Pancreatic Cancer Surveillance in Carriers of a Germline <i>CDKN2A</i> Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up

Klatte, Derk C.F.; Boekestijn, Bas; Wasser, Martin; Shahbazi, Shirin Feshtali; Ibrahim, Isaura S.; Mieog, J. Sven D.; Luelmo, Saskia; Morreau, Hans; Potjer, Thomas P.; Inderson, Akin; Boonstra, Jurjen J.; Dekker, Friedo W.; Vasen, Hans F. A.; Hooft, Jeanin E. van; Bonsing, Bert A.; Leerdam, Monique E. van

doi:10.1200/jco.22.00194

Cited by 57 publications

(87 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With these studies 7,27 demonstrating encouraging long-term outcomes from an aggregate of . 7,200 patient-years of surveillance data, this is an opportune time to take stock of what we have learned from these 2 decades and, just as importantly, where the field needs to go from here.…”

mentioning

confidence: 98%

“…In the articles that accompany this editorial, Klatte et al 7 and Dbouk et al 27 presented more than 20 years' worth of prospective data investigating imaging-based pancreatic cancer surveillance in individuals with genetic/familial high risk, demonstrating high rates of resectability and encouraging long-term survival in those with screen-detected pancreatic cancer. These findings reinforce clinical practice guidelines which recommend magnetic resonance imaging-/endoscopic ultrasound-based pancreatic cancer surveillance for genetically high-risk individuals with a family history of pancreatic cancer and also highlight gaps in knowledge about whether and how to expand such surveillance to all individuals with germline susceptibility.…”

mentioning

confidence: 99%

“…With these studies 7,27 demonstrating encouraging long-term outcomes from an aggregate of > 7,200 patient-years of surveillance data, this is an opportune time to take stock of what we have learned from these 2 decades and, just as importantly, where the field needs to go from here. Both studies 7,27 demonstrate that PDAC early detection is indeed possible with frequent imaging-based surveillance, with 80%-90% resectability among screen-detected cases. More importantly, these data show a significant signal that early PDAC detection may confer improved survival.…”

mentioning

confidence: 99%

“…Another major uncertainty is whether these encouraging findings 7,27 can be replicated outside of the high-volume academic centers in which these studies were performed. Indeed, guidelines from ASCO, 19 the National Comprehensive Cancer Network, 23 and the International CAPS consortium 24 all recommend that MRI-/EUS-based PDAC surveillance be performed in centers with experience and expertise in performing and interpreting surveillance.…”

mentioning

confidence: 99%

“…Additionally, some payers are now markedly restricting patients' access to preventative care in high-volume centers, for example by specifically classifying computed tomographies and MRIs as not medically necessary when ordered in hospital-based settings for cancer screening in high-risk individuals. 34 Understanding how to scale and implement PDAC surveillance outside of academic medical centers while preserving these encouraging outcomes 7,27 will be essential to making a meaningful dent in PDAC mortality. The issue of scale could potentially be addressed by the development/validation of blood-based biomarkers for PDAC surveillance.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Yurgelun

2022

JCO

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Yurgelun

2022

JCO

View full text Add to dashboard Cite

show abstract

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

Blackford,

Canto,

Dbouk

et al. 2024

JAMA Oncol

View full text Add to dashboard Cite

ImportancePancreatic ductal adenocarcinoma (PDAC) is a deadly disease with increasing incidence. The majority of PDACs are incurable at presentation, but population-based screening is not recommended. Surveillance of high-risk individuals for PDAC may lead to early detection, but the survival benefit is unproven.ObjectiveTo compare the survival of patients with surveillance-detected PDAC with US national data.Design, Setting, and ParticipantsThis comparative cohort study was conducted in multiple US academic medical centers participating in the Cancer of the Pancreas Screening program, which screens high-risk individuals with a familial or genetic predisposition for PDAC. The comparison cohort comprised patients with PDAC matched for age, sex, and year of diagnosis from the Surveillance, Epidemiology, and End Results (SEER) program. The Cancer of the Pancreas Screening program originated in 1998, and data collection was done through 2021. The data analysis was performed from April 29, 2022, through April 10, 2023.ExposuresEndoscopic ultrasonography or magnetic resonance imaging performed annually and standard-of-care surgical and/or oncologic treatment.Main Outcomes and MeasuresStage of PDAC at diagnosis, overall survival (OS), and PDAC mortality were compared using descriptive statistics and conditional logistic regression, Cox proportional hazards regression, and competing risk regression models. Sensitivity analyses and adjustment for lead-time bias were also conducted.ResultsA total of 26 high-risk individuals (mean [SD] age at diagnosis, 65.8 [9.5] years; 15 female [57.7%]) with PDAC were compared with 1504 SEER control patients with PDAC (mean [SD] age at diagnosis, 66.8 [7.9] years; 771 female [51.3%]). The median primary tumor diameter of the 26 high-risk individuals was smaller than in the control patients (2.5 [range, 0.6-5.0] vs 3.6 [range, 0.2-8.0] cm, respectively; P &lt; .001). The high-risk individuals were more likely to be diagnosed with a lower stage (stage I, 10 [38.5%]; stage II, 8 [30.8%]) than matched control patients (stage I, 155 [10.3%]; stage II, 377 [25.1%]; P &lt; .001). The PDAC mortality rate at 5 years was lower for high-risk individuals than control patients (43% vs 86%; hazard ratio, 3.58; 95% CI, 2.01-6.39; P &lt; .001), and high-risk individuals lived longer than matched control patients (median OS, 61.7 [range, 1.9-147.3] vs 8.0 [range, 1.0-131.0] months; 5-year OS rate, 50% [95% CI, 32%-80%] vs 9% [95% CI, 7%-11%]).Conclusions and RelevanceThese findings suggest that surveillance of high-risk individuals may lead to detection of smaller, lower-stage PDACs and improved survival.

show abstract

Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications

Zhao

Li²,

Wang

et al. 2023

Cancer Medicine

View full text Add to dashboard Cite

Background Approximately 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by the untargetable non‐G12C KRAS mutations, and only a small subset of patients are eligible for FDA‐approved precision therapies. The practice of precision therapy in pancreatic cancer was limited by the paucity of targetable genetic alterations, especially in the Asian population. Methods To explore therapeutic targets in 499 Chinese PDAC patients, a deep sequencing panel (OncoPanscan™, Genetron health) was used to characterize somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants. Results We performed genomic profiling in 499 Chinese PDAC patients, which revealed somatic driver mutations in KRAS, TP53, CDKN2A, SMAD4, ARID1A, RNF43, and pathogenic germline variants (PGVs) in cancer predisposition genes including BRCA2, PALB2, and ATM. Overall, 20.4% of patients had targetable genomic alterations. About 8.4% of patients carried inactivating germline and somatic variants in BRCA1/2 and PALB2, which were susceptible to platinum and PARP inhibitors therapy. Patients with KRAS wild‐type disease and early‐onset pancreatic cancer (EOPC) harbored actionable mutations including BRAF, EGFR, ERBB2, and MAP2K1/2. Compared to PGV‐negative patients, PGV‐positive patients were younger and more likely to have a family history of cancer. Furthermore, PGVs in PALB2, BRCA2, and ATM were associated with high PDAC risk in the Chinese population. Conclusions Our results demonstrated that a genetic screen of actionable genomic variants could facilitate precision therapy and cancer risk reduction in pancreatic cancer patients of Asian ethnicity.

show abstract

Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up

Cited by 57 publications

References 34 publications

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Building on More Than 20 Years of Progress in Pancreatic Cancer Surveillance for High-Risk Individuals

Pancreatic Cancer Surveillance and Survival of High-Risk Individuals

Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications

Contact Info

Product

Resources

About