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The survival impact of palliative radiotherapy on synchronous metastatic pancreatic ductal adenocarcinoma: metastatic site can serve for radiotherapy-decision.

ABSTRACT: Background: The metastatic site seems to represent a malignancy with a different biological characteristic and is an important prognostic factor in metastatic pancreatic ductal adenocarcinoma (mPDAC). Palliative radiotherapy is a therapeutic option, and usually used for pain management in the treatment of mPDAC. The real-world effect of radiotherapy on the survival outcomes of mPDAC patients might do exist and is worth exploring. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) was extracted to identify mPDAC diagnosed in the periods of 2010-2016. The statistical methods included Pearson's chi-square test, Log-rank test, Cox regression model and propensity score matching (PSM). Results: Radiotherapy was able to improve the overall survival of PDAC with liver metastasis (p<0.001), but not for PDAC patients with lung (p=0.130), bone (p=0.451) and brain metastasis (p=0.226) before PSM. Radiotherapy can only a prognostic factor for PDAC liver metastasis (p=0.001) in the cox regression analysis. The survival curves provided consistent results with cox regression analysis (PDAC with liver metastasis: p=0.023, PDAC with lung metastasis: p=0.528, PDAC with bone metastasis: p=0.210, PDAC with brain metastasis: p=0.106) after PSM. We continue to divided PDAC liver patients into PDAC-liver-metastasis with and without lung, bone, and/or brain (LBB) metastasis. Finally, radiotherapy can be used as a feasible treatment to prolong the overall survival of patients with PDAC liver metastasis without LBB metastasis. Conclusions: Radiotherapy can be used as a feasible treatment to prolong the overall survival of patients with PDAC liver metastasis without LBB metastasis.

SUBMITTER: Xu B

PROVIDER: S-EPMC8771529 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC. METHODS:PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS. Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods. RESULTS:Before PSM analysis, the OS of surgery plus chemotherapy (HRs?=?0.896, 95%CIs, 0.827-0.970; P?=?0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N?+?M0 patients, adjuvant radiotherapy (HRs?=?0.613, 95% CIs, 0.579-0.649; P?<?0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs?=?0.482, 95% CIs, 0.347-0.670; P?<?0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N?+?M0 patients, neoadjuvant radiotherapy (HRs?=?0.338, 95% CIs, 0.215-0.532; P?<?0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy. Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N?+?M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients. CONCLUSIONS:For patients with non-metastatic PDAC, neoadjuvant radiotherapy, adjuvant radiotherapy and surgery plus chemotherapy were superior to only surgery in OS. For patients with stage T4 non-metastatic PDAC, neoadjuvant radiotherapy had the potential to be strongly recommended over adjuvant radiotherapy and surgery plus chemotherapy. However, neoadjuvant radiotherapy failed to benefit the survival of T1-3N0M0 stage patients, and surgery plus chemotherapy was preferred. For T1-3N?+?M0, neoadjuvant radiotherapy had no obvious advantage over adjuvant radiotherapy or surgery plus chemotherapy in OS, and adjuvant radiotherapy was more recommended.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at an advanced stage, with systemic therapy being the mainstay of treatment. Survival continues to be limited, typically less than 1 year. The PDAC microenvironment is characterized by a paucity of malignant epithelial cells, abundant stroma with predominantly immunosuppressive T cells and myelosuppressive-type macrophages (M2), and hypovascularity. The current treatment options for metastatic PDAC are modified (m)FOLFIRINOX /FOLFIRINOX or nab-paclitaxel and gemcitabine in patients with good performance status (PS) (ECOG 0-1/KPS 70-100%) and gemcitabine with or without a second agent for those with ECOG PS 2-3. New therapies are emerging, and the current guidelines endorse both germline and somatic testing in PDAC to evaluate actionable findings. Important themes related to new therapeutic approaches include DNA damage repair strategies, immunotherapy, targeting the stroma, and cancer-cell metabolism. Targeted therapy alone (outside small genomically defined subsets) or in combination with standard cytotoxic therapy, thus far, has proven disappointing in PDAC; however, novel therapies are evolving with increased integration of genomic profiling along with a better understanding of the tumor microenvironment and immunology. A small but important sub-group of patients have some of these agents available in the clinics for use. Olaparib was recently approved by the US Food and Drug Administration for maintenance therapy in germline BRCA1/2 mutated PDAC following demonstration of survival benefit in a phase 3 trial. Pembrolizumab is approved for patients with defects in mismatch repair/microsatellite instability. PDAC with wild-type KRAS represents a unique subgroup who have enrichment of potentially targetable oncogenic drivers. Small-molecule inhibitors including ERBB inhibitors (e.g., afatinib, MCLA-128), TRK inhibitors (e.g., larotrectinib, entrectinib), ALK/ROS inhibitor (e.g., crizotinib), and BRAF/MEK inhibitors are in development. In a small subset of patients with the KRASG12C mutation, a KRASG12C inhibitor, AMG510, and other agents are being investigated. Major efforts are underway to effectively target the tumor microenvironment and to integrate immunotherapy into the treatment of PDAC, and although thus far the impact has been modest to ineffective, nonetheless, there is optimism that some of the challenges will be overcome.

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The survival impact of palliative radiotherapy on synchronous metastatic pancreatic ductal adenocarcinoma: metastatic site can serve for radiotherapy-decision.

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