Evolution of pancreatic ductal adenocarcinoma diagnosis during the last decade

Background: Pancreatic Ductal Adenocarcinoma (PDAC) has historically been an important diagnostic and therapeutic challenge. The multidisciplinary approach and new diagnostic techniques' implementation have modified this process. Method(s): We conducted a retrospective analysis based on clinical data of patients with PDAC between the years 2010 to 2021, analyzing the diagnosis and initial treatment evolution. Result(s): 673 patients between 2010-2021 with a suspected diagnosis of pancreatic adenocarcinoma were reviewed. Most of them were metastatic (n=362;53.8%), followed by locally advanced unresectable (n=166;24.7%) and resectable or borderline resectable (n=145;21.5%). Regarding the pathological diagnosis, it was not possible in 62 patients (9.2%), varying over time from 21.2%in 2010-2012 to 1% in 2019-2021 (p<0,0001). Moreover, the number of biopsies has decreased with a mean number of biopsies to obtain a pathological diagnosis of 1.55 (2010-2012) vs 1.31 (2019-2021). During this last period, most of the diagnoses were made by cytological analysis (61.4%;n=121). Specifically in the 2019-2021 patients subgroup, we found that 18 NGS (9,1%) were performed in this period (solid tumor), with 4 patients having actionable mutations (22.2%;3 KRAS G12C). Germline (g) mutational panels were carried out in 89 patients, finding only 9 positive cases (10.1%), being 3 of them gBRCA1/2 mutated (3,4%). In our study, a decrease in palliative management was evidenced over time. In 2010-2012, 28,8% of patients received exclusively palliative care against 9,6% in 2019-21 (p, 0.0001). An increase in PDAC diagnosis was observed since 2010, 44 patients/year in 2010-12 vs. 66 patients/year in 2019-21 (including COVID-19 pandemic period). All previous results are summarized. Conclusion(s): The diagnosis of PDAC has changed throughout the last decade, increasing the percentage of patients with a pathological diagnosis without increasing the number of invasive procedures. The number of patients suitable for anti-cancer therapy has also increased among time. In our cohort, the implementation of molecular testing would change the therapeutic approach in more than 20% of patients.

Gastrointestinal Cancer and Vaccination Safety during COVID-19 Pandemic

BACKGROUND: During our past 18 months, we must be faced with the current COVID-19 pandemic era with much uncertainty in the continuation of multimodality treatment of the gastrointestinal cancer patients. Especially in this immunocompromised group with the history of previous chemotherapy treatment, these patients have an increased risk of COVID-19 transmission. Many studies have been reported about the current recommendation for gastrointestinal cancer patients during this pandemic, but there might be a lack of evidence about the safety of vaccination for the gastrointestinal cancer patients. AIM: Since the vaccination has been approved by our government medical support, we would evaluate the safety of the COVID-19 vaccination program in gastrointestinal cancer patients. METHODS: All gastrointestinal cancer patients who have been already diagnosed with cancer will be included in this study. The vaccine-related sign symptoms will be recorded and evaluated. The chemotherapy schedule was not been interrupted following the vaccination. The patient who refused to receive the second vaccination dose will be excluded from this study. RESULTS: Thirty-two patients were included in this study (our past 6-month evaluation from February till August 2021), colorectal adenocarcinoma was the most common gastrointestinal cancer according to organ-specific (25 patients), the others were gastric adenocarcinoma, pancreatic adenocarcinoma, and small bowel gastrointestinal stromal tumor. Both of them already received two doses of COVID-19 vaccine during this period, we reported there was no side effect related to these and the chemotherapy cycle has not been interrupted during vaccination. All of the patients could be tolerated it well and did not refuse to continue the treatment. CONCLUSION: There were no significant signs and symptoms of vaccine-related side effects on gastrointestinal cancer patients. COVID-19 vaccination during this pandemic and following the chemotherapy schedule on any kind of gastrointestinal cancer patients was safe and could be suggested as a routine protocol.

DREAMM-9: PHASE I STUDY OF BELANTAMAB MAFODOTIN PLUS STANDARD OF CARE IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Background: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is a standard of care for newly diagnosed multiple myeloma (NDMM). Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma tumor immune response. Belamaf has demonstrated deep and durable responses as a monotherapy in the DREAMM-2 study of patients (pts) with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. Aims: To evaluate the safety and tolerability of this combination in adult pts with transplant-ineligible (TI) NDMM and establish the recommended Phase III dose. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized study of belamaf + VRd. The belamaf dose cohorts currently being evaluated are Cohort 1 (1.9 mg/kg Q3/4W), Cohort 2 (1.4 mg/kg Q6/8W), Cohort 3 (1.9 mg/kg Q6/8W), Cohort 4 (1.0 mg/kg Q3/4W), and Cohort 5 (1.4 mg/kg Q3/4W). Belamaf is given with VRd Q3W until Cycle 8, and with Rd Q4W thereafter. After evaluation of safety data for Cohort 1, Cohorts 2-5 were opened in parallel and enrolled pts were randomized 1:1:1:1. Primary endpoint is safety. Secondary endpoints include efficacy, tolerability, and pharmacokinetics (PK). Results: As of data cutoff (07 Dec 2021), 64 pts were analyzed across all cohorts. Median age (range) was 73.0 (51- 88) years, 55% were male, 80% were white, 8% had extramedullary disease, 59% were International Staging System stage II or III, 20% had amp1q, and 17% had high-risk cytogenetics (≥1 of: t(4;14), t(14;16), del17p). The median duration of follow-up varied: Cohort 1 (17.4 months [mo]), Cohort 2 (5.9 mo), Cohort 3 (6.1 mo), Cohort 4 (4.7 mo), Cohort 5 (5.8 mo). Median number of belamaf cycles were: Cohort 1 (6), Cohort 2 (3), Cohort 3 (3.5), Cohort 4 (4.5), and Cohort 5 (5). Most common adverse events (AEs) across cohorts included thrombocytopenia (49%), constipation (43%), diarrhea (32%), and peripheral sensory neuropathy (30%). AEs related to study treatment were experienced by 61 (97%) pts. Belamaf-related grade 3/4 AEs occurred in 24 (38%) pts. Belamaf dose reductions occurred in 11 (18%) pts, with dose delays in 10 (16%) pts. Three pts experienced a fatal severe AE (unrelated to study treatment);2 due to COVID-19 infection, 1 due to pancreatic adenocarcinoma. Early deep responses were observed;67-92% pts achieved ≥very good partial response (VGPR) (Table), with median time to VGPR of 2.1-2.9 months across cohorts. Of pts with ≥VGPR, 17 were minimal residual disease (MRD) negative, 10 in Cohort 1. As of data cutoff, 8-75% of pts achieved best response of complete response (CR) or stringent CR (sCR). Grade 3 corneal exam findings were reported in 25-58% of pts;grade 3 visual acuity changes were reported in 21-75% of pts. No grade 4 corneal exam findings or visual acuity changes were reported in pts receiving belamaf Q6/8W, compared with 0-17% and 0-8%, respectively, in the Q3/4W cohorts. Belamaf PK profile was similar to that in pts with RRMM, accounting for baseline characteristics. Image: Summary/Conclusion: Belamaf + VRd demonstrated high response rates in pts with TI NDMM, with a high rate of MRD negativity indicating deep responses. No new safety signals were observed relative to DREAMM-2. Study is ongoing to evaluate the safety and efficacy of variable dose intensities of belamaf in combination with VRd.

Delay in Treatment Initiation Increases Mortality in Non-Metastatic Extrahepatic Bile Duct Cancer

INTRODUCTION: Time from diagnosis to treatment initiation for many cancers is lengthening. During the COVID pandemic, many institutions were forced to postpone cancer treatment to reallocate resources, despite the unclear impact of treatment delays. This study sought to investigate the association between time to treatment initiation (TTI) and overall survival in patients with hepatopancreatobiliary (HPB) cancers. METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with de novo cancers of the pancreas, liver, and intrahepatic and extrahepatic bile ducts between 2004 and 2017. Kaplan-Meier survival analysis and Cox regression were used to investigate the association between TTI and overall survival for each cancer type, stratified by stage. Multivariable linear regression identified factors associated with longer TTI. RESULTS: Of 318,931 patients with HPB cancer, median TTI across all cancers was 31 days, ranging from 26 days for pancreas cancer to 48 days for liver cancer. Longer TTI was associated with increased mortality in patients with stages I, II, and III extrahepatic bile duct (EHBD) cancer (Figure 1), and stage I pancreatic adenocarcinoma. Compared to TTI of 3 to 30 days, the risk-adjusted hazard ratios for stage I EHBD cancer for TTI 31 to 60, 61 to 90, and ≥90 days were 1.17 [95% CI 1.07-1.29], 1.39 [1.21-1.59], and 1.63 [1.40-1.90], respectively. For the same time frames, hazard ratios in stage I pancreatic cancer were 1.08 [1.03-1.13], 1.19 [1.11-1.28], and 0.99 [0.90-1.09], respectively. Factors most strongly associated with increased TTI for all cancers included treatment with radiation only (β = +14.1 days, p< 0.001), early stage disease (+13.8 days for stage I vs. stage IV, p< 0.001), Black race (+4.4 days, p< 0.001), Hispanic ethnicity (+4.2 days, p< 0.001), and treatment in the West (+3.9 days vs. Northeast, p< 0.001). CONCLUSIONS: Delayed initiation of definitive therapy leads to increased mortality in stage I-III EHBD and stage I pancreatic cancer. Some patients, including Blacks and Hispanics, are more likely to experience delayed care. Treatment initiation for these cancers should be expedited, and pandemic-related postponements should be avoided if possible.

HYBRID ENDOSCOPIC ULTRASOUND IN THE COVID-19 ERA FOR THE TISSUE DIAGNOSIS OF SOLID LESIONS: AN INITIAL EXPERIENCE FROM A TERTIARY CARE CENTRE IN PAKISTAN

AIM: Endoscopic Ultrasound (EUS) is well-established mode of intervention for tissue acquisition in solid organs with rapid on-site evaluation (ROSE). In the Covid-19 era implementation of infection control mechanisms has led modified hybrid technique to get high diagnostic yield for tissue sampling. Combination of Covid-19 SOPs and tissue acquisition method outline this hybrid technique to get high diagnostic Yield.We share our initial experience of EUS cases performed with this approach without ROSE. METHODS: All 84 cases who underwent EUS guided biopsy from June 2020 till December 2021 were included. The Procedure was done in a negative pressure room with all SOPs as per institutional guidelines for patient and staff safety with a minimum number of persons during procedure. RESULTS: Among these cases, 55 were male, mean age 56 years (range 22-90), Mean duration of procedure 25 min mean (10-90 min). 63 came for organ targeted for malignant pathology include pancreas 35, liver 02, lymph nodes 17, subepithelial lesions 06, mediastinal lesions 08, common-bile duct/gall bladder 04. 17 cases had a multi-targeted biopsy for the additional staging of disease. The number of 'passes' with the needle was average 02 with single pass 17, two pass 39, three passes 11, multitarget single pass in 17. Needle size (Franseen design) used for procedures was 22G in 78 cases and 25G in 6. Common tissue diagnoses include pancreatic adenocarcinoma 26, neuroendocrine tumours 04, tuberculosis 05, gastrointestinal stromal tumours 02, leiomyoma 03, lymphoma 03, metastatic renal cell carcinoma 04, squamous cell carcinoma 04, cholangiocarcinoma/ gall bladder adenocarcinoma 07, Sarcoma 02 and solid pseudopapillary epithelial neoplasm of pancreas (SPEN) 01. There were no immediate or early complications in all cases. CONCLUSIONS: Hybrid EUS in Covid 19 Era has emerged as a useful/cost-effective and safe approach to get tissue yield without the need for ROSE.

MULTI-TARGET ENDOSCOPIC ULTRASOUND EUS-M GUIDED BIOPSY IS SUPERIOR TO PET SCAN FOR STAGING MALIGNANCIES

AIM: EUS modality to get tissue diagnosis and with multi-target approach can help stage disease more accurately with histopathological results. METHODS: Total of 15 cases underwent EUS-M from June 2020 till Dec 2021. Informed consent was obtained, with Covid screen test with PCR was performed before procedure. Procedures were done with all SOPs as per institutional guidelines. 22G FNB needle with Franseen design with capillary suction method used to obtain visible core samples for histopathology without ROSE. All cases have confirmed histopathological diagnosis with same pathology from other site of Biopsy. Order of Biopsy was Nodes→Liver metatatic lesion→Primary Tumor. In cases of nodes mediastinal→portahepatis/ pancreatic→Para-aortic RESULTS: Among total 15 cases, Age 55 Mean (22-74) with 08 Males. Duration of procedure 41 min Mean (20-85). Cases with multiple lymphadenopathy from different anatomical regions were 05 while other sites include Liver for metastasis and Primary tumor from pancreas/CBD in 10 cases. Multiple site single pass was performed in 14 cases. Final diagnosis of Disease was pancreatic adenocarcinoma 05, NETs 01, Lymphoma 03, GB Adenocarcinoma/Cholangiocarcinoma 05 and metastatic RCC 01. All procedures were done under Conscious sedation as day care procedure. There were no immediate or early complication in all cases. CONCLUSIONS: EUS-M is safe and accurate modality to stage malignancy with superiority over PET Scan to obtain histological diagnosis.