Neoadjuvant treatment of pancreatic ductal adenocarcinoma: present and future (original) (raw)
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Multimodal treatment of resectable pancreatic ductal adenocarcinoma
Critical Reviews in Oncology/Hematology, 2017
After a timing preoperative staging, treatment of resectable pancreatic adenocarcinoma (PDAC) includes surgery and adjuvant therapies, the former representing the initial therapeutic option and the latter aiming to reduce the incidence of both distant metastases (chemotherapy) and locoregional failures (chemoradiotherapy). Herein, we provide a critical overview on the role of multimodal treatment in PDAC and on new opportunities related to current more active poli-chemotherapy regimens, targeted therapies, and the more recent immunotherapy approaches. Moreover, an analysis of pathological markers and clinical features able to help clinicians in the selection of the best therapeutic strategy will be discussed. Lastly, the role of neoadjuvant treatment of initially resectable disease will be considered mostly in patients whose malignancy shows morphological but not clinical or biological criteria of resectability. Depending on the results of these investigational studies, today a multidisciplinary approach can offer the best address therapy for these patients.
Annals of Diagnostic Pathology, 2012
In patients with pancreatic ductal adenocarcinoma (PDA) who received neoadjuvant therapy and pancreatectomy, pathologic complete response (pCR) is rarely observed and the prognostic significance of pCR is not clear. In this study, we reported 11 patients with pCR (2.5%) from 442 patients with PDA who received neoadjuvant treatment and pancreatectomy from 1995 to 2010. There were 6 men and 5 women with median age of 61 years. Four patients had either synchronous or prior history of extra-pancreatic cancer. Five patients received neoadjuvant chemotherapy followed by chemoradiation, and 6 received chemoradiation alone. Ten patients had pancreaticoduodenectomy and one had distal pancreatectomy. Scar and chronic pancreatitis consistent with therapy effect were present in all cases (100%). Pancreatic intraepithelial neoplasia 3 (Pan IN3)/carcinoma in situ was present in 5 cases, PanIN1 and PanIN2 in 5 cases. However, no residual invasive carcinoma or lymph node metastasis was identified in all cases. Follow-up information was available in 10 patients. Follow-up time ranges from 6 to 194 months (median, 63 months). During follow-up, three patients died of other causes and one developed a second primary PDA in the tail of pancreas at 84 months after initial pancreaticoduodenectomy and died at 105 months after the initial diagnosis of PDA. The other 6 patients were alive with no evidence of disease. Patients with pCR had better survival than those who had post-therapy stage I or IIA
Neoadjuvant treatment in non- metastatic pancreatic cancer, an option to be considered
Gastroenterology & Hepatology: Open Access
Pancreatic adenocarcinoma is one of the malignancies with worse prognosis among all solid tumors. It is the third cause of death due to cancer in the United States, with an estimated incidence of 48.960 new cases by 2015 and 40.560 deaths during the same year. Incidence and mortality are slightly higher in men than in women. 1
Cureus, 2015
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types. We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and offprotocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.
Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma
Gastroenterology Review, 2016
Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds-pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma.
Biomedicines
Pancreatic cancer is the seventh leading cause of cancer-related mortality in both sexes across the globe. It is associated with extremely poor prognosis and remains a critical burden worldwide due to its low survival rates. Histologically, pancreatic ductal adenocarcinoma (PDAC) accounts for 80% of all pancreatic cancers; the majority of which are diagnosed at advanced stages, which makes them ineligible for curative surgery. Conventional chemotherapy provides a five-year overall survival rate of less than 8% forcing scientists and clinicians to search for better treatment strategies. Recent discoveries in cancer immunology have resulted in the incorporation of immunotherapeutic strategies for cancer treatment. Particularly, immune-checkpoint inhibitors, adoptive cell therapies and cancer vaccines have already shifted guidelines for some malignancies, although their efficacy in PDAC has yet to be elucidated. In this review, we summarize the existing clinical data on immunotherapy c...
Advances in Pancreatic Ductal Adenocarcinoma Treatment
Cancers, 2021
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest malignancies among all cancers. Despite curative intent, surgery and the use of standard cytotoxic chemotherapy and radiation therapy, PDAC remains treatment-resistant. In recent years, more contemporary treatment modalities such as immunotherapy via checkpoint inhibition have shown some promise in many other malignancies, yet PDAC still eludes an effective curative treatment. In investigating these phenomena, research has suggested that the significant desmoplastic and adaptive tumor microenvironment (TME) of PDAC promote the proliferation of immunosuppressive cells and act as major obstacles to treatment efficacy. In this review, we explore challenges associated with the treatment of PDAC, including its unique immunosuppressive TME. This review examines the role of surgery in PDAC, recent advances in surgical approaches and surgical optimization. We further focus on advances in immunotherapeutic approaches, including ...
Current Oncology
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemo...
Surgery today, 2017
Preoperative chemoradiotherapy (CRT) is a novel, emerging treatment strategy for pancreatic ductal adenocarcinoma (PDAC), but it remains unclear whether post-surgery adjuvant chemotherapy is feasible following preoperative CRT. This retrospective study evaluates the feasibility of adjuvant therapy after preoperative CRT. The subjects of this study were 99 consecutive patients who underwent pancreatectomy for PDAC between January, 2007 and February, 2013 in our hospital. Sixty patients received preoperative CRT: as gemcitabine (GEM) and 40 Gy radiation in 28 (G-CRT group), and as GEM, S-1, and 50.4 Gy radiation in 32 (GS-CRT group). We also evaluated 39 patients who underwent surgery alone (SA group). We investigated adjuvant chemotherapy induction and completion rates and the frequency of adverse events rated ≥grade 3, based on Common Terminology Criteria for Adverse Events (version 4.0) in all three groups. In the G-CRT, GS-CRT, and SA groups, the induction rates were 78 % (22/28),...
Neoadjuvant therapy in resectable pancreatic cancer: a critical review
Cancer treatment reviews, 2013
Pancreatic cancer is among the deadliest tumors. Due to intrinsic chemo- and radio-resistance, surgical resection remains the only chance for cure. However surgery alone is unable to considerably improve survival and complementary chemotherapy and radiotherapy in a multimodal approach have been tested. Adjuvant chemotherapy yielded a modest outcome improvement, whereas the use of adjuvant chemoradiation is highly controversial. In this scenario, the neoadjuvant approach has a strong theoretical rationale, but limited information on the efficacy of this strategy is available. This review critically overviews the current knowledge, the rationale, the available data and information on neoadjuvant treatment in resectable pancreatic cancer. The very early systemic dissemination of pancreatic cancer endorses the rationale for an up-front use of systemic therapy. However, evidence collected so far depends on retrospective data, small case series that did not balance the different character...