Moving the Needle on Precision Medicine in Pancreatic Cancer

O’Kane, Grainne M.; Lowery, Maeve A.

doi:10.1200/jco.21.02514

Cited by 22 publications

(14 citation statements)

References 86 publications

(115 reference statements)

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“…In this sense, we certainly hope to validate externally our results in a new prospective and broader study. Finally, and although several molecular test approaches are highly recommended in the metastatic PDAC setting from the outset [ 47 ] there is a tremendous gap in these less advanced stages.…”

Section: Discussionmentioning

confidence: 99%

Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma

González-Borja

Viúdez

Alors‐Perez

et al. 2022

Cancers

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Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CKβ8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.

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Section: Discussionmentioning

confidence: 99%

Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma

González-Borja

Viúdez

Alors‐Perez

et al. 2022

Cancers

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“…In distinction to PDAC which is associated with KRAS driver mutations in more than 93% of cases, KRAS mutations occur at a much lower prevalence in the acinar/mixed neuroendocrine tumor (9%)[ 18 - 21 ]. While it is difficult to generalize as pancreatic carcinoma is a complex heterogeneous disease, a strong argument can be made that the lack of mutated KRAS identifies a cohort rich in targetable alterations including fusions, and should have access to integrative germline and somatic sequencing[ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Germline testing and tumor sequencing results are invaluable in identifying PACC patients for treatment regime determination and predictive biomarkers for investigational targeted therapies[ 14 , 22 , 23 , 26 , 27 ]. Newly diagnosed patients with PACC should undergo germline genetic testing and somatic profiling where appropriate, given the high frequency of pathogenic germline BRCA alterations in PACC.…”

Section: Discussionmentioning

confidence: 99%

Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

Lee¹,

Holter²,

Borgida³

et al. 2022

World J Gastroenterol

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BACKGROUND Pancreatic acinar cell carcinoma (PACC) is a rare tumor. Up to 45% of PACCs have alterations in the DNA damage repair pathway and 23% harbor rearrangements in the BRAF or RAF1 genes. We present a PACC case with a germline BRCA2 likely pathogenic variant (LPV) to highlight the impact of genomic testing on treatment decisions and patient outcomes. In our larger case series, we provide clinic-based information on additional 10 PACC patients treated in our center. CASE SUMMARY A 70-year-old male was diagnosed with advanced PACC. At presentation, he was cachectic with severe arthralgia despite prednisolone and a skin rash that was later confirmed to be panniculitis. He was treated with modified FOLFIRINOX (mFFX) with the knowledge of the germline BRCA2 LPV. Following 11 cycles of mFFX, a computed tomography (CT) scan demonstrated significant tumor response in the pancreatic primary and hepatic metastases, totaling 70% from baseline as per Response Evaluation Criteria in Solid Tumors. Resolution of the skin panniculitis was also noted. We identified two additional PACCs with druggable targets in our case series. Our data contribute to practical evidence for the value of germline and somatic profiling in the management of rare diseases like PACC. CONCLUSION This patient and others in our larger case series highlight the importance of genomic testing in PACC with potential utility in personalized treatment.

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“…KRAS mutation is reportedly associated with poor prognosis in patients with different cancer types [ 21 , 22 , 23 , 24 , 25 , 26 ]. However, mutational data on PHC are few and controversial.…”

Section: Discussionmentioning

confidence: 99%

The Impact of KRAS Mutational Status on Long-Term Survival following Liver Resection for Hilar Cholangiocarcinoma

Ardito

Razionale

Campisi

et al. 2022

Cancers

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KRAS mutation is reportedly associated with poor prognosis in patients with different cancer types. However, mutational data on hilar cholangiocarcinoma are few and controversial. The aim of this study was to evaluate the rate of KRAS mutations in a single-center homogeneous population resected for hilar cholangiocarcinoma and the subsequent impact on prognosis. KRAS mutation status was evaluated in 54 patients undergoing major hepatectomy combined with resection of the main biliary confluence and regional lymphadenectomy for hilar cholangiocarcinoma between 2001 and 2019. Among these 54 patients, 12 (22.2%) had a KRAS mutation. KRAS mutation was not related with pathologic characteristics of the tumor. Five-year overall survival (OS) in patients with KRAS mutation was significantly lower than that observed in patients with KRAS wild type (0 vs. 49.2%, respectively; p = 0.003). In the multivariable analysis; independent predictors of poor OS were KRAS mutation (HR = 5.384; p = 0.003) and lymph node metastases (HR = 2.805; p = 0.023). The results of our study suggested that KRAS mutation in hilar cholangiocarcinoma was not rarely observed. KRAS mutation was an independent strong predictor of poor OS. KRAS mutation analysis should be included in the routine pathologic evaluation of resected hilar cholangiocarcinoma in order to better stratify prognosis

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Moving the Needle on Precision Medicine in Pancreatic Cancer

Cited by 22 publications

References 86 publications

Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma

Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma

Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

The Impact of KRAS Mutational Status on Long-Term Survival following Liver Resection for Hilar Cholangiocarcinoma

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