Are We Sure that Adjuvant Chemotherapy is the Best Approach for Resectable Pancreatic Cancer? Are We in the Era of Neoadjuvant Treatment? A Review of Current Literature

Oneda, Ester; Zaniboni, Alberto

doi:10.3390/jcm8111922

Cited by 28 publications

(19 citation statements)

References 75 publications

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“…However, the slow development of new chemotherapeutic agents seriously restrained the improvement of long-term survival in mPC patients. During the past decades, most chemotherapy regimens have always been based on 5-fluorouracil and gemcitabine [16]. The emergence of molecule-targeted drugs did not even bring encouraging clinical benefits [17][18][19].…”

Section: Discussionmentioning

confidence: 99%

Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs

Fěng¹,

Cai

Wang

et al. 2020

BMC Gastroenterol

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Background: With the improvement of treatment and prognosis for patients with late malignant diseases, certain malignancies with distant metastasis (M1 category) have been further classified into M1a (single metastatic site) and M1b (multiple metastatic sites) category in the staging system. We aimed to assess the feasibility of sub-classifying metastatic pancreatic adenocarcinoma (mPA) into M1a and M1b category depending on the number of metastatic organs. Methods: Patient records were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). Univariable and multivariable analyses were performed using the Cox regression model. Then survival analysis was determined using the Kaplan-Meier method. Results: A total of 11,885 patients were included in this analysis, including 9425 patients with single metastasis and 2460 patients with multiple metastases. Multivariable analysis showed that gender, age, marital status, grade, surgery, chemotherapy, and radiotherapy were independent prognostic factors for patients with single metastasis; gender, age, marital status, grade, chemotherapy and radiotherapy were independent prognostic factors for patients with multiple metastases. Notably, surgery was an independent prognostic factor for patients with single metastasis (P < 0.001) but not for patients with multiple metastases (P = 0.134). Kaplan-Meier analysis showed that patients with single metastasis (M1a) had better survival outcomes than patients with multiple metastases (M1b) (P < 0.001). Conclusions: PA patients with M1 diseases could be divided into M1a (single metastasis) category and M1b (multiple metastases) category by the number of metastatic organs. The subclassification would facilitate individualized treatment for late PA patients. Surgery was associated with lower mortality in M1a patients but not significantly in M1b patients.

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Section: Discussionmentioning

confidence: 99%

Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs

Fěng¹,

Cai

Wang

et al. 2020

BMC Gastroenterol

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“…The main weakness of published studies is the lack of statistical power and the heterogenous populations (for example, the pooling of resectable, borderline and locally advanced tumors). In addition, these studies are limited by the small populations, low-volume centers and lack of consensus on resectability criteria after induction chemotherapy [28,33] underwent surgery in the experimental arm (seven had R0 resection status, nine had R1).…”

Section: A Induction Strategymentioning

confidence: 99%

“…Up to 30% of patients do not receive adjuvant therapy[28] (Oneda 2019). Modified FOLFIRINOX cannot be administered if patients have not fully recovered from major surgery in the presence of fatigue, weight loss, denutrition or diarrhea.…”

mentioning

confidence: 99%

Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021

Turpin¹,

Amrani²,

Bachet³

et al. 2020

Preprint

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Adjuvant chemotherapy is currently used in all patients with resected pancreatic cancer who are able to begin treatment within 3 months after surgery. Since the recent publication of the PRODIGE 24 trial results, modified FOLFIRINOX has become the standard-of-care in the non-Asian population with localized pancreatic adenocarcinoma following surgery. Nevertheless, there is still a risk of toxicity, and feasibility may be limited in heavily pre-treated patients. In more frail patients, gemcitabine-based chemotherapy remains a suitable option, for example gemcitabine or 5FU in monotherapy. In Asia, although S1-based chemotherapy is the standard of care it is not readily available outside Asia and data are lacking in non-Asiatic patients. In patients in whom resection is not initially possible, intensified schemes such as FOLFIRINOX or Gemcitabine-Nabpaclitaxel have been confirmed as options to enhance the response rate and resectability, promoting research in adjuvant therapy. In particular, should oncologists prescribe adjuvant treatment after a long sequence of chemotherapy +/- chemoradiotherapy and surgery? Should oncologists consider the response rate, the R0 resection rate alone, or the initial chemotherapy regimen? And finally, should they take into consideration the duration of the entire sequence, or the presence of limited toxicities of induction treatment? The aim of this review is to summarize adjuvant management of resected pancreatic cancer and to raise current and future concerns, especially the need for biomarkers and the best holistic care for patients.

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“…Currently, gemcitabine (GEM) chemotherapy remains the most important clinical treatment. 3,4 Because of acquired drug resistance, PC patients have a poor prognosis. Therefore, the molecular mechanism of GEM-resistance needs to be studied further in PC.…”

Section: Introductionmentioning

confidence: 99%

<p>CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1</p>

Liu¹,

Li²,

Luo³

et al. 2020

CMAR

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Background: Pancreatic cancer is one of the most common malignant diseases in the world. Gemcitabine chemotherapy remains the most important clinical treatment. However, research found that pancreatic cancer cells have chemoresistance to gemcitabine and the effect is not satisfactory. Therefore, it is urgent to find an effective early diagnosis and treatment strategy. Circular RNA is one of the most popular prognostic biomarkers in GEM-resistant PC. Materials and Methods: The present study was designed to evaluate the role of circHIPK3 in PC. The expression of circHIPK3 in PC tissues and cells and its effect on proliferation, migration, invasion, EMT, and apoptosis were investigated in vitro; its effect on tumor xenografts was assessed in vivo. Used bioinformation analysis to predict which miRNAs could potentially interact with circHIPK3, mRNA, and miR-330-5p. Results: RT-PCR showed that the level of circHIPK3 was increased in PC tumor tissues; moreover, circHIPK3 was also increased in GEM-resistant PC tumors tissues and GEMresistant PC cells. Sh-circHIPK3 could knockdown circHIPK3 in PANC-1-GEM and SW-1990-GEM and could significantly inhibit cell proliferation, invasion, migration, EMT and enhance cell apoptosis, compare with control group, the tumor xenografts of circHIPK3 knockdown group were significantly smaller. CircHIPK3 served as a sponge for miR-330-5p, and miR-330-5p directly bound to the 3′ UTR of RASSF1 were revealed by dual luciferase assay and RIP in PC cells. CircHIPK3 knockdown of RASSF1 expression could neutralize the cytological function of PC cells by miR-330-5p inhibitor mediated GEM-resistance. Conclusion: CircHIPK3 promotes gemcitabine (GEM) resistance in pancreatic cancer cells by targeting RASSF1 via miR-330-5p and regulates proliferation, invasive, migration, EMT, and apoptosis. Our research revealed that circHIPK3 may be a novel biomarker in GEMresistant PC and could be used as a prognostic target.

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Are We Sure that Adjuvant Chemotherapy is the Best Approach for Resectable Pancreatic Cancer? Are We in the Era of Neoadjuvant Treatment? A Review of Current Literature

Cited by 28 publications

References 75 publications

Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs

Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs

Adjuvant Pancreatic Cancer Management: Towards New Perspectives in 2021

<p>CircHIPK3 Promotes Gemcitabine (GEM) Resistance in Pancreatic Cancer Cells by Sponging miR-330-5p and Targets RASSF1</p>

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