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1.
Clin Transl Radiat Oncol ; 36: 9-15, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35733829

RESUMO

Background: The watch and wait (W&W) strategy is proposed for patients with locally advanced rectal cancer (LARC) achieving clinical complete response (cCR) after neoadjuvant radiotherapy. cCR is only in partial concordance with pathological complete response (pCR) due to persisting viable tumour cells. The aim was to investigate circulating-free-deoxyribonucleic-acid (cfDNA) as a biomarker for prediction of pCR. Materials and methods: Patients treated with neoadjuvant radiotherapy for LARC, were included in a prospective biomarker study in Aarhus, Denmark from 2017 to 2020. Plasma cfDNA levels were analysed by a direct fluorescent assay (DFA). Surgical specimens were reviewed by pathologists to categorize response to cytotoxic therapy. Results: In total, 76 patients were included with plasma available at baseline (n = 70), mid therapy (n = 50), and end of therapy (n = 54). Higher cfDNA levels were observed in LARC patients compared with healthy subjects (p < 0.01). By ROC analysis (AUC: 0.87 (95% CI, 0.81-0.92)) the optimal cut-off was 0.71 ng/µL for differentiation between healthy subjects and LARC patients. Thirteen patients obtained pCR with a median cfDNA level of 0.57 ng/µL at end of therapy. Patients with cfDNA levels at end of therapy below the cut-off (p < 0.02) and 'cfDNA responders' with descending levels greater than the 75th percentile during therapy had a significantly higher chance of pCR (p < 0.01). Conclusion: This hypothesis generating study indicates that low cfDNA levels at end of treatment or ´cfDNA responders might be associated with pCR. Quantification of cfDNA by the rapid and feasible DFA analysis could potentially facilitate personalized follow-up as a complementary tool to identify candidates for a W&W strategy.

2.
Cancer Med ; 10(10): 3224-3230, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33960701

RESUMO

BACKGROUND: First-line platinum-based therapy for advanced squamous cell carcinomas of the anal canal (SCCA) implies a risk of substantial side effects, and data on second-line treatment options are limited. Paclitaxel and Capecitabine are a well-known regimen with a moderate toxicity profile, but its efficacy has not been evaluated. METHODS: We conducted a retrospective study using Danish Hospital Registers of patients treated with Paclitaxel and Capecitabine for inoperable, recurrent, or advanced metastatic SCCA in Denmark, between January 2000 and July 2018. RESULTS: A total of 52 patients met the eligibility criteria. Median age was 60.7 years (range 42-83). Efficacy was observed, with an overall response rate in patients receiving first-line (N = 28) and second-line (N = 23) Paclitaxel and Capecitabine of 39.3% (2 with complete responses) and 17.4%, respectively. Median progression-free survival (PFS) was 4.5 months (95% CI 3.3-5.9) and 3.8 months (95% CI 2.4-5.5) with OS of 6.7 months (95% CI 5.9-8.5) and 5.9 months (95% CI 3.9-14), respectively. Performance status ≥2 and neutrophil to lymphocyte ratio ≥4 were significantly associated with a short PFS. CONCLUSION: This study recognizes Paclitaxel and Capecitabine as a potential regimen for advanced SCCA, when recommended first-line therapy is not feasible or as a potential second-line treatment after failure of platinum-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Capecitabina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Canal Anal/efeitos dos fármacos , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Progressão , Estudos Retrospectivos
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