
==== Front
JCO Precis Oncol
JCO Precis Oncol
po
PO
JCO Precision Oncology
2473-4284
Wolters Kluwer Health

39102633
PO.24.00167
10.1200/PO.24.00167
00187
ORIGINAL REPORTS
Cancer Genetics
Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma
https://orcid.org/0000-0003-3483-7450
Cremin Carol MSc 1 2 3
https://orcid.org/0000-0002-1652-5560
Bedard Angela C. MS 1
https://orcid.org/0000-0003-2534-3897
Hong Quan MSc 1
Mung Sze Wing BSc 1
Nuk Jennifer MSc 1 3
Wong Andrew BSc 1
Akbar Husain BSc 4
Cheung Eugene MPH 1
Renouf Daniel MD 2 5
Schaeffer David MD 2 6
https://orcid.org/0000-0001-6003-7786
Sun Sophie MD 1 5
https://orcid.org/0000-0002-7413-4314
Schrader Kasmintan A. PhD, MBBS 1 2 3 4
1 Hereditary Cancer Program, BC Cancer, Vancouver, BC, Canada
2 Pancreas Centre BC, Vancouver, BC, Canada
3 Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada
4 Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada
5 Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada
6 Division of Anatomical Pathology, Vancouver General Hospital, Vancouver, BC, Canada
Kasmintan A. Schrader, MD; e-mail: ischrader@bccancer.bc.ca.
2024
05 8 2024
05 8 2024
8 e240016715 3 2024
23 5 2024
25 6 2024
© 2024 by American Society of Clinical Oncology
2024
American Society of Clinical Oncology
https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

PURPOSE

Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic–initiated testing (HCT) pathway and a new oncology clinic–initiated testing (OCT) pathway.

METHODS

Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes.

RESULTS

The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease (P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group (P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306).

CONCLUSION

The real-world observations in our study show that oncology clinic–initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.

Oncology clinic–initiated hereditary cancer testing improves access for patients with pancreatic cancer.

OPEN-ACCESSTRUE
==== Body
pmcINTRODUCTION

Approximately 6,900 Canadians were diagnosed with pancreatic cancer and 5,700 died from this disease in 2022. Ranked as the 11th most commonly diagnosed cancer but the third leading cause of death, pancreatic cancer accounts for 6.7% of all cancer deaths in Canada.1 Because of the late detection and aggressive nature of pancreatic ductal adenocarcinoma (PDAC), the 5-year survival rate is 10% on the basis of Canadian Statistics and about 13% on the basis of SEER data across all stages, making it critical to focus efforts on risk reduction and earlier detection of PDAC.2-4

CONTEXT

Key Objective

Does hereditary cancer testing initiated in oncology clinics increase access and shorten timelines for patients with pancreatic ductal adenocarcinoma (PDAC) compared with testing in hereditary cancer clinics?

Knowledge Generated

The real-world observations in our study show that oncology clinic–initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. Targeting genetic counseling referrals and resources for patients with hereditary findings allows further support and education for patients as well cascade testing in relatives.

Relevance

Oncology clinic–initiated hereditary cancer testing should be offered to all patients with PDAC for its potential to inform first-line treatment decisions and to reduce barriers to hereditary assessment for underrepresented populations.

A hereditary or familial component has been established in approximately 10%-15% of patients with PDAC, a group which can be targeted for early detection and personalized medicine.2,5,6 The range in detection rate is attributed to different testing approaches (eg, size of gene panel and different platforms), referral biases, and populations enriched for founder mutations.2,5,6 Genetic testing for 11 of the well-known inherited pancreatic cancer susceptibility genes has become faster and more affordable through next-generation sequencing (BRCA1, BRCA2, PALB2, ATM, MLH1, MSH2, and MSH6, STK11, CDKN2A, APC, and TP53).7-10 Once an inherited pancreatic cancer susceptibility factor is identified, patients can be offered opportunities for targeted treatments for pathogenic variants (PVs) in select predisposition genes (BRCA1, BRCA2, PALB2, and genes associated with mismatch repair deficiency) at the time of diagnosis or the time of disease progression. Furthermore, at-risk relatives can undergo cascade testing to determine if they have inherited the PV, in which case they can be offered screening for early cancer detection.5,11,12

The National Comprehensive Cancer Network (NCCN) recommends that all patients with PDAC be offered germline multigene panel testing resulting in a significant increased demand for genetic testing and counseling services.12 Genetic testing of patients with PDAC in Canada is primarily offered through referrals to provincial hereditary cancer clinics, which can have long wait times.13,14 Populations referred to hereditary cancer clinics can be subject to referral bias and are often not representative of the target population.15,16

To improve access to hereditary testing for patients with PDAC in British Columbia, we launched oncology clinic–initiated testing in May 2020, thus enabling trained oncologists/nurse practitioners to offer this directly to their patients at point of care. We compared testing outcomes of the hereditary cancer clinic–initiated testing (HCT) pathway and the new oncology clinic–initiated testing (OCT) pathway.

METHODS

The OCT training session was open to all BC Cancer oncologists who treat patients with pancreatic cancer. The 30-minute session was online and included a review of genetic testing and forms/requisitions. Providers including oncologists, general practitioners in oncology, and nurse practitioners from across all five BC regional health authorities completed the training.

Participants were patients with confirmed PDAC referred to a provincial cancer center, BC Cancer, for HCT or OCT between June 1, 2020, and February 1, 2022. All patients were eligible for provincially funded germline testing regardless of age or family history. All patients provided informed consent for testing and received results from a genetic counselor either through telephone call or by letter.

The primary aim was a descriptive analysis of the two populations and measurement of testing outcomes. This retrospective analysis was approved by the BC Cancer Research Ethics Board.

Genetic Testing

All patients were offered genetic testing at no cost using a blood sample. Extracted DNA was sent to a commercial laboratory (Invitae, San Francisco, California; or Ambry Genetics, Aliso Viejo, CA). Genetic testing protocol consisted of next-generation sequencing and deletion-duplication testing of a customized panel of cancer susceptibility genes of varying sizes depending on time (Invitae 84 genes before April 2021, 54 gene panel from April 2021 to December 2021, and an Ambry 76 gene panel from January 2022 onward). Figure 1 illustrates the patient flow during this study period.

FIG 1. OCT and HCT pathways. HCT, hereditary cancer clinic–initiated testing; OCT, oncology clinic–initiated testing; VUS, variant of unknown significance.

Clinical Data

HCT patients were referred by their oncologist or health care provider to the BC Hereditary Cancer Program for a pretest counseling appointment by telephone with a genetic counselor. Family history, medical history, and genetic testing consent were obtained, and the genetic counselor provided a test requisition to the patient via email or mail. Starting October 2021, patients were also given the option to skip the pretest telephone counseling appointment with a genetic counselor and access testing through a web-based testing platform. This online platform featured a brief video that outlined hereditary cancer and genetic testing.

The OCT patient cohort received a package at their oncology appointment that included an information sheet about genetic testing and the following forms to fill out during or after their appointment: consent form, family history form, medical history form, and pretesting survey. These forms replaced the traditional pretest genetic counseling appointment that is offered in the hereditary cancer clinic. The OCT cohort received the requisition for their blood draw directly from their oncology team.

Return of Results

Figure 1 shows the results pathway for OCT and HCT. Patients who had no PVs, concerning variant of unknown significances, or any cancer family history of concern were provided their results by letter. The letter was two pages of plain-language information about their result and the impact for them and family members. Patients who tested positive for a PV had a 1-1 appointment and were also provided with a family information sheet and a phone number for their relatives to call to self-refer for genetic testing. Results appointments were offered to the designated family member if a patient passed away before their result appointment.

Statistical Analysis

Characteristics of patients including age, sex, ethnicity, health authority/cancer center, genetic testing results, and various genetic testing parameters were summarized between the HCT and OCT cohorts. Median (and quartiles) and frequencies (and proportions) were used for continuous variables and categorical variables, respectively. Differences of characteristics of patients between the HCT and OCT cohorts were compared using the parametric (chi-squared test and analysis of variance) or the nonparametric (Fisher's exact test and Wilcoxon test) as appropriate.

A multivariable logistic regression model was conducted to compare testing rate among all referred patients. A subset that only included tested patients was then extracted to determine the wait time from referral date to result disclosure date. Given the right skewed distribution of wait time, a multivariable gamma linear model with a log link function was used to compare the wait time between the two pathways. Both models were adjusted with the characteristic factors that were associated with dependent variables at P < .1 in univariate analyses. A P < .05 was considered significant. All analyses were performed using R version 4.1.0.

RESULTS

Figure 2 shows the overall study population and outcomes including test completion rate and reasons for not completing testing. The demographic and patient characteristics of the overall referred cohorts (n = 397) and the subset that completed testing (n = 306, 77.1%) are shown in Table 1. The HCT cohort was more likely to have European ethnicity, advanced-stage disease, and poorer Eastern Cooperative Oncology Group (ECOG) performance status than the OCT group. ECOG was measured at time of initiating the referral in HCT and at the time of initiating genetic testing in the OCT. Other factors were not significantly different between the HCT and OCT referral cohorts. In the tested subset of patients, similar results were found when we compared the characteristics of OCT and HCT patients, except that OCT patients showed a significantly higher proportion of males compared with HCT patients.

FIG 2. Flowchart of patients with PDAC referred for genetic assessment during the study period. aOne patient completed OCT but passed away before the results being available and the next of kin on file was not reachable. bTwo patients originally referred to the Hereditary Cancer Program and placed on the wait list for pretest counseling were then offered genetic testing directly by their oncology team at a subsequent oncology visit. HCT, hereditary cancer clinic–initiated testing; OCT, oncology clinic–initiated testing; PDAC, pancreatic ductal adenocarcinoma.

TABLE 1. Patient Characteristics

Patient Characteristic	Completed Testing (N = 306)
No. (%) of Patients	All Patients Referred (N = 397)
No. (%) of Patients	
HCT (n = 196)	OCT (n = 110)	P	HCT (n = 279)	OCT (n = 118)	P	
Completed testing	—	—	—	196 (70.3)	110 (93.2)	<.001	
Wait time to results,a days (median, IQR)	107 (64, 158)	53 (44, 76)	<.001	—	—	—	
Wait time to HCT appointment,b days (median, IQR)	35 (19, 90)	—	—	—	—	—	
Age at diagnosis, years, mean (SD)	66.7 (10.7)	68.7 (10.6)	.118	67.0 (10.2)	69.0 (10.5)	.079	
Sex							
 Female	110 (56.1)	47 (42.7)	.033	146 (52.3)	52 (44.1)	.163	
 Male	86 (43.9)	63 (57.3)		133 (47.7)	66 (55.9)		
Ethnicity							
 Africa/Caribbean	3 (1.5)	3 (2.7)	.053	4 (1.4)	3 (2.5)	.021	
 Asian	38 (19.4)	32 (29.1)		42 (15.1)	33 (28.0)		
 European/United Kingdom	140 (71.4)	59 (53.6)		174 (62.4)	61 (51.7)		
 Indigenous	1 (0.5)	0 (0.0)		2 (0.7)	0 (0.0)		
 Other	9 (4.6)	8 (7.3)		12 (4.3)	8 (6.8)		
 Missing	5 (2.6)	8 (7.3)		45 (16.1)	13 (11.0)		
European/United Kingdom							
 Yes	140 (71.4)	59 (53.6)	.010	174 (62.4)	61 (51.7)	.004	
 No	51 (26)	43 (39.1)		60 (21.5)	44 (37.3)		
 Missing	5 (2.6)	8 (7.3)		45 (16.1)	13 (11.0)		
Health authority							
 Greater Vancouver area	107 (54.6)	89 (80.9)	<.001	157 (56.3)	97 (82.2)	<.001	
 Interior	35 (17.9)	6 (5.5)		48 (17.2)	6 (5.1)		
 Northern	5 (2.6)	13 (11.8)		8 (2.9)	13 (11.0)		
 Vancouver Island	49 (25)	2 (1.8)		66 (23.7)	2 (1.7)		
Cancer center							
 Greater Vancouver	114 (58.2)	91 (82.7)	<.001	167 (59.9)	98 (83.1)	<.001	
 Other	82 (41.8)	19 (17.3)		112 (40.1)	20 (16.9)		
Stage at PDAC diagnosis							
 Resectable	25 (12.8)	28 (25.5)	.070	151 (54.1)	56 (47.5)	.012	
 Borderline resectable	15 (7.7)	8 (7.3)		32 (11.5)	30 (25.4)		
 Locally advanced	42 (21.4)	23 (20.9)		23 (8.2)	9 (7.6)		
 Metastatic	105 (53.6)	51 (46.4)		61 (21.9)	23 (19.5)		
 Missing	9 (4.6)	0 (0.0)		12 (4.3)	0 (0.0)		
ECOG at referral							
 0	21 (10.7)	30 (27.3)	.001	27 (9.7)	32 (27.1)	.001	
 1	61 (31.1)	41 (37.3)		72 (25.8)	44 (37.3)		
 2	28 (14.3)	17 (15.5)		46 (16.5)	17 (14.4)		
 3	29 (14.8)	5 (4.5)		39 (14.0)	7 (5.9)		
 4	3 (1.5)	1 (0.9)		4 (1.4)	2 (1.7)		
 Missing	54 (27.6)	16 (14.5)		91 (32.6)	16 (13.6)		
Diabetes							
 No	125 (63.8)	74 (67.3)	.458	176 (63.1)	76 (64.4)	.550	
 Yes	60 (30.6)	28 (25.5)		86 (30.8)	31 (26.3)		
 Missing	11 (5.6)	8 (7.3)		17 (6.1)	11 (9.3)		
Smoking							
 No	91 (46.4)	60 (54.5)	.454	121 (43.4)	63 (53.4)	.240	
 Yes	83 (42.3)	44 (40.0)		124 (44.4)	48 (40.7)		
 Missing	22 (11.2)	6 (5.5)		34 (12.2)	7 (5.9)		
First-degree relatives with PDAC							
 No	181 (92.3)	99 (90.0)	>.999	221 (79.2)	103 (87.3)	.910	
 Yes	15 (7.7)	9 (8.2)		22 (7.9)	9 (7.6)		
 Missing	0 (0)	2 (1.8)		36 (12.9)	6 (5.1)		
Second-degree relatives with PDAC							
 No	185 (94.4)	102 (92.7)	>.999	231 (82.8)	106 (89.8)	>.999	
 Yes	11 (5.6)	6 (5.5)		12 (4.3)	6 (5.1)		
 Missing	0 (0)	2 (1.8)		36 (12.9)	6 (5.1)		
Pathogenic variant	30 (15.3)	19 (17.3)	.774	—	—	—	
Pathogenic variants in pancreatic susceptibility genes	17 (8.7)	9 (8.2)	>.999	—	—	—	
NOTE. Significant P values have been bolded in the table.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; PDAC, pancreatic ductal adenocarcinoma; HCT, hereditary cancer clinic–initiated genetic testing; OCT, oncology clinic–initiated testing.

a Wait time: wait time was calculated from the referral date to the date of release of results.

b Wait time: wait time was calculated from the referral date to pretest counseling date.

Table 2 shows the results of bivariable and multivariable logistic linear models for testing status. There was no significant difference in demographic factors between the HCT and OCT referral cohorts. The multivariable model adjusted for other cancer history, ECOG performance, and smoking status showed that patients in the OCT route were more likely to complete the genetic testing compared with the HCT route (odds ratio, 3.82 [95% CI, 1.69 to 9.84]). Table 3 shows the results of bivariable and multivariable generalized linear modes for wait time. Among 306 tested patients, the median of the wait time in the OCT route from referral date to result disclosure date (53 days, IQR, 44-76) remained significantly shorter compared with the HCT route (107 days, IQR, 64-158) after adjusting sex, age at diagnosis, ECOG status, and smoking history (P = .003). The OCT route resulted in a 51% decrease in time from referral date to result disclosure compared with the HCT route (95% CI, 0.43 to 0.57).

TABLE 2. Bivariable and Multivariable Models for Factors Associated With Test Completion

Variable	Bivariable	Multivariable	
Odds Ratio	95% CI	P	Odds Ratio	95% CI	P	
Pathway							
 HCT	Reference			Reference			
 OCT	5.82	2.88 to 13.5	<.001	3.82	1.69 to 9.84	.003	
Sex							
 Female	Reference						
 Male	0.78	0.49 to 1.24	.296				
Age	1.00	0.97 to 1.02	.721				
Stage							
 Resectable	Reference						
 Borderline resectable	0.43	0.15 to 1.25	.118				
 Locally advanced	0.58	0.23 to 1.36	.222				
 Metastatic	0.52	0.23 to 1.08	.097				
Personal history							
 No	Reference			Reference			
 Yes	1.85	0.96 to 3.86	.081	1.94	0.83 to 5.17	.150	
ECOG							
 0	Reference			Reference			
 1	1.13	0.43 to 2.82	.795	1.20	0.39 to 3.35	.733	
 2	0.39	0.15 to 0.96	.047	0.46	0.15 to 1.30	.157	
 3	0.44	0.16 to 1.19	.110	0.43	0.13 to 1.31	.148	
 4	0.31	0.05 to 2.52	.220	0.29	0.04 to 2.52	.214	
Smoking							
 No	Reference			Reference			
 Yes	0.62	0.37 to 1.03	.066	0.60	0.31 to 1.16	.131	
Family PDAC history							
 No	Reference						
 Yes	0.77	0.35 to 1.87	.532				
Diabetes status							
 No	Reference						
 Yes	0.81	0.49 to 1.37	.431				
European/United Kingdom							
 No	Reference						
 Yes	0.59	0.27 to 1.19	.161				
Cancer center							
 No	Reference						
 Yes	0.95	0.59 to 1.58	.851				
NOTE. Significant P values have been bolded in the table.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; HCT, hereditary cancer clinic–initiated genetic testing; OCT, oncology clinic–initiated testing; PDAC, pancreatic ductal adenocarcinoma.

TABLE 3. Bivariable and Multivariable Models for Factors Associated With Wait Time (in days)

Variable	Bivariable	Multivariable	
Exp (β)a	95% CI	P	Exp (β)	95% CI	P	
Pathway							
 HCT	Reference			Reference			
 OCT	0.50	0.44 to 0.57	<.001	0.49	0.43 to 0.57	<.001	
Sex							
 Female	Reference			Reference			
 Male	0.87	0.74 to 1.02	.078	0.91	0.79 to 1.06	.210	
Age	0.99	0.98 to 1.00	.023	1.00	0.99 to 1.00	.136	
Stage							
 Resectable	Reference						
 Borderline resectable	1.19	0.84 to 1.69	.337				
 Locally advanced	1.09	0.84 to 1.41	.515				
 Metastatic	0.92	0.73 to 1.14	.454				
Personal history							
 No	Reference						
 Yes	1.01	0.83 to 1.23	.946				
ECOG							
 0	Reference			Reference			
 1	1.07	0.84 to 1.35	.568	0.93	0.77 to 1.11	.422	
 2	1.29	0.97 to 1.71	.078	1.07	0.85 to 1.34	.571	
 3	1.01	0.75 to 1.38	.935	0.81	0.63 to 1.05	.122	
 4	0.63	0.33 to 1.39	.204	0.62	0.37 to 1.12	.088	
Smoking							
 No	Reference			Reference			
 Yes	1.19	1.01 to 1.40	.039	1.24	1.07 to 1.43	.004	
Family PDAC history							
 No	Reference						
 Yes	1.01	0.80 to 1.29	.948				
Diabetes status							
 No	Reference						
 Yes	0.93	0.78 to 1.11	.393				
European/United Kingdom							
 No	Reference						
 Yes	1.06	0.89 to 1.26	.507				
Cancer center							
 No	Reference						
 Yes	1.15	0.97 to 1.36	.105				
NOTE. Significant P values have been bolded in the table.

Abbreviations: ECOG, Eastern Cooperative Oncology Group; HCT, hereditary cancer clinic–initiated genetic testing; OCT, oncology clinic–initiated testing; PDAC, pancreatic ductal adenocarcinoma.

a Exponential coefficients.

Among the tested patients, 49 (16%) had a PV detected that required follow-up by the hereditary cancer program (Fig 3). The majority of PVs were identified in pancreatic cancer susceptibility genes (n = 26). Ten patients were identified to harbor PV in other autosomal dominant cancer susceptibility genes and 23 patients harbored PV in genes associated with autosomal recessive conditions with no impact on their cancer risks. There was no significant difference in the proportion of PVs between OCT and HCT. PVs were found most frequently in the ATM and BRCA2 genes. A complete list of all variants is provided in the Data Supplement (Table S1).

FIG 3. (A) Genetic testing results overall (n = 306 patients). (B) Pathogenic variant results (n = 49 patients). PC-PV = patients with pathogenic variants in one of the PC susceptibility genes.a n= 26: ATM, BRCA1, BRCA2, PALB2, MSH2, MSH6, and TP53. Other PV = patients with pathogenic variants in other actionable autosomal dominant cancer susceptibility genes not associated with pancreatic cancer. n = 10: 1 RET, 1 POLE, 2 MITF, 5 CHEK2, and 1 CHEK2/BRIP1. Autosomal recessive (AR) gene PVs = patients with pathogenic variants in genes associated with autosomal recessive conditions. n = 13: 2 CFTR, 1 CFTR/SPINK1, 1 BLM, 1 MSH3, 2 MUTYH, 2 NBN, 3 NTHL1, and 1 REQCL4. aATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PMS2, EPCAM, PALB2, PRSS1, TP53, and STK11. NEG, negative; no variants identified; PC, pancreatic cancer; PV, pathogenic variant; VUS, variant of unknown significance.

To estimate the uptake of cascade testing for the 36 families with autosomal dominant cancer susceptibility PVs, family history was reviewed. We identified 118 relatives potentially eligible for testing in our program. At the time of study data extraction, 18 relatives from 12 families (five OCT and seven HCT) had sought referrals for genetic testing. This represents an uptake of carrier testing of approximately a third of eligible families, with the rate being 15.2% among all potentially eligible individuals and an overall ratio of 0.56 relatives tested per index case.

INTERPRETATION

This study is consistent with the growing body of research that actionable hereditary findings are identified in approximately 10% of unselected patients with pancreatic cancer, supporting the need to reduce barriers to access so that more patients can benefit from precision oncology.17,18 In this study, patients accessing genetic testing through their oncology team as part of their clinic visit (OCT) were almost four times more likely to complete testing compared with patients referred to a provincial hereditary cancer clinic (HCT) and received results in half the time.

The HCT pathway had significant patient drop-offs at the preappointment booking stage (n = 48 patients (17.2%) did not have an appointment booked) and at the sample provision stage (n = 35 patients [12.5%] did not provide a sample after attending the pre-test counseling appointment). There is previous evidence that patients with PDAC are not well served by the traditional genetics referral pathway.19,20 The study by Walker et al showed that only 32% of all patients with PDAC were referred for genetic testing and only 60% of those referred completed genetic testing.

Consistent with other studies, our data show that the lethality of PDAC requires a prompt and streamlined approach to genetic testing in advanced cancers.19-21 We found that 12% of patients referred for hereditary testing did not complete it because of rapid disease progression or death, which was higher in the HCT group and may be related to the more advanced stage in this group. In a study conducted by Yurgelun et al, 11.6% of patients with PDAC died before receiving their genetic testing results, which precluded patients from having the opportunity to therapeutically benefit from results. Results were provided to a designated family member in 18% of cases because of either disease progression and/or death. Although a missed opportunity for the patient to make personal use of their result, this illustrates the practical importance of obtaining next of kin contact information to provide more information for the family and relatives who may be concerned about genetic risk factors for PDAC.10,22

ASCO6 and NCCN recommend genomic testing as part of an initial assessment for all patients with PDAC to ensure that the results of testing are available at the time of treatment decision making.2,12 Patients harboring PVs in BRCA1, BRCA2, or PALB2 can be selected, where appropriate, for platinum-based therapy in the neoadjuvant and adjuvant settings and for maintenance therapy in the metastatic setting with the PARP inhibitor olaparib.12 With more patients being tested and an overall faster return of results, initiating genetic testing at the time of diagnosis increases the potential both for precision medicine in patients and cancer risk reduction in their relatives who can follow well-established gene-specific cancer risk management guidelines.12,18

Although significantly faster than HCT, the median turnaround for results in the OCT group was 53 days, which falls short of allowing results to be incorporated in first-line treatment decisions. The OCT protocol during this study was that oncology providers initiated the testing but all OCT results were embargoed until review and disclosure by a genetic counselor either by a scheduled appointment or by a letter. This additional report review step increased the time to release of results. Since 2022, our program has adopted a true mainstreamed approach with reports going directly back to the ordering oncology team so they can directly disclose results to their patients. This is expected to further reduce the time to results for patients as it is only dependent on laboratory turnaround time. Any positive findings or variants of concern are offered a reflex referral for clinical genetic counseling in the provincial program. Our study found that only a small percentage of patients actively declined genetic testing with a similar rate in both groups (5% in HCT and 3% in OCT). Of those who declined testing (n = 13), chart review suggested similar reasons in both groups: feeling too overwhelmed (n = 4), not interested (n = 4), privacy concerns (n = 3), cancer worry (n = 1), and unknown reason (n = 1).

An important finding in the study was the demonstration that the OCT pathway serves a more ethnically diverse set of patients than that of HCT. To increase the equity and clinical utility of hereditary cancer testing in PDAC, it must be brought outside of traditional genetics clinics. This is critical step in improving access and addressing known cancer health disparities in ethnic minorities.23-27

A future direction for this work is a collaboration with the provincial cancer registry to implement a real-time systematic clinician prompt for mainstreaming testing at the time of pathology confirmation. Another area is to increase cascade testing uptake rate, which was low in our study at only 15.2% of all potentially eligible individuals for an overall ratio of 0.56 relatives tested per index case. In another Canadian study, clinical follow-up in families of 44 patients with pancreatic cancer with PVs showed a 31.2% uptake rate of cascade testing among first-degree relatives and 0.52 new hereditary cases per index case.28 We will explore if a recently implemented practice guideline in our clinic for a supported direct contact approach to sharing information in families increases cascade testing rates. Analysis of rates of non-pancreatic cancer (PC) susceptibility genes in future cohorts tested with broad panel approaches may shed light on new PC associations.

An important strength of this study was the ethnically diverse cohort of patients, particularly within the OCT patient group. Most studies investigating similar programs and approaches to genetic testing have a patient population that is mainly Caucasian and of non-Hispanic ethnicity.5,23,24

The study was limited by a small sample size and further study is needed. Although these preliminary data showed a more diverse referral population in the OCT cohort, no patients identified as having Indigenous ancestry, whereas 5.9% of the BC population overall reported Indigenous identity in the 2021 Canadian Census.29 Self-reported ethnicity data were incomplete or unknown for 16% and 11% of the HCT and OCT cohorts, respectively. Although a majority of the data are complete, there remains a small portion of incomplete data because of the data censoring date (August 1, 2022). Cascade testing uptake estimates were limited as we did not directly survey patients to elicit which relatives they had informed of their result and whether those relatives may have had genetic testing in another jurisdiction. This study was unable to assess reasons a patient might choose not to be referred for testing via OCT or HCT.

In conclusion, OCT reached a more ethnically diverse patient population, and achieved higher testing rates and faster results compared with HCT among patients with PDAC. Many genetics programs, including ours, have moved onward with expanding the mainstream testing approach, which entails direct ordering and disclosure of genetic testing by nongenetics health care providers, with reflex referral to the hereditary cancer program for any concerning results. National resources, including those from the Canadian Association of Genetic Counsellors, have been developed to empower providers and patients in this regard.30 In addition to the benefits shown in this study and others, a mainstreaming approach allows hereditary cancer programs to more effectively focus genetic counseling resources and support for those patients with PVs and facilitating cascade testing for families with hereditary cancer.

ACKNOWLEDGMENT

The authors are grateful for the support of Mandy Jevon, Hereditary Cancer Program Manager, during this study period.

SUPPORT

AUTHOR CONTRIBUTIONS

Conception and design: Carol Cremin, Sze Wing Mung, Jennifer Nuk, Andrew Wong, David Schaeffer, Kasmintan A. Schrader

Financial support: Kasmintan A. Schrader

Administrative support: Husain Akbar, Kasmintan A. Schrader

Provision of study materials or patients: Daniel Renouf, Kasmintan A. Schrader

Collection and assembly of data: Carol Cremin, Angela C. Bedard, Sze Wing Mung, Andrew Wong, Eugene Cheung, Daniel Renouf

Data analysis and interpretation: Carol Cremin, Angela C. Bedard, Quan Hong, Andrew Wong, Husain Akbar, Daniel Renouf, Sophie Sun, Kasmintan A. Schrader

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

K.A.S. acknowledges funding from the Canada Research Chairs program and Canadian Institutes of Health Research. This work was supported in part by the Bob and Judy Hager Family Fund.

Carol Cremin

Employment: BC Cancer, Harrison Healthcare

Travel, Accommodations, Expenses: Precede Consortium

Angela Bedard

Employment: BC Cancer

Jennifer Nuk

Honoraria: AstraZeneca

Andrew Wong

Employment: BC Cancer

Daniel Renouf

Honoraria: Roche, Bayer, Ipsen

Consulting or Advisory Role: Roche, Bayer, Viatris

Research Funding: Bayer, Roche (Inst)

David Schaeffer

Stock and Other Ownership Interests: Satisfai Health, FOCUS Oncology

Honoraria: Diaceutics, Bayer, Amgen, Pfizer

Consulting or Advisory Role: Amgen, Robarts Clinical Trials

Sophie Sun

Honoraria: Pfizer, Bristol Myers Squibb/Pfizer, Novartis Pharmaceuticals Canada, Merck, Takeda

Consulting or Advisory Role: AstraZeneca, Merck, Novartis

Kasmintan A. Schrader

Stock and Other Ownership Interests: Genetics Adviser

Honoraria: AstraZeneca Canada, Precision RxDx, Merck/Pfizer

Consulting or Advisory Role: Pfizer, AstraZeneca, Precision RxDx

Research Funding: AstraZeneca (Inst)

Patents, Royalties, Other Intellectual Property: Parent-of-origin patent application with BC Cancer, part of the Provincial Health Services Authority

Travel, Accommodations, Expenses: AstraZeneca Canada

Other Relationship: Genetics Adviser

No other potential conflicts of interest were reported.
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