic adenocarcinoma (PDA) are urgently needed. Complement activation, an important mediator of inflammatory processes, has been reported in some solid tumors but its role in PDA is unknown. We evaluated the prognostic role of complement in a prospective cohort of PDA patients. Methods: Blood samples were collected from consenting PDA patients at study entry (prior toany new regimen) in a prospective biorepository protocol at Cleveland Clinic from 2013-2016. Samples were processed for C3a, C4a, and C5a levels using ELISA on serum samples (BD Biosciences). Data on clinical variables, treatment, and survival were collected from medical records. Resectability was defined using Intergroup criteria. Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 48 consecutive patients. Median age was 65 years (range, 41-84); 60% (n=29) were female; 33 (69%) had potentially curable (resectable or borderline resectable) disease. Overall, 43 (93%) received chemotherapy; 22 (46%) received radiation; 29 (60%) underwent surgery. Median follow-up was 17 months. Median OS was 10.9 (1.6-54.5) months. Baseline levels, and associations with stage and OS are shown in Table. Increasing levels of C3a, C4a and C5a were associated with worsened survival (HR 1.00-1.03 per each unit increase in baseline level) despite not being significantly associated with stage. Conclusions: Levels of C3a, C4a, and C5a are detected in nearly all patients with PDA. Increased levels correlate with OS. Complement activation has not been reported previously in PDA and may be a potential therapeutic target. Our findings suggest that complement levels may serve as novel biomarkers. [Table: see text]

Management of Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma is a lethal disease with a poor overall survival. Surgery remains the only potential curative option, and multimodal therapy is typically indicated. Pancreatic cancer can be categorized into four groups according to presentation: resectable disease, borderline resectable disease, locally advanced unresectable disease, and metastatic unresectable disease. Pancreaticoduodenectomy is the most common operation performed for patients with resectable and borderline resectable disease, followed by distal pancreatectomy, and, rarely, total pancreatectomy, with the goal of obtaining an R0 resection. The morbidity associated with these procedures remains high, and thoughtful patient selection is paramount. Postoperative chemotherapy protocols, with or without radiotherapy, are standard, and neoadjuvant therapy is gaining momentum. This review summarizes appropriate management of resectable pancreatic adenocarcinoma. This review contains 12 figures, 5 tables and 49 references

Management of Pancreatic Adenocarcinoma

Pancreatic ductal adenocarcinoma is a lethal disease with a poor overall survival. Surgery remains the only potential curative option, and multimodal therapy is typically indicated. Pancreatic cancer can be categorized into four groups according to presentation: resectable disease, borderline resectable disease, locally advanced unresectable disease, and metastatic unresectable disease. Pancreaticoduodenectomy is the most common operation performed for patients with resectable and borderline resectable disease, followed by distal pancreatectomy, and, rarely, total pancreatectomy, with the goal of obtaining an R0 resection. The morbidity associated with these procedures remains high, and thoughtful patient selection is paramount. Postoperative chemotherapy protocols, with or without radiotherapy, are standard, and neoadjuvant therapy is gaining momentum. This review summarizes appropriate management of resectable pancreatic adenocarcinoma. This review contains 12 figures, 5 tables and 49 references

Neoadjuvant systemic therapy for regionally advanced melanoma.

Patients with regionally advanced melanoma are at high risk of distant failure and unlikely to be cured by surgery alone. Neoadjuvant therapy may provide benefit in these patients. To evaluate our experience with neoadjuvant systemic therapy in high-risk stage III patients. Retrospective review of patients with advanced stage III disease who received neoadjuvant therapy between August 2009 and August 2016 at Mayo Clinic Rochester. Twenty-three cases met our inclusion criteria, 16 with resectable disease and 7 with unresectable disease. No patients with resectable disease and one patient with borderline resectable disease progressed regionally, prohibiting surgical resection. Five of seven patients with unresectable disease were down-staged to a resectable state. Six of twenty-three (26%) had a CR and five are alive at last follow-up. Fifteen of twenty three patients (65%) progressed with a median progression free survival of 11 months; however, the 5 year overall survival estimate was 84%. Neoadjuvant systemic therapy is a reasonable approach for patients with advanced but resectable/borderline resectable disease and the risk of losing regional control is low. Our data also suggest some patients with unresectable disease will be converted to resectable and a complete clinical response to treatment can be obtained in approximately one quater of patients.

Staging of pancreatic cancer: resectable, borderline resectable, and unresectable disease.

Pancreatic ductal adenocarcinoma (PDAC) is a relatively common malignancy that carries an overall poor prognosis, with five-year survival below 10%. Despite ongoing research, surgical resection remains the only potentially curative treatment. Therefore, accurate identification of those patients who would benefit from surgical resection is of paramount importance. High-quality imaging and image interpretation is central to this process. Radiology helps in the determination of whether patients are resectable, borderline resectable, or unresectable and guides treatment planning.

Is distal pancreatectomy with en-bloc celiac axis resection effective for patients with locally advanced pancreatic ductal adenocarcinoma? -Multicenter surgical group study

ObjectivesWe retrospectively investigated the operative outcomes of patients who underwent distal pancreatectomy (DP) for invasive pancreatic ductal adenocarcinoma (PDAC) located at the body and tail. MethodsData from 395 patients with PDAC who underwent DP with margin-negative resection (R0 or R1) were collected from seven high-volume centers in Japan from 2001 to 2012. Among them, 72 patients underwent DP with en-bloc celiac axis resection (DP-CAR). The remaining 323 patients underwent conventional DP with splenectomy (DP-S). To determine the efficacy of DP-CAR, clinicopathological data were compared between the DP-CAR and the DP-S groups. ResultsThe DP-S group consisted mainly of patients with resectable disease (93%), and conversely, all patients in the DP-CAR group had borderline resectable or unresectable disease. The overall morbidity was significantly higher in the DP-CAR group than in the DP-S group (63% vs 47%, respectively; P = 0.017). The median survival time (MST) of the DP-CAR group was significantly shorter than that of the DP-S group (17.5 vs 28.6 months, respectively; P = 0.004). However, the MST of patients in the DP-CAR group (n = 61, 85%) who received adjuvant therapy was significantly longer than that of patients in the DP-S group (n = 65, 20%) who underwent R1 resection (21.9 vs 16.7 months, respectively; P = 0.024). ConclusionDP-CAR followed by adjuvant chemotherapy provided an acceptable overall survival rate in patients with highly advanced PDAC, but should be performed with great caution because of high morbidity. Patients with a high risk of positive surgical margins with DP-S may be candidates for DP-CAR.

Imaging of post-operative pancreas and complications after pancreatic adenocarcinoma resection.

Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related deaths. With surgical resection being the only definitive treatment, improvements in technique has led to an increase in number of candidates undergoing resection by inclusion of borderline resectable disease patients to the clearly resectable group. Post-operative complications associated with pancreaticoduodenectomy and distal pancreatectomy include delayed gastric emptying, anastomotic failures, fistula formation, strictures, abscess, infarction, etc. The utility of dual-phase CT with multiplanar reconstruction and 3D rendering is increasingly recognized as a tool for the assessment of complications associated with vascular resection and reconstruction such as hemorrhage, pseudoaneurysm, vascular thrombosis, and ischemia. Prompt recognition of the complications and distinction from benign post-operative findings such as hepatic steatosis and mesenteric fat necrosis on imaging plays a key role in helping decrease the morbidity and mortality associated with surgery. We discuss, with case examples, some of such common and uncommon findings on imaging to familiarize the abdominal radiologists evaluating post-operative imaging in both acute and chronic post-operative settings.

Stereotactic Body Radiation Therapy in Pancreas Adenocarcinoma Demonstrates Minimal Acute and Late Toxicity

Stereotactic body radiation therapy (SBRT) has been increasingly utilized in the management of pancreatic cancer (PCA). Treatment-related toxicity is a limiting factor in dose escalation and treatment planning. We describe our institutional experience of reportable adverse events following PCA SBRT. A retrospective analysis of 295 PCA patients treated with 5-fraction SBRT from 2010-2016 was performed. All patients included in the cohort had >3 months of documented follow-up from time of SBRT, unless death occurred prior to that time. Toxicities were graded using CTCAE v3.0. Acute and late toxicities were defined as occurring within or after 90 days of SBRT, respectively. The median patient age was 66 (range 36-90). The majority of patients were diagnosed with locally advanced PCA (58%), while the remainder had borderline resectable (26%), resected (12%), or metastatic (2%) disease. The median radiation dose was 33Gy in 5 fractions (range 20-33), and the median PTV was 74cc (range 0.56-313). Volumetric-modulated arc therapy (VMAT) was used in 15% of SBRT cases, and active breathing control (ABC) was implemented in 82%. 47% of the patients received ≥4 months of upfront chemotherapy, and over half (52%) underwent surgical resection. The median follow-up time was 11.9mo (range 1.0-73.3). Late toxicity data was available for 96% of patients. Rates of acute and late grade ≥2 gastritis, fistula, enteritis, or ulcer toxicities were 4.1% and 6.1% respectively. The median time to these toxicities was 2.3mo and 9.1mo. The rates of overall grade ≥3 acute and late toxicities were 10.2% and 15.9%. Among patients who were surgically resected, the grade ≥3 acute and late toxicity rates were 12.5% and 13.8%, and among patients who were not surgical candidates, the rates were 7.7% and 18.9%. Of these grade ≥3 toxicities, the most common included bowel/biliary obstruction (40.3%), gastrointestinal bleed (10.4%), and hepatic/abdominal abscesses (10.4%). There were 6 cases of grade 5 toxicity, all of which were acute. Two patients died of GI bleeds, one during SBRT to liver metastases at an outside institution 2.5 months after pancreas SBRT and the other 1.5 months after surgical resection. For the remaining grade 5 adverse events, patients died after hospitalization for bowel obstruction, septic joint from a fall, acute respiratory distress syndrome 24hrs post-operatively, and post-endoscopic retrograde cholangio-pancreatography-related sepsis. Our institution's experience suggests that pancreas SBRT is well tolerated, with 3 cases (1%) of grade 5 toxicity potentially attributable to SBRT. Further analysis may lead to improved dose constraints and treatment planning.

Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

Background:Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with “borderline resectable disease.” For these patients, an optimal treatment approach is lacking. We report our institution’s experience with borderline resectable PanNETs using multimodality treatment.Methods:We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive.Results:Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression).Conclusions:A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

Alliance for clinical trials in oncology (ALLIANCE) trial A021501: preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas

BackgroundBorderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and 64% of operations achieved an R0 resection. However, the individual contributions of preoperative chemotherapy and radiation therapy to therapeutic outcome remain poorly defined.MethodsIn Alliance for Clinical Oncology Trial A021501, a recently activated randomized phase II trial, patients (N = 134) with a CT or MRI showing a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed anatomic criteria for borderline resectable disease will be randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33–40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy will undergo pancreatectomy and will subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, bolus 5-fluorouracil 400 mg/m2, and infusional 5-fluorouracil 2400 mg/m2 over 2 days for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The primary analysis will compare the 18-month overall survival rate of each arm to a historical control rate of 50%. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site.DiscussionThis study will help define standard preoperative treatment regimens for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials.Trial registrationClinicalTrials.gov: NCT02839343, registered July 14, 2016.

Preoperative CT in patients with surgically resectable pancreatic adenocarcinoma: does the time interval between CT and surgery affect survival?

The preoperative imaging-to-surgery time interval (ISI) influences the risk of unexpected progression (UP) found at surgery for pancreatic adenocarcinoma. We aimed to assess whether ISI influences disease recurrence and/or survival. A single-institution, ethics board-approved retrospective analysis of all patients who underwent attempted resection of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January 2010 and 31st December 2015 was performed. All patients underwent preoperative abdominal computed tomography (CT). Exclusion criteria were borderline resectable disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th June 2016. The population was divided into ISI ≥/<25days. Kaplan-Meier and Cox regression survival analyses were performed. 239 patients underwent surgical exploration. UP was found in 29 (12.1%) and these patients had longer ISI (median 46 vs. 29days, p<0.05). When intention-to-treat analysis was performed, there was no difference in overall survival (OS) between patients with ISI ≥/<25. In those who underwent resection, ISI did not influence disease-free survival (DFS) or OS for PDAC (n=174). For AmpAC (n=36), ISI≥25days was associated with longer OS (p<0.05) but did not influence DFS. Longer ISI was independently associated with improved OS on regression analysis for AmpAC. Performing surgery for resectable pancreatic adenocarcinoma within 25days of abdominal CT reduces the chance of UP but does not confer a survival benefit. For those who undergo resection of AmpAC, a longer ISI was associated with longer OS. This probably represents a more biologically indolent disease in this cohort.

A reduced time to surgery within a ‘fast track’ pathway for periampullary malignancy is associated with an increased rate of pancreatoduodenectomy

IntroductionPancreatoduodenectomy (PD) typically follows preoperative biliary drainage (PBD) despite PBD being potentially harmful. This study evaluated a pathway to avoid PBD within the framework of the UK's NHS. MethodA prospective observational study of jaundiced patients undergoing PD for periampullary cancer. A pathway to provide early surgery without PBD was introduced at the start of the study period. ResultsOver 12 months 61 and 32 patients underwent surgery with and without PBD respectively; 95% of patients in the PBD group had been stented before referral. The time from CT scan to surgery was shorter in the no PBD group (16 vs 65 days, p < 0.0001). Significantly more patients underwent PD in the no PBD group (31/32 vs 46/61, p = 0.009) and venous resection (10/31 vs 4/46, p = 0.014). The sensitivity of initial CT scan to define borderline resectable disease was worse in the PBD group (91 vs 50%, p = 0.042). ConclusionsEarly surgery to avoid PBD is possible within the NHS. By reducing the time to surgery it appears that more patients undergo potentially curative resection. It is desirable to understand why surgery without PBD is not performed routinely as are the development of strategies to support its more widespread practice.

Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer.

4125 Background: Pancreatic cancer (PC) is a challenging target for immunotherapy.Tumor-infiltrating lymphocytes (TILs) do not reach the PC cells in significant numbers due to the presence of stroma and a suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of TILs in the PC microenvironment. We hypothesized that combination of CRT and pembrolizumab can lead to further increase in TILs and their activation. Methods: Patients with resectable or borderline resectable PC have been randomized 2:1 to the investigational treatment (Arm A) to receive pembrolizumab 200mg IV every 3 weeks on days 1, 22, and 43 during concurrent CRT with capecitabine (825 mg/m2 orally twice daily, Monday-Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days) or Arm B to receive only concurrent CRT with capecitabine. Restaging CT scan or MRI is performed at 4-6 weeks after completion of neoadjuvant treatment, and patients with resectable disease will undergo surgical resection. Here we report the preliminary safety data based on 22 enrolled patients. Results: As of February 3-2017,22 patients have been enrolled (14 Arm A and 8 Arm B). 50% of the patients had resectable disease (7 arm A; 4 arm B) and the other 50% had borderline resectable disease (7 Arm A; 4 arm B). Post-neoadjuvant therapy, 6 patients had unresectable disease (3 on each arm), and 14 patients underwent surgery (10 arm A and 4 arm B). There were 7 grade 3 treatment-related toxicities in Arm A (5 patients): 2 grade 3 diarrhea attributed to CRT; 4 grade 3 lymphopenias attributed to pembrolizumab, CRT or the combination; and one patient had elevated alkaline phosphatase probably related to the combination that met the definition of DLT and resolved after holding the treatment and receiving steroids. There was only one grade 3 toxicity on Arm B: lymphopenia attributed to CRT. No grade 4 toxicities have been reported on either arm. There were no major surgical complications reported within 30 days post-surgery. Conclusions: The combination of CRT and pembrolizuamb is safe based on the presented data. Clinical trial information: NCT02305186.

Outcomes of resectable and borderline resectable pancreatic cancer patients in rural practice.

e15712 Background: Accurate selection of patients based on radiological and biological variables is crucial to avoid over treatment and unnecessary R1 resection in pancreatic cancer (PC). Methods: We retrospectively investigated 73 patients diagnosed with PC treated between January 1998 to October 2015. We applied NCCN definitions for Resectable (RD), borderline resectable (BRD) and unresectable disease(URD). Logistic regression was used to identify significant indicators of R0 resection. Odds ratios were used to compare differences of overall survivability by R0 and No surgery. Fisher’s Exact Test was used for significance on all tabulated data. Wilcoxon Rank-Sum was used for the comparison of two medians and Kruskal-Wallis to compare more than two medians, and log-rank test was used to compare Kaplan-Meyer Curves. Results: Radiologically RD comprised 21% (15/73) of total cases, 80% (12/15) of these underwent R0 resection. URD comprised 79% (58/73). Patients presenting with abdominal pain were 2.5 times (Odds Ratio; p = 0.0275) more likely to be URD. The mean tumor size for R0 resectability was 2.28 cm (n = 12). The median CA 19-9 for URD was 1473 vs 162 for RD (p = 0.0124). Stage at presentation and resectability were statistically associated. (p = 0.0002): 100% of Stage 1 (n = 4) and, 27% of Stage 2, (11/41) were resectable. Twenty-three cases were identified as BRD, 21/23 received neoadjuvant chemotherapy, 47.83% had radiological PR, 28.26% had SD and 23.91% PD. There was no association between type of Neoadjuvant treatment (Chemo XRT vs Chemotherapy) and radiological response (p = 0.8798). None of the 21 BRD patients underwent surgery. Median Overall Survival for R0 resection was 22.3 months (95% CI 15.23, 36.50) vs. 5.1 who did not have surgery (95% CI 3.55, 7.57) (p = 0.0010). Conclusions: Nearly 80% patients identified as resectable on imaging underwent R0 resection. Although there were partial responses seen in BRD patients that underwent neoadjuvant treatment eventually none underwent R0 resection. Patients presenting with abdominal pain and high CA19-9 ( &gt; 1400 U/ml) are likely to URD. Early stage and R0 resection were associated with positive outcomes.

Alliance for clinical trials in oncology trial A021501: Preoperative extended chemotherapy vs. chemotherapy plus hypofractionated radiation therapy for borderline resectable adenocarcinoma of the head of the pancreas.

TPS4151 Background: Borderline resectable pancreatic cancers infiltrate into adjacent vascular structures to an extent that makes an R0 resection unlikely when pancreatectomy is performed de novo. In a pilot study, Alliance for Clinical Trials in Oncology Trial A021101, the median survival of patients who received chemotherapy and radiation prior to anticipated pancreatectomy was 22 months, and an R0 resection was achieved in 64% of operations. However, the individual contributions of preoperative chemotherapy and radiation therapy are poorly defined.This study, Alliance for Clinical Oncology Trial A021501, will help define a standard preoperative treatment regimen for borderline resectable pancreatic cancer and position the superior arm for further evaluation in future phase III trials. Methods: In this recently activated randomized phase II trial, 134 patients with a biopsy-confirmed pancreatic ductal adenocarcinoma that meets centrally-reviewed radiographic criteria for borderline resectable disease are randomized to receive either 8 cycles of modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles) or to 7 cycles of modified FOLFIRINOX followed by stereotactic body radiation therapy (33-40 Gy in 5 fractions). Patients without evidence of disease progression following preoperative therapy undergo pancreatectomy and subsequently receive 4 cycles of postoperative modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and infusional 5-fluorouracil 2400 mg/m2 for 4 cycles). The primary endpoint is the 18-month overall survival rate of patients enrolled into each of the two treatment arms. An interim analysis of the R0 resection rate within each arm will be conducted to assess treatment futility after accrual of 30 patients. Secondary endpoints include rates of margin-negative resection and event-free survival. The trial is activated nationwide and eligible to be opened for accrual at any National Clinical Trials Network cooperative group member site. Clinical trial information: NCT02839343.

Phase II study of induction chemotherapy followed by chemoradiotherapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.

Borderline resectable pancreatic cancer: More than an anatomical concept

Borderline resectable pancreatic cancer (BRPC) accounts for about 10–15% of newly diagnosed pancreatic cancer, and its management requires a skilled multidisciplinary team. The main definition of BRPC refers to resectability, but also a high risk of positive surgical margins and recurrence. This raises questions about the value of surgery and suggests an opportunity to utilize preoperative treatment in this subset of patients.Besides technical borderline resectable disease which is defined on anatomical and radiological criteria, there is also a biological borderline resectable disease which is defined on clinical and biological prognostic factors. Technical borderline resectable disease requires tumor shrinkage with aggressive therapy including modern drug combinations +/− radiotherapy to achieve radical surgery. Biological BRPC needs always an early systemic treatment in order to select the best candidates for subsequent radical surgery. It is important to distinguish between these different clinical scenarios, both in clinical practice and for clinical trials design.

Poor Glycemic Control Is Associated with Failure to Complete Neoadjuvant Therapy and Surgery in Patients with Localized Pancreatic Cancer

BackgroundThe impact of glycemic control in patients with pancreatic cancer treated with neoadjuvant therapy is unclear. MethodsGlycated hemoglobin (HbA1c) values were measured in patients with localized pancreatic cancer prior to any therapy (pretreatment) and after neoadjuvant therapy prior to surgery (preoperative). HbA1c levels greater than 6.5% were classified as abnormal. Patients were categorized based on the change in HbA1c levels from pretreatment to preoperative: GrpA, always normal; Gr B, worsened; GrpC, improved; and GrpD, always abnormal. ResultsPretreatment HbA1c levels were evaluable in 123 patients; there were 67 (55%) patients in GrpA, 8 (6%) in GrpB, 22 (18%) in GrpC, and 26 (21%) in GrpD. Of the 123 patients, 92 (75%) completed all intended therapy to include surgery; 57 (85%) patients in GrpA, 4 (50%) patients in GrpB, 16 (72%) patients in GrpC, and 15 (58%) patients in GrpD (p = 0.01). Elevated preoperative carbohydrate antigen 19-9 (CA19-9) (OR 0.22;[0.07–0.66]), borderline resectable (BLR) disease stage (OR 0.20;[0.01–0.45]) and abnormal preoperative HbA1c (OR 0.30;[0.11–0.90]) were negatively associated with completion of all intended therapy. Abnormal preoperative HbA1c was associated with a 2.74-fold increased odds of metastatic progression during neoadjuvant therapy (p = 0.08). ConclusionsElevated preoperative HbA1c is associated with failure to complete neoadjuvant therapy and surgery and a trend for increased risk of metastatic progression.

B35 - Neo-adjuvant treatment in patients with pancreatic cancer with nab-paclitaxel and gemcitabine

Purpose: Pancreatic adenocarcinoma remains one of the deadliest forms of cancer. In this study, we analyzed the efficacy, and toxicity of neo-adjuvant chemotherapy in the treatment of for borderline resectable or unresectable locally advanced pancreatic cancer. Methods: Fifteen patients affected by locally advanced pancreatic cancer treated with nab-paclitaxel and gemcitabine chemotherapy were evaluate. Median age was 55 years (range 47-69 years). The most frequently ECOG performance status were 1 (65%). The majority of the patients has a borderline resectable disease. (65%). Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria.(65%). Results: Within a median follow-up of 16.5 months (range 4-21 months), the majority of the patients received 6-7 of the 9 scheduled cycles of nab-paclitaxel and gemcitabine:: dose reduction were necessary in the 70% of patients. One of patients (15%) achieved a complete response: this patient received also radiotherapy. Partial response were achieved in 15% of patients and stable disease in 75%. Conclusions: Despite the brief period of follow-up and the small number of patients, we conclude that nab-paclitaxel and gemcitabine chemotherapy (+/- radiotherapy) is a valid option in locally advanced pancreatic cancer.