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Case Reports
. 2021 Jul 21:5:PO.21.00143.
doi: 10.1200/PO.21.00143. eCollection 2021 Jul.

Empowering Clinical Decision Making in Oligometastatic Colorectal Cancer: The Potential Role of Drug Screening of Patient-Derived Organoids

Gianluca Mauri  1   2   3 , Erika Durinikova  4 , Alessio Amatu  1 , Federica Tosi  1 , Andrea Cassingena  1 , Francesco Rizzetto  1 , Kristi Buzo  4 , Pamela Arcella  4   5 , Maria Costanza Aquilano  1 , Emanuela Bonoldi  1 , Silvia Marsoni  3 , Salvatore Siena  1   2 , Alberto Bardelli  4   5 , Andrea Sartore-Bianchi  1   2 , Sabrina Arena  4   5
Affiliations
Case Reports

Empowering Clinical Decision Making in Oligometastatic Colorectal Cancer: The Potential Role of Drug Screening of Patient-Derived Organoids

Gianluca Mauri et al. JCO Precis Oncol. .
No abstract available

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Conflict of interest statement

Alessio Amatu Honoraria: CheckmAb Consulting or Advisory Role: Roche, Bayer Silvia Marsoni Consulting or Advisory Role: Ellipses Pharma, Axiom Healthcare Strategies Salvatore Siena Stock and Other Ownership Interests: Guardant Health, Myriad Genetics Consulting or Advisory Role: Amgen, Roche/Genentech, Bayer, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Seattle Genetics, CheckmAb Research Funding: MSD Oncology Patents, Royalties, Other Intellectual Property: Amgen Travel, Accommodations, Expenses: Amgen, Bayer, Roche Alberto Bardelli Stock and Other Ownership Interests: Neophore Honoraria: Illumina, Guardant Health, Inivata Consulting or Advisory Role: Neophore, Inivata Research Funding: Neophore, AstraZeneca, Boehringer Ingelheim Andrea Sartore-Bianchi Consulting or Advisory Role: Amgen, Bayer, Sanofi, Servier Sabrina Arena Consulting or Advisory Role: MSD Italia No other potential conflicts of interest were reported.Alessio Amatu Honoraria: CheckmAb Consulting or Advisory Role: Roche, Bayer Silvia Marsoni Consulting or Advisory Role: Ellipses Pharma, Axiom Healthcare Strategies Salvatore Siena Stock and Other Ownership Interests: Guardant Health, Myriad Genetics Consulting or Advisory Role: Amgen, Roche/Genentech, Bayer, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Seattle Genetics, CheckmAb Research Funding: MSD Oncology Patents, Royalties, Other Intellectual Property: Amgen Travel, Accommodations, Expenses: Amgen, Bayer, Roche Alberto Bardelli Stock and Other Ownership Interests: Neophore Honoraria: Illumina, Guardant Health, Inivata Consulting or Advisory Role: Neophore, Inivata Research Funding: Neophore, AstraZeneca, Boehringer Ingelheim Andrea Sartore-Bianchi Consulting or Advisory Role: Amgen, Bayer, Sanofi, Servier Sabrina Arena Consulting or Advisory Role: MSD Italia No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Radiologic evidence of response following FOLFOX plus panitumumab and FOLFIRI plus panitumumab. (A) The venous phase of the baseline CT scan performed in July 2018 showed a large hypodense lesion in (arrow) segment VIII of the liver. (B) Following four cycles of treatment with FOLFOX and panitumumab, at CT scan performed on November 2018, a partial response (shrinkage of the longest lesion's diameter from 38 to 20 mm) of the hepatic lesion in (arrow) segment VIII was observed as well. (C) The venous phase of the CT scan performed in October 2019 demonstrated liver relapse of disease with three new hypodense lesions with peripheral rim enhancement in segment VII, segments V-VIII, and (not visible) segment V. (D) After six cycles of FOLFIRI and panitumumab, the CT scan performed in January 2020 showed a decrease in lesions' size: segment V decrease by 50% (from 12 to 6 mm), segments V-VIII by 37% (from 19 to 12 mm), and segment VII by 33% (from 18 to 12 mm). All lesions were evaluated as per RECIST1.1 criteria. (E) Bar graph summarizes the best RECIST1.1 response to both first-line treatment with FOLFOX plus panitumumab (–45%) and second-line treatment with FOLFIRI plus panitumumab (–39%). CT, computed tomography; Pmab, panitumumab.
FIG 2.
FIG 2.
Patient's oncologic history timeline and histopathologic analysis of the metastatic lesion and of the PDOs. In the light blue background, representative hematoxylin and eosin images from the metastatic lesion recovered in March 2018 (top panels) and from the organoids derived from this lesion (lower panels) are given. Furthermore, the table in the light blue background depicts molecular alterations found in genes that are known to play a key role in colorectal cancer development and are recommended by clinical guidelines to define patients' treatment. Data were obtained from the NGS panel (FoundationOne CDx) performed according to GO40782 clinical trial (NCT02568267) screening on archival patient's left-sided primary tumor tissue and from the WES performed on PDOs. 5-FU, fluorouracil; Lancet, surgical procedure; MMR, mismatch repair status; MSS, microsatellite stable; NGS, next-generation sequencing; PDOs, patient-derived organoids; Pmab, panitumumab; PR, partial response; red circle, best response at computed tomography scan disease reassessment; WES, whole-exome sequencing.
FIG 3.
FIG 3.
Patient-derived organoids show different profiles of sensitivity to cytotoxic drugs and targeted treatment. (A) Representative bright-field microscopy images of organoids derived from the oligometastatic patient treated with OXA and 5-FU for 12 days and with SN-38 and panitumumab for 7 days. MG-132 was used as a positive control for organoids' death (data not shown), and DMSO or DMEM/F12 served as a negative control. Magnification: 10×. (B) At the end of the treatment, organoids' viability was measured by the CellTiter GLO assay and numbers were analyzed using GraphPad software. The results are the average of at least two independent experiments with technical quadruplicates. Error bars represent the standard deviation among biologic replicates. Z factor values varied between 0.73 and 0.91. ctrl, control; 5-FU, fluorouracil; OXA, oxaliplatin; Pmab, panitumumab.
FIG A1.
FIG A1.
The response of patient-derived organoids to the anti-EGFR monoclonal antibody cetuximab. (A) Representative bright-field microscopy images of organoids treated with cetuximab for 7 days. MG-132 was used as a positive control for organoids' death (data not shown), whereas DMEM/F12 medium served as a negative control. Magnification: 10×. (B) At the end of the treatment, organoids' viability was measured by the CellTiter GLO assay and viability values were analyzed using GraphPad software. The results are the average of three independent experiments with technical quadruplicates, and error bars represent the standard deviation among biologic replicates. Z factor values varied between 0.75 and 0.82. Cmab, cetuximab; ctrl, control.
See this image and copyright information in PMC

References

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