Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas

Wo, Jennifer Y.; Clark, Jeffrey W.; Eyler, Christine E.; Mino‐Kenudson, Mari; Klempner, Samuel J.; Allen, Jill N.; Keane, Florence K.; Parikh, Aparna R.; Roeland, Eric; Drapek, Lorraine C.; Ryan, David P.; Corcoran, Ryan B.; Seventer, Emily Van; Fetter, Isobel J.; Shahzade, Heather A.; Khandekar, Melin J.; Lanuti, Michael; Morse, Christopher R.; Heist, Rebecca S.; Ulysse, Christine A.; Christopher, Benjamin; Baglini, Christian V.; Yeap, Beow Y.; Mullen, John; Hong, Theodore S.

doi:10.1158/1078-0432.ccr-21-0331

Cited by 13 publications

(8 citation statements)

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“…Although some studies have shown ctDNA-positivity to be associated with inferior patient outcomes, most of these studies have used a static gene panel-based NGS approach or droplet digital PCR, which may have lower sensitivity. 21,23,24,[26][27][28] Unlike predesigned ctDNA static panels, Signatera is a personalized, tumor-informed assay that relies on the prior knowledge of the mutational status of the patient's tumor. This tumor-informed approach ensures that MRD can be detected with both high sensitivity and specificity, reliably detecting variants down to 0.01% variant allele frequency.…”

Section: Discussionmentioning

confidence: 99%

“…identify patients at risk for recurrence has been limited by small cohorts and varying assays and time points, although data published to date suggest feasibility. [19][20][21][22][23][24] Beyond the immediate postcurative-intent setting, ctDNA may also be useful for serial surveillance purposes. Hypothetically, earlier detection of recurrence can lead to earlier intervention, leading to improved outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers

Huffman

Aushev

Budde

et al. 2022

JCO Precision Oncology

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PURPOSE Circulating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent. METHODS In this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction–based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival. RESULTS A total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes. CONCLUSION Using real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers

Huffman

Aushev

Budde

et al. 2022

JCO Precision Oncology

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“…ctDNA studies in resectable GC have recently been reported. Wo et al [20] found that detectable ctDNA after chemoradiation and postoperatively was associated with disease recurrence. However, their ctDNA analysis was based on digital PCR, which limits the number of mutations that can be tested.…”

Section: Discussionmentioning

confidence: 99%

Liquid biopsy: circulating tumor DNA monitors neoadjuvant chemotherapy response and prognosis in stage II/III gastric cancer

Zhang

Yang

et al. 2023

Molecular Oncology

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A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II–III GC. Seventy‐nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2‐lymphadenectomy. Plasma at baseline, post‐NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425‐gene panel to detect genomic alterations (GAs). Results show that the mean cell‐free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL−1 vs 14.40 ng·mL−1). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post‐NACT, and postsurgery). The maximum variant allele frequency (max‐VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max‐VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3‐year OS was 73% for the post‐NACT ctDNA‐negative patients and 34% for ctDNA‐positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II–III GC patients.

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“…In this regard, monitoring tumor dynamics with ctDNA during and after NAT has great potential because it could guide post-NAT management in several ways, including escalation/de-escalation of NAT or adjuvant therapy; delaying or omitting surgery ("watch-and-wait" or non-operative management [NOM]). In fact, positive ctDNA MRD during or after NAT was associated with an increased recurrence risk in locally advanced breast, rectal, gastric/gastroesophageal, and esophageal cancer, as well as in resectable CRC liver metastases, and even outperformed imaging in a few studies [86][87][88][89][90][91][92][93][94][95][96][97][98][99][100]. Recent randomized CheckMate-816 and I-SPY 2 are representative studies demonstrating the potential utility of ctDNA in NAT [90,101].…”

Section: Treatment Monitoring During Neoadjuvant Treatmentmentioning

confidence: 99%

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

Cha¹,

Kim²,

Han³

2023

Cancer Res Treat

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Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

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Results and Molecular Correlates from a Pilot Study of Neoadjuvant Induction FOLFIRINOX Followed by Chemoradiation and Surgery for Gastroesophageal Adenocarcinomas

Cited by 13 publications

References 58 publications

Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers

Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers

Liquid biopsy: circulating tumor DNA monitors neoadjuvant chemotherapy response and prognosis in stage II/III gastric cancer

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers

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