scholarly journals Neoadjuvant Treatment for Pancreatic Adenocarcinoma: A False Promise or an Opportunity to Improve Outcome?

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4396
Author(s):  
Shelize Khakoo ◽  
Angelica Petrillo ◽  
Massimiliano Salati ◽  
Abdul Muhith ◽  
Jessica Evangelista ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Tumor Biology ◽  
Neoadjuvant Treatment ◽  
Significant Proportion ◽  
Treatment Strategies ◽  
Poor Performance ◽  
Ductal Adenocarcinoma ◽  
Current Evidence ◽  
R0 Resection

Pancreatic ductal adenocarcinoma (PDAC) has an aggressive tumor biology and is associated with poor survival outcomes. Most patients present with metastatic or locally advanced disease. In the 10–20% of patients with upfront resectable disease, surgery offers the only chance of cure, with the addition of adjuvant chemotherapy representing an established standard of care for improving outcomes. Despite resection followed by adjuvant chemotherapy, at best, 3-year survival reaches 63.4%. Post-operative complications and poor performance mean that around 50% of the patients do not commence adjuvant chemotherapy, and a significant proportion do not complete the intended treatment course. These factors, along with the advantages of early treatment of micrometastatic disease, the ability to downstage tumors, and the increase in R0 resection rates, have increased interest in neo-adjuvant treatment strategies. Here we review biomarkers for early diagnosis of PDAC and patient selection for a neo-adjuvant approach. We also review the current evidence for different chemotherapy regimens in this setting, as well as the role of chemoradiotherapy and immunotherapy, and we discuss ongoing trials.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

scholarly journals Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions

2019 ◽  
Vol 20 (18) ◽  
pp. 4543 ◽  
Author(s):  
Maximilian Brunner ◽  
Zhiyuan Wu ◽  
Christian Krautz ◽  
Christian Pilarsky ◽  
Robert Grützmann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
R0 Resection ◽  
Molecular Testing ◽  
Borderline Resectable ◽  
Tumor Biopsies

Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Outcomes with FOLFIRINOX for locally advanced pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 256-256
Author(s):  
Brian A. Boone ◽  
Jennifer Steve ◽  
Alyssa M. Krasinskas ◽  
Amer H. Zureikat ◽  
Barry C. Lembersky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Response Rates ◽  
Biologically Active ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Borderline Resectable

256 Background: Trials examining the use of FOLFIRINOX in metastatic pancreatic ductal adenocarcinoma demonstrate significantly higher response rates compared to gemcitabine-based regimens. These high response rates may be particularly important for patients with locally advanced pancreatic ductal adenocarcinoma (LAPD), in which there is currently limited experience with FOLFIRINOX. We examined the outcomes of patients with LAPD treated with neoadjuvant FOLFIRINOX at our high volume clinic. Methods: Retrospective review of a prospectively maintained pancreatic cancer database was used to identify patients who were recommended neoadjuvant treatment with FOLFIRINOX. Clinical outcomes were reviewed. Resectability was determined using SSO criteria. Results: Between 2/2011 and 9/2012 FOLFIRINOX was recommended for 25 patients with LAPD, 13 (52%) unresectable (UR) and 12 (48%) borderline resectable (BR). Median age was 59. 4 patients (16%) either refused treatment or were lost to follow up. 21 patients (84%) were treated with a median of 4.7 cycles (Range: 2-8). 5 patients (24%) required dose reductions secondary to toxicity. 2 patients (9%) were unable to tolerate treatment and 3 patients (14%) had disease progression on treatment. Of the remaining 16 patients, 13 patients (62%) displayed a radiologic response allowing for surgical exploration, 4 (31%) of which were initially unresectable. 6 of these patients (29%) received additional chemotherapy and/or radiation therapy prior to surgery. Peritoneal metastases were discovered at surgery in 2 (8%) patients. Of the patients who were BR, 7/8 (88%) had a R0 resection. Of the 10 UR patients, 3 (33%) underwent surgical resection, with 2 (20%) R0 resections. Overall R0 resection rate was 43%. A total of 4 patients (19%) demonstrated a major pathologic response (2 complete responses and 2 near complete responses) and 8 other patients (73%) had some pathological response. Conclusions: FOLFIRINOX alone or as part of multimodality approach is a biologically active regimen in LAPD with encouraging R0 resection rates, especially in BR LAPD. Further research is needed to determine the utility of additional chemoradiotherapy with FOLFIRINOX and to identify predictors of response in UR patients.

Combined chemotherapy and EUS-guided intra-tumoral 32-P implantation for locally advanced pancreatic ductal adenocarcinoma: a pilot study

Endoscopy ◽  
2021 ◽  
Author(s):  
Jeevinesh Naidu ◽  
Dylan Bartholomeusz ◽  
Joshua Zobel ◽  
Romina Safaeian ◽  
William Hsieh ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Adelaide Hospital ◽  
Response To Treatment ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
R0 Resection ◽  
Royal Adelaide Hospital ◽  
Combined Chemotherapy ◽  
Radioactive Phosphorus ◽  
18Fdg Pet

Aim: This study evaluated clinical outcomes of combined chemotherapy and Endoscopic Ultrasound (EUS) guided intra-tumoral radioactive phosphorus-32 (32P OncoSil) implantation in locally advanced pancreatic adenocarcinoma (LAPC). Methods: Consecutive patients with a new histological diagnosis of LAPC were recruited over 20 months. Baseline CT and 18FDG PET-CT were performed and repeated after 12 weeks to assess response to treatment. Following 2 cycles of conventional chemotherapy, patients underwent EUS-guided 32P OncoSil implantation followed by a further six cycles of chemotherapy. Results: Twelve patients with LAPC (8M:4F; median age 69 years, IQR 61.5-73.3) completed the treatment. Technical success was 100% and no procedural complications were reported. At 12 weeks, there was a median reduction of 8.2cm3 (95% CI 4.95-10.85; p=0.003) in tumour volume, with minimal or no 18FDG uptake in 9 (75%) patients. Tumour downstaging was achieved in 6 (50%) patients, leading to successful resection in 5 (42%) patients, of which 4 patients (80%) had clear (R0) resection margins. Conclusions: EUS guided 32P OncoSil implantation is feasible and well tolerated and was associated with a 42% rate of surgical resection in our cohort. However, further evaluation in a larger randomized multicenter trial is warranted. (32P funded by OncoSil Medical Ltd, equipment and staff funded by the Royal Adelaide Hospital, ClinicalTrials.gov number, NCT03003078).

740 CAMRELIZUMAB IN COMBINATION WITH PREOPERATIVE CHEMOTHERAPY FOR LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A SINGLE-ARM, OPEN-LABEL, PHASE II STUDY

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Yu Qi ◽  
Xiangrui Meng ◽  
Qingxia Fan
Keyword(s):  
Phase Ii ◽  
Preoperative Chemotherapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Reduction Rate ◽  
Complete Response ◽  
Pathologic Response ◽  
R0 Resection ◽  
Efficacy And Safety

Abstract   At present, ESCC has a dismal prognosis with huge unmet clinical needs. With the potential benefit of combining PD-1 inhibitor with nCT, we conducted a phase II trial to assess the efficacy and safety of Camrelizumab plus nCT for locally advanced ESCC. Methods 45 patients (pts) with histologically confirmed stage II/III/IVa(cT2-4aN0-3 M0) ESCC were enrolled from February 2020 to March 2021.The study was divided into two stages, stage1: we administered 1 cycle of Camrelizumab for induction therapy (200 mg q2 weeks); stage2: pts received 2 cycle of Camrelizumab (200 mg every 3 weeks) plus docetaxel and nedaplatin, followed by surgery within 4 ~ 6 weeks after neoadjuvant therapy completion. Primary endpoint was major pathologic response (MPR). Secondary endpoints included pathologic complete response (pCR), R0 resection rate, disease-free survival (DFS) and overall survival (OS). Results At the cutoff date of Mar 9, 2021, 45 eligible pts were enrolled, neoadjuvant treatment was completed in 39 pts. Thus far 32 pts were resected, all patients underwent an R0 resection. Postoperative pathology showed that TNM stage decreased in 28 pts with 87.5% reduction rate. 19 pts (59.38%) reached major pathologic response, 9 pts (28.13%) reached pathologic complete response (no surgery related mortality). A total of 75.56% had AEs with 13.33% of grade ≥ 3 AEs. Date for median DFS and OS were not matured. Conclusion Camrelizumab in combination with preoperative chemotherapy followed by surgery for locally advanced ESCC showed promising downstaging effect and MPR with good tolerance, and its efficacy and safety could be further studied in later trials. Clinical trial information: NCT03917966.

Phase II study of perioperative toripalimab in combination with FLOT in patients with locally advanced resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4050-4050
Author(s):  
Hongli Li ◽  
Jingyu Deng ◽  
Shaohua Ge ◽  
Fenglin Zang ◽  
Le Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Death Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
R0 Resection ◽  
Combination Regimen

4050 Background: FLOT is the standard perioperative treatment for resectable gastric /gastroesophageal junction (GEJ) adenocarcinoma. However, patient’s outcome is still poor. Toripalimab, a humanized IgG4 monoclonal antibody against programmed cell death receptor-1 (PD-1), has shown remarkable clinical efficacy in various cancers. This trial evaluates the addition of Toripalimab to FLOT for resectable patients. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥cT2 or cN+) were enrolled to receive 4 pre-and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2w). The primary endpoint was pathological complete response rate (pCR). The secondary endpoints included major pathological (complete and nearly complete) response (MPR), and R0-resection rate, 3-year disease-free survival rate, overall survival, and adverse events. Results: In total, of 36 patients were enrolled from June 2019 through Dec 2020. Male, 66.7%; median age, 60y; cT3 8.3%, T4, 83.3%; cN+ 88.9%; GEJ 47%; MSI-H, 5.6%, Her-2neu-positive, 5.6%, EBER-positive, 5.6%). Two patients refused surgery, six patients have not yet completely neoadjuvant treatment. 100% of patients completed the 4 pre-cycle. Patients who had received gastrectomy after neoadjuvant treatment (n=28) were included in this analysis. 6 (21%) patients had operations involving a thoracic approach (oesophagogastrectomy with two field lymphadenectomy), 21 (75%) gastrectomy with D2 lymphadenectomy. 8 (29%) evaluable patients had Clavien-Dindo grade II post-operative complications and 2 (7%) grade IIIA complications; one patient had an anastomotic leakage that was treated endoscopically. There were no emergency re-operations. All 28 patients achieved R0-resection and were discharged home after a median of 12 days (range:7-63) in hospital. 7 （25%）patients achieved pCR (TRG1a) and 12 (42.9%) patients achieved major pathologic response (MPR, TRG1a/b). Treatment-related adverse events (TRAEs) to any drug were reported in 30 (94%) patients. Mostly TRAEs were grade 1-2, the grade 3 or 4 TRAEs included neutropenia (34%), neutropenia (25%), lymphopenia (3%), Alanine aminotransferase increased (3%), hypokalemia (3%) and anaemia (3%). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate and well tolerated safety profile in patients with resectable gastric/GEJ adenocarcinoma. This combination regimen might present a new option for patients with locally advanced, resectable gastric/GEJ adenocarcinoma. Clinical trial information: NCT04354662.

scholarly journals Current locoregional therapies and treatment strategies in hepatocellular carcinoma

2020 ◽  
Vol 27 (S3) ◽  
Author(s):  
L. Cardarelli-Leite ◽  
A. Hadjivassiliou ◽  
D. Klass ◽  
J. Chung ◽  
S.G.F. Ho ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Percutaneous Ablation ◽  
Transarterial Radioembolization ◽  
Combined Use ◽  
Liver Morphology ◽  
Locoregional Therapies ◽  
Bridging To Transplant

Locoregional therapies (LRT) play an important role in the treatment of hepatocellular carcinoma (HCC), with the aim of increasing overall survival while preserving liver function. Different forms of LRT are available and choosing which one is best will depend on technical aspects, liver morphology, tumor biology, and patient’s symptoms. The purpose of this review article is to provide an overview of the current evidence regarding the use of percutaneous ablation, transarterial chemoembolization and transarterial radioembolization for the curative or palliative treatment of HCC. Special situations are also reviewed, including the combined use of systemic therapy with LRT; indications and techniques for bridging to transplant and downstaging; and the use of LRT to treat patients with HCC and macrovascular invasion.

scholarly journals Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

scholarly journals Conversion Surgery for Advanced Pancreatic Cancer

2019 ◽  
Vol 8 (11) ◽  
pp. 1945
Author(s):  
Thomas Hank ◽  
Oliver Strobel
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Palliative Therapy ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Conversion Surgery ◽  
Radiological Criteria ◽  
Intention To Treat ◽  
Conversion Rates

While primarily unresectable locally advanced pancreatic cancer (LAPC) used to be an indication for palliative therapy, a strategy of neoadjuvant therapy (NAT) and conversion surgery is being increasingly used after more effective chemotherapy regimens have become available for pancreatic ductal adenocarcinoma. While high-level evidence from prospective studies is still sparse, several large retrospective studies have recently reported their experience with NAT and conversion surgery for LAPC. This review aims to provide a current overview about different NAT regimens, conversion rates, survival outcomes and determinants of post-resection outcomes, as well as surgical strategies in the context of conversion surgery after NAT. FOLFIRINOX is the predominant regimen used and associated with the highest reported conversion rates. Conversion rates considerably vary between less than 5% and more than half of the study population with heterogeneous long-term outcomes, owing to a lack of intention-to-treat analyses in most studies and a high heterogeneity in resectability criteria, treatment strategies, and reporting among studies. Since radiological criteria of local resectability are no longer applicable after NAT, patients without progressive disease should undergo surgical exploration. Surgery after NAT has to be aimed at local radicality around the peripancreatic vessels and should be performed in expert centers. Future studies in this rapidly evolving field need to be prospective, analyze intention-to-treat populations, report stringent and objective inclusion criteria and criteria for resection. Innovative regimens for NAT in combination with a radical surgical approach hold high promise for patients with LAPC in the future.

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