Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Tempero, Margaret A.; Malafa, Mokenge P.; Al-Hawary, Mahmoud M.; Behrman, Stephen W.; Benson, Al B.; Cardin, Dana Backlund; Chiorean, E. Gabriela; Chung, Vincent; Czito, Brian G.; Chiaro, Marco Del; Dillhoff, Mary; Donahue, Timothy R.; Dotan, Efrat; Ferrone, Cristina R.; Fountzilas, Christos; Hardacre, Jeffrey M.; Hawkins, William G.; Klute, Kelsey; Ko, Andrew H.; Kunstman, John W.; LoConte, Noelle K.; Lowy, Andrew M.; Moravek, Cassadie; Nakakura, Eric K.; Narang, Amol; Obando, Jorge; Polanco, Patricio M.; Reddy, Sushanth; Reyngold, Marsha; Scaife, Courtney L.; Shen, Jeanne; Vollmer, Charles M.; Wolff, Robert A.; Wolpin, Brian M.; Lynn, Beth; George, Giby V.

doi:10.6004/jnccn.2021.0017

Cited by 621 publications

(476 citation statements)

References 211 publications

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“…Currently, the diagnostic work-up of suspected pancreatic lesions is ce-CT. Current guidelines are indifferent on the role and diagnostic value of FDG-PET/CT [ 8 ]; however, this might change in the future based on recent literature as discussed in Section 4.2 . Furthermore, with the implementation of neoadjuvant treatment schedules as standard of care for borderline resectable tumors, accurate treatment response monitoring and determination of resectability is important.…”

Section: Positron Emission Tomography—computed Tomography (Pet/ct)mentioning

confidence: 99%

“…The diagnostic workup for PDAC typically consists of a combination of CT for staging and endoscopic ultrasound with fine needle aspiration (EUS-FNA) or biopsy or endoscopic retrograde cholangiopancreatography (ERCP) to obtain histological confirmation of disease [ 8 , 9 ]. Recently, magnetic resonance imaging (MRI) has gained ground for the primary evaluation of local disease stage and vascular encasement by tumor tissue, as well as the characterization of distant metastases, especially in the peritoneal cavity and liver [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…The role of 18 F-FDG positron emission tomography (PET) combined with computed tomography (PET/CT) in the workup of pancreatic cancer remains controversial. The National Comprehensive Cancer Network (NCCN) consensus guideline states that FDG-PET/CT may be used per institutional preference; although, it is not a substitute for high-quality contrast-enhanced CT (ce-CT) [ 8 ]. The European Society for Medical Oncology (ESMO) states likewise and says the role of PET/CT should be further clarified [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Aiming to increase the number of patients eligible for curative-intent resection and to further optimize surgical outcome, the combination of neoadjuvant induction therapy and adjuvant treatment has been under clinical investigation in the past years [ 4 , 17 , 18 , 19 , 20 ]. There are currently two combinations recommended as first-line (neo)adjuvant treatment regimens by the NCCN and ESMO: (modified) FOLFIRINOX (Folic acid, 5-Fluoruracil, Irinotecan, and Oxaliplatin) or gemcitabine plus nab-paclitaxel, the last is often combined with radiation therapy [ 8 , 9 , 21 ]. Since individual patient health status and morbidity highly influence the ability to receive (neo)adjuvant treatment, most well-considered multidisciplinary recommendations for duration and intensity of treatment are made within these standardized regimens or ongoing clinical trials for individual patients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

Cancers

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Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient’s treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.

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Section: Positron Emission Tomography—computed Tomography (Pet/ct)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Dam

Vuijk

Stibbe

et al. 2021

Cancers

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“…Over the past decade, poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been investigated extensively in solid tumors and approved for use in subsets of patients with ovarian, breast, prostate, and pancreatic cancer [ 1 , 2 , 3 , 4 , 5 , 6 ]. These agents are especially active in cells with impaired ability to repair DNA double-strand breaks (DSBs) through the homologous recombination (HR) pathway, a high-fidelity repair pathway that is operative in the S and G2 phases of the cell cycle [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword

Csizmar

Saliba

Swisher

et al. 2021

Cancers

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Despite recent discoveries and therapeutic advances in aggressive myeloid neoplasms, there remains a pressing need for improved therapies. For instance, in acute myeloid leukemia (AML), while most patients achieve a complete remission with conventional chemotherapy or the combination of a hypomethylating agent and venetoclax, de novo or acquired drug resistance often presents an insurmountable challenge, especially in older patients. Poly(ADP-ribose) polymerase (PARP) enzymes, PARP1 and PARP2, are involved in detecting DNA damage and repairing it through multiple pathways, including base excision repair, single-strand break repair, and double-strand break repair. In the context of AML, PARP inhibitors (PARPi) could potentially exploit the frequently dysfunctional DNA repair pathways that, similar to deficiencies in homologous recombination in BRCA-mutant disease, set the stage for cell killing. PARPi appear to be especially effective in AML with certain gene rearrangements and molecular characteristics (RUNX1-RUNX1T1 and PML-RARA fusions, FLT3- and IDH1-mutated). In addition, PARPi can enhance the efficacy of other agents, particularly alkylating agents, TOP1 poisons, and hypomethylating agents, that induce lesions ordinarily repaired via PARP1-dependent mechanisms. Conversely, emerging reports suggest that long-term treatment with PARPi for solid tumors is associated with an increased incidence of myelodysplastic syndrome (MDS) and AML. Here, we (i) review the pre-clinical and clinical data on the role of PARPi, specifically olaparib, talazoparib, and veliparib, in aggressive myeloid neoplasms and (ii) discuss the reported risk of MDS/AML with PARPi, especially as the indications for PARPi use expand to include patients with potentially curable cancer.

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Comparative Outcomes of First-Line Chemotherapy for Metastatic Pancreatic Cancer Among the Regimens Used in Japan

et al. 2022

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IMPORTANCE Various first-line chemotherapy treatment regimens for patients with metastatic pancreatic cancer have been approved in Japan, including gemcitabine (GEM); fluorouracil, leucovorin, irinotecan, and oxaliplatin combination (FOLFIRINOX); GEM plus albumin-bound paclitaxel (GEM+NPTX), and S-1 (tegafur + gimeracil + oteracil). However, direct comparisons of these chemotherapy regimens are limited. OBJECTIVETo assess the short-term and long-term outcomes associated with first-line chemotherapy regimens for metastatic pancreatic cancer compared with chemotherapy regimens recommended in Japanese guidelines. DATA SOURCES In this systematic review and network meta-analysis, the bibliographic databases PubMed, Cochrane Library, and Web of Science, as well as medical journals published between January 1, 2002, and December 31, 2018, were searched for clinical trials comparing chemotherapy regimens. STUDY SELECTION Randomized 2-arm clinical trials evaluating first-line chemotherapy for advanced or metastatic pancreatic cancer were included. DATA EXTRACTION AND SYNTHESIS The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Extension Statement for Reporting of Systematic Reviews IncorporatingNetwork Meta-analyses of Health Care Interventions was followed for data abstractions. Data were pooled using a random-effects model. The SIGN 50 Quality Assessment Instrument was used to assess the risk of bias and overall study quality of the selected trials. MAIN OUTCOMES AND MEASURESThe primary end point was overall survival (OS), and the secondary end point was progression-free survival (PFS) compared with GEM for first-line chemotherapy for metastatic pancreatic cancer. The Kaplan-Meier curve of GEM from the literature and the estimated hazard ratios (HRs) were used to model the long-term associations to calculate the area under the curve (AUC) (person-months) for OS and PFS of each chemotherapy. Sensitivity analyses with multiple functional models were conducted to confirm the long-term estimations. RESULTS A total of 22 regimens (25 studies) for OS and a total of 18 regimens (21 studies) for PFS were identified from literature. The total number of participants was 10 186, with 5856 male (57.5%) and 4330 female (42.5%). The FOLFIRINOX and GEM+NPTX regimens were associated with reduction in the risk of death, with an HR of 0.57 (95% CI, 0.41-0.79) and 0.72 (95% CI, 0.55-0.95) compared with GEM, respectively. The curve estimation also showed that FOLFIRINOX had the largest AUC for survival at 15.49 person-months (range, 13.84-15.51 person-months), followed by (continued) Key Points Question What are the comparative short-term and long-term outcomes associated with first-line chemotherapy regimens for patients with metastatic pancreatic cancer, and how do they compare with chemotherapy regimens recommended in Japanese guidelines? Findings In this systematic review and network meta-analysis of 25 randomized clinical trials assessing firstline chemotherapy regimens for advanced or metastatic pancreati...

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Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Cited by 621 publications

References 211 publications

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

Overview and Future Perspectives on Tumor-Targeted Positron Emission Tomography and Fluorescence Imaging of Pancreatic Cancer in the Era of Neoadjuvant Therapy

PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword

Comparative Outcomes of First-Line Chemotherapy for Metastatic Pancreatic Cancer Among the Regimens Used in Japan

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