Precision oncotherapy based on liquid biopsies in multidisciplinary treatment of unresectable recurrent rectal cancer: a retrospective cohort study

Abstract

Background Third line innovative systemic treatments and loco-regional chemotherapy by hypoxic pelvic perfusion (HPP) have both been proposed for the treatment of unresectable not responsive recurrent rectal cancer (URRC). In the present study, we have compared the safety and efficacy of HPP/target therapy, using drug regimens selected by liquid biopsy precision oncotherapy, to third-line systemic therapy based on tissue specimens precision oncotherapy. Methods HPP/target therapy regimens were selected based on precision oncotherapy, including assays for chemosensitivity and viability, and qRT-PCR for tumor-related gene expression. In the control group, systemic third-line and further lines of therapy were defined according to clinical and biological parameters. Results From 2007 to 2019, 62 URRC patients were enrolled, comprised of 43 patients in the HPP/target-therapy group and 19 patients in the systemic therapy control group. No HPP related complications were reported and the most common adverse events were skin and bone marrow toxicity. In the HPP/target-therapy group, the ORR was 41.8% whereas in the systemic therapy control group was 15.8%. DCR of the HPP/target-therapy group was significantly improved over the systemic therapy group (P = 0.001), associated with a PFS of 8 vs 4 months (P = 0.009), and OS of 20 vs 8 months (P = 0.046). Conclusions The present data indicate that in URCC patients, the integration of HPP/target-therapy and precision oncotherapy based upon liquid biopsy is as effective and efficacious as third-line treatment in local disease control and, therefore, deserves to be further assessed and compared to conventional systemic treatments in future prospective randomized trials.

Real-life multidisciplinary treatment for unresectable colorectal cancer liver metastases including hepatic artery infusion with chemo-filtration and liquid biopsy precision oncotherapy: observational cohort study

“…The small-sample size (18 patients) in the latter study and failure to report prior first-and second-line systemic chemotherapeutic regimens in both studies, however, limit further discussion of the impressive 20.6-month OS in Peking University Cancer Hospital study (Guo et al 2017). The current study, however, should not be compared to our previous TACE studies, which were performed without chemo-filtration on patients with and without unresected primary tumours, in progression after a single line of systemic therapy (Fiorentini et al 2017b(Fiorentini et al ,2018(Fiorentini et al ,2020.…”

“…Liquid biopsy precision oncotherapy, chemosensitivity, and tumor cell gene expression assays have all been described previously (Guadagni et al 2020;Apostolou et al 2013Apostolou et al , 2017Apostolou et al ,2019. Briefly, for each patient, 20 mL of blood were collected in sterile 50 ml Falcon tubes (4440100, Orange Scientific, Braine-l'Alleud, Belgium), containing 7 ml of 0.02 M EDTA anticoagulant (E0511.0250, Duchefa Biochemie B.V., Haarlem, The Netherlands), stored at 2-8 °C in impact-resistant transportation containers to ensure the stability and viability of circulating tumor cells (CTCs), and analyzed within 80 h for the presence of > 5 viable circulating tumor cells (CTCs) per ml (Apostolou et al 2017).…”

“…Drug regimens in the HAI/target-therapy cohort (44 patients) were selected according to the published criteria (Guadagni et al 2020) and are reported in Table 2. Irinotecan, 5-fluorouracil, oxaliplatin, and mitomycin were…”

A Pilot Study of the Predictive Potential of Chemosensitivity and Gene Expression Assays Using Circulating Tumour Cells from Patients with Recurrent Ovarian Cancer

“…Recently, we reported a method for liquid biopsy predictive oncotherapy based upon purified metastatic CTCs, transiently cultured in vitro, permitting both gene expression profile and chemosensitivity analysis [38][39][40]. Here, we report a pilot study of metastatic CTCs purified from a homogeneous group of stage IIIC and IV EOC patients, presenting with disease relapse in progression after surgery and two lines of systemic chemotherapy, submitted for locoregional HAP chemotherapy, with the aim of confirming the feasibility and utility of assessing chemosensitivity and biological characterisation of liquid biopsies-derived purified CTCs, as a predictive test for selecting appropriate drugs for HAP and for further therapeutic strategies.…”

Circulating tumour cell liquid biopsy in selecting therapy for recurrent cutaneous melanoma with locoregional pelvic metastases: a pilot study

“…For these reasons, we believe that treatment strategies for pelvic locoregional metastases should be multidisciplinary and could benefit greatly from the detailed characterisation of biomolecular characteristics and relative chemosensitivity of metastatic melanoma cells, a possibility that is offered by liquid biopsies, using purified circulating tumour cells (CTCs) obtained from individual patients. This method has been approved for prognosis by USA Food and Drug Administration [23] and despite a lack of methodological consensus, is under investigation as a potential method for identifying therapeutic strategies for cancers, including melanoma [24][25][26].…”