Surgery After Response to Chemotherapy for Locally Advanced Pancreatic Ductal Adenocarcinoma: A Guide for Management

Fong, Zhi Ven; Ferrone, Cristina R.

doi:10.6004/jnccn.2021.7009

Cited by 8 publications

(7 citation statements)

References 57 publications

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“…Determining the optimal response to initial induction chemotherapy in BR/LA PDAC presents a therapeutic dilemma. A multidisciplinary team needs to determine whether chemotherapeutic benefit has been maximized and either proceed to chemoradiation 2 and/or surgery, 32 extend the duration of the same chemotherapeutic regimen, or consider a chemotherapeutic switch. 33 Having highly predictive preoperative data is critical for decisionmaking, with a substantial influence on patient outcomes.…”

Section: Discussionmentioning

confidence: 99%

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma

Abdelrahman

Goenka

Alva-Ruiz

et al. 2022

Journal of the National Comprehensive Cancer Network

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Background: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. Methods: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). Results: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P<.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13–0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P<.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9–153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2–0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1–0.4). Conclusions: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.

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Section: Discussionmentioning

confidence: 99%

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma

Abdelrahman

Goenka

Alva-Ruiz

et al. 2022

Journal of the National Comprehensive Cancer Network

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“…Due to the insidious and aggressive nature of PAAD, it is difficult to detect and prevent PAAD at an early stage. At the time of consultation, approximately 80% of patients have locally advanced or metastatic cancer [ 30 ]. Although multimodal therapy has been improved, surgery remains an effective therapeutic strategy for this disease.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes

Yang

Wei

et al. 2022

Cancer Cell Int

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Background Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD. Methods RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by “limma_3.42.2” package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays. Results The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes. Conclusions We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.

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“…Albumin-bound paclitaxel (nab-paclitaxel, Abraxane ® , Celgene Corporation, Summit, NJ, USA) is used as a first-line treatment of PDAC. Nab-paclitaxel is delivered in combination with gemcitabine and is regularly used as a neoadjuvant treatment for pre-surgical and metastatic PDAC patients [48]. Elevated FcRn may increase nab-paclitaxel internalization in tumor associated macrophages which was recently shown to be important for its anti-PDAC efficacy [49].…”

Section: Discussionmentioning

confidence: 99%

The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer

Thomas

Torok

Agrawal

et al. 2022

IJMS

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The neonatal Fc receptor (FcRn) is responsible for recycling of IgG antibodies and albumin throughout the body. This mechanism has been exploited for pharmaceutic delivery across an array of diseases to either enhance or diminish this function. Monoclonal antibodies and albumin-bound nanoparticles are examples of FcRn-dependent anti-cancer therapeutics. Despite its importance in drug delivery, little is known about FcRn expression in circulating immune cells. Through time-of-flight mass cytometry (CyTOF) we were able to characterize FcRn expression in peripheral blood mononuclear cell (PBMC) populations of pancreatic ductal adenocarcinoma (PDAC) patients and non-cancer donors. Furthermore, we were able to replicate these findings in an orthotopic murine model of PDAC. Altogether, we found that in both patients and mice with PDAC, FcRn was elevated in migratory and resident classical dendritic cell type 2 (cDC2) as well as monocytic and granulocytic myeloid-derived suppressor cell (MDSC) populations compared to tumor-free controls. Furthermore, PBMCs from PDAC patients had elevated monocyte, dendritic cells and MDSCs relative to non-cancer donor PBMCs. Future investigations into FcRn activity may further elucidate possible mechanisms of poor efficacy of antibody immunotherapies in patients with PDAC.

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Surgery After Response to Chemotherapy for Locally Advanced Pancreatic Ductal Adenocarcinoma: A Guide for Management

Cited by 8 publications

References 57 publications

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma

Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes

The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer

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