**Neoadjuvant Treatment**

**Chapter 9**

**Provisional chapter**

**Neoadjuvant Treatment for Nonmetastatic Pancreatic**

Pancreatic adenocarcinoma is one of the most lethal malignancies among solid tumors. Unfortunately, several patients are diagnosed at metastatic stage or with unresectable disease due to vascular compromise involving the pancreas without any chance of curative treatment. There are also two other groups of patients: resectable patients at upfront diagnosis and "borderline resectable" pancreatic cancer patients. This last group represents those patients where surgery is not always possible without a preoperative treatment allowing surgeons to perform an R0 resection. Achieving an R0 resection is the only curative option for pancreatic cancer patients; nevertheless, many R0-resected patients will relapse within 2 years from surgery. Despite adjuvant treatment, reported median overall survival is only 28 months for patients with resectable pancreatic adenocarcinoma; thus, neoadjuvant treatment has been explored in order to improve survival. We aim to describe the controversial reported data and to show the recommendations that are suggested for these patients; however, we need to remark that there is no strong data that support neoadjuvant treatment. Currently, clinical trials are ongoing, and probably soon this approach will become a standard of care among borderline resectable patients and probably in selected resectable patients too.

**Keywords:** neoadjuvant treatment, pancreas cancer, borderline resectable pancreatic

Pancreatic cancer is one of the most lethal malignancies among all types of solid tumors. Most of the patients are diagnosed at clinical and radiological late stages when curative

**Neoadjuvant Treatment for Nonmetastatic Pancreatic** 

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.75739

Christian Caglevic Medina, Sergio Panay Serra, Carlos Gallardo Araneda A, Jaime Anabalon Toha,

Sergio Panay Serra, Carlos Gallardo Araneda A, Jaime Anabalon Toha, Elizabeth Milla Ramirez and

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Elizabeth Milla Ramirez and Mauricio Mahave Caceres

Mauricio Mahave Caceres

**Abstract**

cancer

**1. Introduction**

Christian Caglevic Medina,

http://dx.doi.org/10.5772/intechopen.75739

**Cancer**

**Cancer**

#### **Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer**

DOI: 10.5772/intechopen.75739

Christian Caglevic Medina, Sergio Panay Serra, Carlos Gallardo Araneda A, Jaime Anabalon Toha, Elizabeth Milla Ramirez and Mauricio Mahave Caceres Christian Caglevic Medina, Sergio Panay Serra, Carlos Gallardo Araneda A, Jaime Anabalon Toha, Elizabeth Milla Ramirez and Mauricio Mahave Caceres

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.75739

#### **Abstract**

Pancreatic adenocarcinoma is one of the most lethal malignancies among solid tumors. Unfortunately, several patients are diagnosed at metastatic stage or with unresectable disease due to vascular compromise involving the pancreas without any chance of curative treatment. There are also two other groups of patients: resectable patients at upfront diagnosis and "borderline resectable" pancreatic cancer patients. This last group represents those patients where surgery is not always possible without a preoperative treatment allowing surgeons to perform an R0 resection. Achieving an R0 resection is the only curative option for pancreatic cancer patients; nevertheless, many R0-resected patients will relapse within 2 years from surgery. Despite adjuvant treatment, reported median overall survival is only 28 months for patients with resectable pancreatic adenocarcinoma; thus, neoadjuvant treatment has been explored in order to improve survival. We aim to describe the controversial reported data and to show the recommendations that are suggested for these patients; however, we need to remark that there is no strong data that support neoadjuvant treatment. Currently, clinical trials are ongoing, and probably soon this approach will become a standard of care among borderline resectable patients and probably in selected resectable patients too.

**Keywords:** neoadjuvant treatment, pancreas cancer, borderline resectable pancreatic cancer

#### **1. Introduction**

Pancreatic cancer is one of the most lethal malignancies among all types of solid tumors. Most of the patients are diagnosed at clinical and radiological late stages when curative

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

treatments are no feasible to perform. To date, surgical resection is still the only potential curative treatment for the adenocarcinoma of the pancreas; however, only 15–20% of all the newly diagnosed patients will be candidates for curative pancreatectomy as an upfront treatment.

mortality rate for pancreatic adenocarcinoma was 5.8 for 100,000 in men and 5.6 for 100,000 in women by 2012. Curiously, due to problems with the cancer registries in Chile as in other countries of the region, the reported mortality may be higher than the reported incidence for this malignancy during the same period [5]. Despite the lack of better cancer registries, it is well known that the incidence and mortality rates are similar among patients with pancreatic cancer, and both curves get closer in low- and middle-income countries; nevertheless, in developed countries, the chance of surviving a pancreatic cancer is still low and the incidence

Neoadjuvant Treatment for Nonmetastatic Pancreatic Cancer

http://dx.doi.org/10.5772/intechopen.75739

181

Assuming a correct diagnosis and a complete staging, there are different rates of mortality among pancreatic cancer patients according to the extension and probability of resection of the whole tumor. The 5-year survival for all the patients is 7.2%. The highest survival is found in 27.1% with very localized disease, but this rate dramatically decreases up to 10.7% for regional disease, and for metastatic disease, the 5-year survival is almost anecdotic with less

Several attempts looking for driver mutations and for trying to find target therapies to control pancreatic cancer spread have been made. Unfortunately, despite all the efforts, researchers have not conducted positive results in the clinical field, or at least their impact has not been relevant. Driver mutations such as KRAS, CDKN2A, TP53, and SMAD 4 have been involved in pancreatic cancer tumorigenesis [6], but without any impact on patients' selection of treatment yet. In other side, current immunotherapies that have achieved a great impact in the treatment of malignancies such as melanoma, lung cancer, bladder cancer, and others were

It is estimated that only 4–16% of pancreatic adenocarcinoma has a family history of this disease [8], while the rest of the cases may be considered as sporadic. To have a first-degree relative with an apparently sporadic pancreatic cancer has a moderate effect on the risk to develop this disease (odds ratio (OR), 1.76; 95% confidence interval (CI), 1.19–2.61) [9]. Selective mutations that have a recognized role in ovarian and breast cancer such as BRCA2 and, in a lesser degree, BRCA1 have been associated with familial pancreas cancer [10]. As previously mentioned, there are other selected genes that may have been associated with pancreatic cancer, for example, PALB2 [11], CDKN2A [12], and SMAD4 [13]. There are also genetic syndromes linked to pancreas cancer (e.g., hereditary pancreatitis, HNPCC, familial breast cancer with BRCA2 mutations, p16 mutations, Peutz-Jeghers syndrome, ataxia telangiectasia) [14]. Routine genetic testing for patients with newly diagnosed pancreatic cancer is controversial but it could give some clinical benefit by reducing the risk of associated cancers and by identifying family members of the index case who might benefit from screening for the cancer-predisposing mutation. Nevertheless, this is not considered a standard practice by

rate is just a little higher than the mortality rate.

than 2.5% of survival patients in that space of time [3].

not able to show benefit when tested in pancreatic cancer patients [7].

**3. Molecular biology and genetics**

current guidelines [15].

A complete radiological evaluation defines three subtypes of patients: metastatic and/or unresectable patients, resectable patients, and borderline resectable patients. This last group includes patients with vascular tumor compromise that could become resectable after an adequate neoadjuvant treatment.

The prognosis of the pancreatic cancer is poor, even in those patients with resectable disease who underwent oncological surgery and adjuvant treatments if they were recommended, but also for those patients with borderline resectable disease who achieved oncological resection after neoadjuvant treatment that may include chemotherapy, radiotherapy, or a combination of both. Despite an optimal treatment, many of the resected patients will relapse within the 24 months after completing adjuvant treatment or after surgery. The 5-year survival following pancreaticoduodenectomy is only 25–30% for node-negative and 10% for node-positive tumors. The need to improve these results has led us to the development of new treatment strategies that will be discussed ahead in this chapter.
