History of preoperative therapy for pancreatic cancer and the MD Anderson experience

BackgroundThe choice between upfront surgery or neoadjuvant treatments (NAT) for resectable pancreatic ductal adenocarcinoma (R-PDAC) is controversial. R-PDAC with potential nodal involvement could benefit from NT. Ca (Carbohydrate antigen) 19.9 and serum albumin levels, alone or in combination, have proven their efficacy in assessing PDAC prognosis. The objective of this study was to evaluate the role of Ca 19.9 serum levels in predicting nodal status in R-PDAC.MethodsPreoperative Ca 19.9, as well as serum albumin levels, of 165 patients selected for upfront surgery have been retrospectively collected and correlated to pathological nodal status (N), resection margins status (R) and vascular resections (VR). We further performed ROC curve analysis to identify optimal Ca 19.9 cut-off for pN+, R+ and vascular resection prediction.ResultsIncreased Ca 19.9 levels in 114 PDAC patients were significantly associated with pN+ (p <0.001). This ability, confirmed in all the series by ROC curve analysis (Ca 19.9 ≥32 U/ml), was lost in the presence of hypoalbuminemia. Furthermore, Ca 19.9 at the cut off >418 U/ml was significantly associated with R+ (87% specificity, 36% sensitivity, p 0.014). Ca 19.9, at the cut-off >78 U/ml, indicated a significant trend to predict the need for VR (sensitivity 67%, specificity 53%; p = 0.059).ConclusionsIn R-PDAC with normal serum albumin levels, Ca 19.9 predicts pN+ and R+, thus suggesting a crucial role in deciding on NAT.

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“…As reported by Gaskill, NAT can result in the patient losing "the window for surgical cure" (17).…”

Section: Introductionmentioning

confidence: 92%

CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis

et al. 2021

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“…If metastatic disease is detected at diagnostic laparoscopy, patients can avoid the more morbid exploratory laparotomy, experience a more rapid postoperative recovery, and initiate systemic chemotherapy earlier [ 43 , 44 , 45 ]. Many high-volume institutions, including several NCCN member institutions, routinely employ diagnostic laparoscopy before formal resection to confirm the absence of metastatic disease [ 27 , 46 ].…”

Section: Determination Of Resectabilitymentioning

confidence: 99%

Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma

Jain,

Maxwell,

Katz

et al. 2023

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.

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“…Additionally, neoadjuvant-based systemic chemotherapy has also been an important mode of treatment for solid tumours and also for pancreatic cancer, promoting patient survival (92,93). Evidence in breast cancer and osteosarcoma shows that neoadjuvants suppress autophagy and increase drug sensitivity of the malignant cells.…”

Section: Effect Onmentioning

confidence: 99%

Noncoding RNAs as key modulators of autophagy in pancreatic cancer (Review)

et al. 2021

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Inability of early detection as well as lack of proper therapeutic intervention, both add to the complexity of pancreatic cancer. Understanding of the basic cellular processes is of the utmost importance and autophagy is one of these processes. Considering the importance of this process in normal cellular functions as well as in pathological states, elaboration of the updated information on the mechanism of autophagy was initially carried out. Autophagy is a process for degradation of damaged cellular organelles, abnormal proteins and even nutrients which happen via formation of autophagosomes. Incidentally, autophagy has been shown to play both oncogenic and tumour-suppressive functions in cancer and has also been shown to modulate stemness of cancer cells, recurrence and resistance to chemotherapeutic agents. The contribution of autophagy genes and pathways in pancreatic tumorigenesis was also evaluated. Regulation is the key step in any such cellular phenomenon and noncoding RNA-mediated regulation is an emerging field. While miRNAs participate mainly in post-transcriptional regulation, long noncoding RNAs and circular RNAs have more diverse regulatory functions. Noncoding RNAs are also shown to modulate both the tumour-promoting and tumour-suppressing functions of autophagy in pancreatic cancer. The implication of noncoding RNA-mediated regulation with respect to radio-resistance and chemo-resistance of pancreatic cancer cells was also assessed. To the best of our knowledge, this is the first ever attempt trying to decipher the cross-talk between autophagy-noncoding RNAs and genes involved in the development and progression of pancreatic cancer. Contents 1. Introduction 2. Mechanism of autophagy 3. Autophagy and cancer 4. Autophagy and pancreatic cancer 5. Noncoding RNAs: Key regulatory module of autophagy 6. Conclusion and future direction

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History of preoperative therapy for pancreatic cancer and the MD Anderson experience

Cited by 4 publications

References 70 publications

CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis

CA19.9 Serum Level Predicts Lymph-Nodes Status in Resectable Pancreatic Ductal Adenocarcinoma: A Retrospective Single-Center Analysis

Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma

Noncoding RNAs as key modulators of autophagy in pancreatic cancer (Review)

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