Disease Monitoring Using Post-induction Circulating Tumor DNA Analysis Following First-Line Therapy in Patients with Metastatic Colorectal Cancer

Max, Xiaoju; Bendell, Johanna C.; Hurwitz, Herbert I.; Ju, Christine; Lee, John J.; Lovejoy, Alex; Mancao, Christoph; Nicholas, Alan; Price, Richard; Sommer, Nicolas; Tikoo, Nalin; Yao, Lijing; Yaung, Stephanie J.; Palma, John F.

doi:10.1158/1078-0432.ccr-19-1209

Cited by 23 publications

(19 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In induction strategies where mCRC patients are treated with triplet chemotherapy or alternating oxaliplatin-and irinotecan-based chemotherapy followed by maintenance fluoropyrimidine, lower ctDNA MAFs post-induction (collected ≤60 days after the 4-6-month induction) were associated with longer median PFS [134].…”

Section: Response To Systemic Therapymentioning

confidence: 99%

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Gong

Hendifar

Gangi

et al. 2021

Cancers

View full text Add to dashboard Cite

Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I–III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I–III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.

show abstract

Section: Response To Systemic Therapymentioning

confidence: 99%

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Gong

Hendifar

Gangi

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…In previous reports on early ctDNA dynamics during chemotherapy in other cancer types, tumor responses were evaluated 8–12 weeks after the start of treatment by image diagnoses according to RECIST (10,13,16,17). To supplement these reports in other malignancies, this study examined the difference between early dynamics of tumor volume by ellipsoidal approximation and ctDNA after an initial cycle of chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Analyses of circulating tumor DNA (ctDNA) levels have demonstrated promising results for predictions of relapses and evaluations of treatment efficacy in patients with several cancer types (8-12). Several reports also demonstrated that early ctDNA dynamics could predict later chemotherapy responses, progression-free survival rates, and overall-survival (OS) rates in some cancer types (10,13-17). However, the methodology used to evaluate ctDNA changes and tumor responses varied by tumor type.…”

Section: Introductionmentioning

confidence: 99%

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

Fujisawa

Iwaya

Endo

et al. 2021

Preprint

View full text Add to dashboard Cite

Purpose: We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). Design: We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses were evaluated by the ratio of the variant allele frequency (VAF) of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50% or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Results: Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1-3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 90% (18/20) of patients with a post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 vs 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Conclusions: Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

show abstract

“…There are two hypotheses about the biological mechanism of coexisting mutations: one is the hypothesis of polyclonal origin, whereby there is heterogeneity between tumours [12], and there may be two tumour cells carrying EGFR mutations or ALK rearrangements in the same tumour tissue; the other is the hypothesis of monoclonal origin [13], wherein tumour cells carry EGFR mutations and ALK rearrangements at the same time.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of ALK rearrangement in lung adenocarcinoma harbouring EGFR mutation: Real-World Data From a Single-Institution Experience

Zhong

Wei

2021

Preprint

View full text Add to dashboard Cite

Background Concomitance of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have been increasingly reported in lung adenocarcinoma (LUAD). However, the biological mechanism, clinicopathological features and optimization of targeted drugs remain unclear. This study aimed to explore the clinicopathological characteristics of coexisting mutations of EGFR and ALK genes in LUAD patients, with hopes of scientifically guiding such patients towards selected, targeted drugs. Methods Two hundred and thirty-seven cases of LUAD were enrolled. Mutations in exons 18, 19, 20 and 21 of the EGFR gene were detected by the amplification refractory mutation system-peptide nucleic acid (ARMS-PNA) technique, while expression of the ALK fusion gene was detected by the 5′/3′ imbalance strategy for reverse transcription, followed by quantitative polymerase chain reaction (RT–qPCR) analysis. The clinicopathological features of patients with coexisting mutations of EGFR and ALK genes were analysed retrospectively, and the follow-up data of these patients were collected. Results There were 6 cases with coexisting mutations of EGFR and ALK genes, which were more common in women, non-smoking and stage IV LUAD with bone metastasis, hence a positive rate of 2.53% (6/237). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were the first choice for targeted therapy in patients with LUAD harbouring coexisting mutations of EGFR and ALK genes in Gannan region, and the progression-free survival (PFS) was between 2-6 months. Conclusions These results indicated that the positive rate of coexisting mutations of EGFR and ALK genes in LUAD patients in the Gannan region was relatively high; these genes were more common in women, non-smokers and stage IV patients with bone metastasis. EGFR-TKIs were the first choice for targeted therapy in these patients, but the therapeutic effect was limited. EGFR-TKI combined with ALK-TKI dual targeted therapy may be a more effective treatment.

show abstract

Disease Monitoring Using Post-induction Circulating Tumor DNA Analysis Following First-Line Therapy in Patients with Metastatic Colorectal Cancer

Abstract: are employees of and own stock in Roche/Genentech.

Cited by 23 publications

References 23 publications

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

Coexistence of ALK rearrangement in lung adenocarcinoma harbouring EGFR mutation: Real-World Data From a Single-Institution Experience

Contact Info

Product

Resources

About