Advances and Remaining Challenges in the Treatment for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Sulciner, Megan L.; Ashley, Stanley W.; Molina, George

doi:10.3390/jcm11164866

Cited by 2 publications

(2 citation statements)

References 44 publications

(69 reference statements)

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“…NAT for borderline resectable and locally advanced PDAC has been associated with overall survival benefit, which could be due to downstaging of disease and greater likelihood of achieving complete resection [ 30 ]. However, tumor recurrence or metastasis occurs in majority of the cases within 1–2 years of surgery, and the median overall survival is only 20–25 months after surgery [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19–9

Yoo,

Lee,

Joo

et al. 2023

Cancer Imaging

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Background CT prediction of resectability and prognosis following neoadjuvant treatment (NAT) in patients with pancreatic ductal adenocarcinoma (PDAC) remains challenging. This study aims to determine whether addition of 18F-fluorodeoxyglucose (FDG) postiron emission tomography (PET)/MRI and carbohydrate antigen (CA) 19–9 to contrast-enhanced CT (CECT) can improve accuracy of predicting resectability compared to CECT alone and predict prognosis in PDAC patients after NAT. Methods In this retrospective study, 120 PDAC patients (65 women; mean age, 66.7 years [standard deviation, 8.4]) underwent CECT, PET/MRI, and CA 19–9 examinations after NAT between January 2013 and June 2021. Three board-certified radiologists independently rated the overall resectability on a 5-point scale (score 5, definitely resectable) in three sessions (session 1, CECT; 2, CECT plus PET/MRI─no FDG avidity and no diffusion restriction at tumor-vessel contact indicated modification of CECT scores to ≥ 3; 3, CECT plus PET plus CA 19–9─no FDG avidity at tumor-vessel contact and normalized CA 19–9 indicated modification of CECT scores to ≥ 3). Jackknife free-response receiver operating characteristic method and generalized estimating equations were used to compare pooled area under the curve (AUC), sensitivity, and specificity of three sessions. Predictors for recurrence-free survival (RFS) were assessed using Cox regression analyses. Results Each session showed different pooled AUC (session 1 vs. 2 vs. 3, 0.853 vs. 0.873 vs. 0.874, p = 0.026), sensitivity (66.2% [137/207] vs. 86.0% [178/207] vs. 84.5% [175/207], p < 0.001) and specificity (67.3% [103/153] vs. 58.8% [90/153] vs. 60.1% [92/153], p = 0.048). According to pairwise comparison, specificity of CECT plus PET/MRI was lower than that of CECT alone (adjusted p = 0.042), while there was no significant difference in specificity between CECT alone and CECT plus PET plus CA 19–9 (adjusted p = 0.081). Twenty-eight of 69 patients (40.6%) with R0 resection experienced tumor recurrence (mean follow-up, 18.0 months). FDG avidity at tumor-vessel contact on post-NAT PET (HR = 4.37, p = 0.033) and pathologically confirmed vascular invasion (HR = 5.36, p = 0.004) predicted RFS. Conclusion Combination of CECT, PET and CA 19–9 increased area under the curve and sensitivity for determining resectability, compared to CECT alone, without compromising the specificity. Furthermore, 18F-FDG avidity at tumor-vessel contact on post-NAT PET predicted RFS.

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Section: Discussionmentioning

confidence: 99%

Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19–9

Yoo,

Lee,

Joo

et al. 2023

Cancer Imaging

View full text Add to dashboard Cite

show abstract

“…Although PDAC is not a common solid cancer and represents only approximately 3% of newly diagnosed cancer cases each year, it has been considered the leading cause of cancer-related death within the last 10 years [ 2 ]. Due to its features of rapid progression and radiochemoresistance, the five-year survival rate of PDAC is less than 15% [ 3 ]. Currently, paclitaxel and gemcitabine-based chemotherapy is the standard of care for PDAC treatment, and there is no effective targeted therapeutic approach against PDAC [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

Bu¹,

Zhao²,

Wang³

et al. 2023

Oncology Research

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Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. Poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer, opening a new era for targeted therapy for this disease. However, most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors. Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. Moreover, we found that knockdown of the mTORC2 obligate subunit Rictor sensitized pancreatic cancer cells to the PARP inhibitor olaparib. Mechanistically, we showed that mTORC2 positively regulates homologous recombination (HR) repair by modulating BRCA1 recruitment to DNA double-strand breaks (DSBs). In addition, we confirmed that combination treatment with the mTORC2 inhibitor PP242 and the PARP inhibitor olaparib synergistically inhibited pancreatic cancer growth in vivo . Thus, this study provides a novel target and strategy for optimizing PARP inhibitor efficiency in pancreatic cancers.

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Advances and Remaining Challenges in the Treatment for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Cited by 2 publications

References 44 publications

Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19–9

Post-neoadjuvant treatment pancreatic cancer resectability and outcome prediction using CT, 18F-FDG PET/MRI and CA 19–9

mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance

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