Introduction

Approximately 10% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) carry a pathogenic variant in a PDAC susceptibility gene. Current guidelines recommend offering germline cancer susceptibility testing for all individuals with PDAC regardless of family history. Previous studies have shown moderate rates of uptake of gene testing, highlighting the need for efficient and accessible clinical pathways for delivering gene testing education and counseling. We evaluated the uptake of gene testing when offered at the point-of-care by an oncology nurse specialist in an outpatient setting.

Aims & Methods

We undertook a retrospective chart review of PDAC patients treated at the Johns Hopkins Hospital between January 2021 and December 2023. Patients were educated about germline testing by an oncology nurse specialist during their initial clinic visit, and provided with instructional handouts, links to videos, instructions on kit ordering and given time to consider testing. “MyChart” reminders are sent as needed. Patients who desired testing were sent a saliva kit to their home that they had to send back to the testing lab. Results were communicated by the oncology nurse to the patients, and those with pathogenic variants or variants of uncertain significance (VUS) are referred to formal genetic counseling.

Results

Of 1022 patients seen by the oncology and surgery teams, all but 2 were seen by oncology, 377 underwent surgery, 52% were male, 74.9% were White, 15.8% African American (AA), 6% were Asian, 3% were Hispanic, and 17.5% had a family history of pancreatic cancer. At diagnosis, median age was 67.1 +/- 10.6 years; 51.9% of cases had resectable-stage disease.
Among the 87.5% of patients offered gene testing, 77.6% completed testing. Completion rates among those offered testing increased from 72.4% (2021) to 78.5% (2022) and 82.2% (2023).
Factors significantly associated with reduced gene testing uptake included African American patients, those that were single, had advanced-stage disease, did not receive chemotherapy and of older age at diagnosis (Table 1).
Among tested individuals, 55 (7.9%) involving PDAC susceptibility genes, with BRCA2, ATM and PALB2 being the most common. 50 out of these 55 patients (91%) were referred to genetic counseling, with 76% completing their counseling visit to date. Germline testing results led to a change in the treatment regimen in 23 of the 55 patients.

Conclusion

The implementation of point-of-care encounters for cancer susceptibility gene testing by an oncology nurse specialist in the outpatient setting yielded a high uptake of testing. African American, older-age, single and advanced-stage disease individuals had lower rates of completing gene testing.

Introduction

Early detection and removal of colorectal adenomatous lesions is effective in reducing the incidence and mortality of colorectal cancer. To achieve this, it is important to improve the detection of colorectal lesions. Newly endoscopy technology, texture and color enhancement imaging (TXI) is expected to enhance visibility of lesion by adjusting the color, structure, and brightness of images taken with white-light imaging (WLI) using EVIS X1 system (Olympus Medical Systems Co., Tokyo, Japan). Our previous retrospective study indicated that TXI improve the detection of colorectal neoplastic lesions. However, it is unclear that ability of detection in TXI is superior to that of WLI.

Aims & Methods

We conducted a prospective multicenter randomized controlled trial to verify the efficacy of TXI in the detection of colorectal neoplastic lesions, when compared with WLI (jRCT1032230089).This trial was conducted at 8 institutions in Japan between May and November 2023. The eligibility criteria included patients aged 20–80 years who were scheduled for screening, post-endoscopic surveillance, or work-up for a positive fecal immunochemical test or abdominal symptoms. Patients were randomly assigned (1:1) to TXI or WLI (control group). In all colonoscopies, EVIS X1 system and CF-EZ1500DI were used. The primary endpoint was mean adenoma per procedure (MAP) in per protocol set (PPS). Other endpoints included adenoma detection rate (ADR), advanced ADR (advanced adenoma: more than 10 mm in diameter, villous or tubulovillous in histology, or high-grade dysplasia), polyp detection rate (PDR), and flat polyp detection rate (FDR). We assumed the TXI mode observations to have an improvement effect of MAP with a difference of δ=0.3 on WLI and the standard deviations of MAP in TXI and WLI were expected to be 1.8 and 1.3, respectively. The required number of subjects for analysis was calculated to be 960, considering an expected dropout rate of 10%, when the two-sided significance level was set at 0.05 and power at 0.8.

Results

A total of 960 patients were enrolled. In PPS, 896 patients were analyzed (451 in TXI and 445 in WLI). In MAP, there was no statistically significant difference between the groups (TXI: 1.4 [95% CI: 1.2-1.6] vs. WLI: 1.5 [1.3-1.7]). ADR was similar in the groups (57.21% [52.49-61.82] vs. 55.96 [51.20-60.63]). Advanced ADR tend to be higher in TXI than WLI (11.09% [8.34-14.35] vs. 8.54[6.11-11.53]). PDR was significantly higher in TXI than WLI (82.48% [78.65-85.88] vs. 74.38 [70.06-78.38]. FDR was significantly higher in TXI than WLI (76.50% [72.31-80.34] vs. 70.34 [65.86-74.55]).

Conclusion

This trial could not show the superiority of TXI over WLI in MAP and ADR. However, it showed that of TXI over WLI in PDR and FDR, indicating that TXI may have ability to detect more flat colorectal lesions which have malignant potential or are difficult to detect.

Introduction

In pancreatic ductal adenocarcinoma (PDAC), the prognostic relevance of B cells remains controversial, and only when aggregated within tertiary lymphoid structures (TLS) have they been unanimously associated with extended survival. Our aim is to provide the first transcriptomic characterization of B cell subtypes and gain new insights into the immune-promoting role of TLS in PDAC.

Aims & Methods

We generated a comprehensive transcriptomic atlas of tumor-associated B cells in PDAC by integrating single cell technology with spatial transcriptomic approaches. Histological characterization of the B cell immune landscape was performed using a novel multiplexed immunohistochemistry panel in treatment-naïve PDAC patients. In addition, TLS assessment on routine H&E slides from two independent PDAC cohorts, comprising participants from the randomized controlled PREOPANC trial (n=44) and the PanGenEU study (n=66), were subjected to uni- and multivariate prognostic analyses, with associated bulk-RNAseq data utilized for additional validation.

Results

The presence of TLS was linked with an expansion of the B cell compartment and their differentiation into antibody-producing plasma cells. Using single nucleus (sn)RNAseq and spatial mapping, we uncovered that certain differentiated B cell subtypes including germinal center (GC) B cells and plasma cells, were exclusively identified in patients with late-stage TLS harbouring GCs. In addition, CD38+ CD138+ plasma cells were predominantly located forming clusters in stromal regions situated in close proximity to TLS. Accordingly, the expression of antibody production and plasma cell markers was significantly heightened in patients with late-stage TLS, indicative of augmented adaptive immune responses. We further validated the prognostic significance of GC formation within TLS in two independent PDAC cohorts (HR=0.45, 95%CI 0.27-0.77, P.adj.=0.034). Notably, in the PREOPANC cohort a positive TLS status was also associated with a favorable immune milieu enriched with antibody-presenting cells and B cell subsets, including plasma cells.

Conclusion

Our multiomic analysis unveils compelling evidence of selective B cell maturation and active adaptive immunity in PDAC patients harboring late-stage TLS. From a clinical perspective, TLSs emerge as robust prognosticators of survival in PDAC. Overall, our findings provide novel insights into B cell biology and hold potential to refine immunotherapeutic strategies in this challenging tumor context.

Disclosure

Nothing to disclose

Introduction

Acetic acid chromoendoscopy (AAC) is frequently used in Barrett esophagus (BE) surveillance endoscopies. AAC is believed to be useful as a ‘red flag’ technique, thereby improving the overall neoplasia detection and the diagnostic yield of targeted biopsies. Accurate targeted neoplasia detection with AAC therefore holds the promise of abandoning random four-quadrant biopsies at 2cm intervals of the BE segment. Although some data exist on the use of AAC in expert centers, the added value in a non-dysplastic surveillance population in routine clinical practice is currently unclear.

Aims & Methods

A prospective stepped wedge cluster randomized trial was conducted in 18 Dutch community hospitals. BE patients undergoing surveillance endoscopies were eligible, while those with known or previously treated dysplasia were excluded. Participating hospitals shifted from usual care (no AAC; control group) to the incorporation of AAC (AAC; intervention group) in randomized order. Endoscopists were trained in the use and assessment of AAC immediately prior to its implementation. In both study groups, targeted biopsies were obtained in the presence of visible lesions before the acquisition of random four-quadrant biopsies. Primary endpoint was the overall neoplasia detection rate, defined as the percentage of patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in both targeted and random biopsies, confirmed by an experienced GI pathologist. Secondary endpoint was the neoplasia detection rate of targeted biopsies. Data were analyzed using an as-treated approach, employing mixed effects regression analyses with a random intercept per hospital and correction for calendar time and BE length.

Results

We included 2,267 patients (1570 males; mean age 66) between June 2020 and November 2023. A total of 1,438/2,267 (63%) patients were allocated to usual care and 829/2,267 (37%) to AAC. In patients allocated to AAC, AAC was applied in 679/829 patients (82%). Overall, 163/2,267 patients (7.2%) were diagnosed with neoplasia, which encompassed LGD in 111/2,267 patients (4.9%), HGD in 30/2,267 patients (1.3%), and EAC in 22/2,267 patients (1.0%). The use of AAC did not result in a significantly higher overall neoplasia detection rate (7.4% with AAC [50/679 patients] versus 7.1% without AAC [113/1,588 patients]; OR 0.97; 95% CI 0.65-1.44). Visible lesions were detected in 95/679 (14.0%) patients receiving AAC versus 101/1,588 (6.4%) patients receiving usual care (p<0.001), yet the targeted neoplasia detection rate was not significantly higher (2.1% [14/679 patients] versus 1.8% [29/1,588 patients]; OR 1.05; 95% CI 0.49-2.24). Neoplasia was detected by random four-quadrant biopsies in the majority of patients: 39/50 patients (78%) receiving AAC and 81/113 patients (72%) receiving usual care.

Conclusion

The use of AAC does not improve the overall or targeted neoplasia detection rate in BE patients undergoing endoscopic surveillance in routine clinical practice. Endoscopic surveillance with AAC-guided targeted biopsies cannot replace the random biopsy protocol.

Disclosure

Pentax Medical, C2 Therapeutics