Purpose: To evaluate the overall survival of patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC; metastatic tumor <4 cm, ≤2 metastatic tumors total) receiving neoadjuvant therapy, metastasectomy and/or ablation, and primary tumor resection.Methods: We performed a case–control study from January 2005 to December 2015. Patients who underwent curative-intent surgery combined modality therapy (M1 surgery group; 6 [14%], tumor [T]3, node [N]1, and oligo-metastases [M]1) were matched 1 to 3 based on TN stage with two control groups (M0 surgery and M1 no surgery). The M0 surgery group (18 [43%], T3, N1, and M0) included patients without metastases who underwent resection. The M1 no surgery group (18 [43%], T3, N1, and M1) included patients with metastatic PDAC who received palliative chemotherapy without surgical resection.Results: Median overall survival in the M1 surgery, M0 surgery, and M1 no surgery groups was 2.7 years (95% confidence interval [CI], 0.71–3.69), 2.02 years (95% CI, 0.98–3.05), and 0.98 years (95% CI, 0.55–1.25), respectively. Eastern Cooperative Oncology Group (ECOG) status was associated with survival (p = 0.01) after univariate analysis. After adjusting for ECOG status, multivariate analysis showed M1 surgery patients had improved survival compared with M1 no surgery patients and similar survival to M0 surgery patients.Conclusion: Multimodal therapy benefitted our M1 surgery patients. A larger, prospective study of this multidisciplinary management strategy is currently under way.
Cholangiocarcinoma is a heterogeneous and target-rich disease with differences in actionable targets. Intrahepatic and extrahepatic types of cholangiocarcinoma differ significantly in clinical presentation and underlying genetic aberrations. Research has shown that extrahepatic cholangiocarcinoma is more likely to be associated with ERBB2 (HER2) genetic aberrations. Various anti-HER2 clinical trials, case reports and other molecular studies show that HER2 is a real target in cholangiocarcinoma; however, anti-HER2 agents are still not approved for routine administration. Here, we show in a metastatic cholangiocarcinoma with ERBB2 amplification identified on liquid biopsy (circulating tumor DNA (ctDNA) testing), a dramatic response to now over 12 months of dual-anti-HER2 therapy. We also summarize the current literature on anti-HER2 therapy for cholangiocarcinoma. This would likely become another treatment option for this target-rich disease.
Purpose. Recent advances in molecular diagnostic technologies allow for the evaluation of solid tumor malignancies through noninvasive blood sampling, including circulating tumor DNA profiling (ctDNA). Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, often because of late presentation of disease. Diagnosis is often made using endoscopic ultrasound or endoscopic retrograde cholangiopancreatography, which often does not yield enough tissue for next-generation sequencing. With this study, we sought to characterize the ctDNA genomic alteration landscape in patients with advanced PDAC with a focus on actionable findings. Materials and Methods. From December 2014 through October 2019, 357 samples collected from 282 patients with PDAC at Mayo Clinic underwent ctDNA testing using a clinically available assay. The majority of samples were tested using the 73gene panel which includes somatic genomic targets, including complete or critical exon coverage in 30 and 40 genes, respectively, and in some, amplifications, fusions, and indels. Clinical data and outcome variables were available for 165 patients; with 104 patients at initial presentation. Results. All patients included in this study had locally advanced or metastatic PDAC. Samples having at least one alteration, when variants of unknown significance (VUS) were excluded, numbered 266 (75%). After excluding VUS, therapeutically relevant alterations were observed in 170 (48%) of the total 357 cohort, including KRAS (G12C), EGFR, ATM, MYC, BRCA, PIK3CA, and BRAF mutations. KRAS, SMAD, CCND2, or TP53 alterations were seen in higher frequency in patients with advanced disease. Conclusion.Our study is the largest cohort to date that demonstrates the feasibility of ctDNA testing in PDAC. We provide a benchmark landscape upon which the field can continue to grow. Future applications may include use of ctDNA to guide treatment and serial monitoring of ctDNA during disease course to identify novel therapeutic targets for improved prognosis. The Oncologist 2021;25:1-10 Implications for Practice: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis often due to late presentation of disease. Biopsy tissue sampling is invasive and samples are often inadequate, requiring repeated invasive procedures and delays in treatment. Noninvasive methods to identify PDAC early in its course may improve prognosis in PDAC. Using ctDNA, targetable genes can be identified and used for treatment.
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