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Purpose: Prognostic tools to estimate the risk of relapse for patients with liver-limited metastatic colorectal cancer (LL-mCRC) undergoing resection with curative intent are needed. Circulating tumor DNA (ctDNA) as a surrogate of postsurgical minimal residual disease is a promising marker in localized CRC. We explored the role of postoperative ctDNA as a marker of minimal residual disease in patients with radically resected LL-mCRC., Materials and Methods: Seventy-six patients with LL-mCRC were retrospectively included. DNA from tumor tissue was sequenced, and one somatic mutation was then assessed by digital droplet polymerase chain reaction in plasma samples collected after surgery to identify the persistence of ctDNA. Relapse-free survival and postresection overall survival were compared between patients with positive vs negative postoperative ctDNA., Results: ctDNA was found in 39 (51%) of 76 patients with LL-mCRC. At a median follow-up of 77 months, 33 of 39 ctDNA-positive patients and 20 of 37 ctDNA-negative patients experienced disease relapse ( P = .008). ctDNA-positive patients reported significantly shorter RFS than ctDNA-negative ones (median RFS 12.7 v 27.4 months hazard ratio, 2.09, P = .008). In the multivariable model including other prognostic covariates, this association was still significant ( P = .046) and a trend toward shorter overall survival among ctDNA-positive patients was reported (hazard ratio, 1.65, P = .183)., Conclusion: The detection of postsurgical ctDNA is an independent negative prognostic marker and identifies patients at high risk of relapse after liver metastases resection., Competing Interests: Paolo MancaPatents, Royalties, Other Intellectual Property: I have a patent for a method for the identification of gene panels optimal for TMB estimation (Inst) Romano DanesiHonoraria: Lilly, EUSA Pharma, Novartis Italy, Seattle Genetics, GENTILI, AstraZeneca, GlaxoSmithKline Gianluca MasiConsulting or Advisory Role: AstraZeneca, Eisai, MSD OncologyPatents, Royalties, Other Intellectual Property: Terumo (Inst) Marzia Del ReConsulting or Advisory Role: Sanofi, Celgene, Janssen-Cilag, Ipsen, Roche Molecular DiagnosticsSpeakers' Bureau: Sanofi, Pfizer, Novartis, Janssen-Cilag, Ipsen, AstraZeneca, Astellas Pharma, Roche, MSD Oncology Filippo PietrantonioHonoraria: Servier, Bayer, AstraZeneca/MedImmune, Lilly, Sanofi, MSD Oncology, AmgenConsulting or Advisory Role: Amgen, Servier, MSD Oncology, organonResearch Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst) Chiara CremoliniHonoraria: Roche, Amgen, Bayer, Servier, MSD, Merck, Pierre Fabre, OrganonConsulting or Advisory Role: Roche, Bayer, Amgen, MSD, Pierre Fabre, Nordic PharmaSpeakers' Bureau: Servier, Merck, Pierre FabreResearch Funding: Merck, Bayer, Roche, ServierNo other potential conflicts of interest were reported.

Purpose: In GI cancers, anaplastic lymphoma kinase ( ALK ) rearrangements are extremely less frequent than in non-small-cell lung cancer but may be important to offer personalized strategies of treatment in selected patients. Data about the activity and efficacy of ALK inhibitors (ALKi) in GI cancers are scarce., Materials and Methods: We assembled a clinical and molecular international data set of pretreated patients with metastatic or nonresectable cancers of GI primary tumor origin with documented ALK rearrangement treated with at least one line of ALKi. Measurable disease as per RECIST 1.1 was required for response analysis., Results: Primary tumor sites were distributed as follows: 5 (38%) pancreas, 3 (23%) right colon, and 1 (8%) for each one of gastric, duodenal, rectal, left colon, and biliary tract sites. Seven patients (54%) were treated with alectinib, 5 (38%) with crizotinib, and 1 (8%) with entrectinib. After disease progression, five patients (38%) received a subsequent ALKi treatment line, and at the time of data cutoff date, treatment was still ongoing in two patients. Five of 12 evaluable patients (41%) achieved a partial response to first-line ALKi, five patients (41%) had stable disease, and 2 (17%) had progressive disease. No complete responses were registered. At a median follow-up of 39.6 months (interquartile range: 19.8-59.5), the median progression-free survival was 5.0 months (95% CI, 3.68 to no response) and the median overall survival was 9.3 months (95% CI, 5.46 to no response)., Conclusion: Treatment with ALKi provides remarkable responses and clinical benefit in pretreated patients with ALK fusion-positive GI malignancies. Despite the rarity, ALK rearrangements represent an important therapeutic target in individual pretreated patients with GI solid tumors. Further work providing prospective clinical validation of this target is needed., Competing Interests: Marzia Del ReConsulting or Advisory Role: Sanofi, Celgene, Janssen-Cilag, Ipsen, Roche Molecular DiagnosticsSpeakers' Bureau: Sanofi, Pfizer, Novartis, Janssen-Cilag, Ipsen, AstraZeneca, Astellas Pharma, Roche, MSD Oncology Paolo MancaPatents, Royalties, Other Intellectual Property: I have a patent for a method for the identification of gene panels optimal for TMB estimation (Inst) Andrew HendifarConsulting or Advisory Role: Novartis, Ipsen, Perthera, Celgene, AbbVie, EisaiResearch Funding: Ipsen, NGM Biopharmaceuticals (Inst)Travel, Accommodations, Expenses: HalozymeOther Relationship: FibroGen Alexander DrilonHonoraria: Pfizer, Loxo/Bayer/Lilly, IASLCConsulting or Advisory Role: Ignyta, Loxo, AstraZeneca, Pfizer, Blueprint Medicines, Genentech/Roche, BeiGene, Hengrui Therapeutics, Exelixis, Bayer, Tyra Biosciences, Takeda/Millennium, BerGenBio, MORE Health, Lilly, AbbVie, 14ner Oncology/Elevation Oncology, Monopteros Therapeutics, Novartis, EMD Serono/Merck, Repare Therapeutics, Melendi, Archer, Nuvalent Inc, Janssen, Amgen, Merus, Axis Pharma, Medscape, Liberum, Med Learning, PeerView, EPG Health, JNCCN/Harborside, Ology, Clinical Care Options, touchIME, Entos, Treeline, Prelude Therapeutics, Applied Pharmaceutical Science IncSpeakers' Bureau: Helsinn Therapeutics, Beigene, Remedica Ltd, TP Therapeutics, Verastem, Ignyta/Genentech/Roche, AstraZeneca, Liberum, Loxo/Bayer/Lilly, Lungevity, NIH, PER, OncLive/MJH Life Sciences, Clinical Care Options/NCCN, Lung Cancer Canada, AIOT, Chugai Pharma, Chugai Pharma, Sirio Libanes Hospital, Answers in CME, Faculty RTP, RV MoreResearch Funding: Foundation MedicinePatents, Royalties, Other Intellectual Property: Wolters Kluwer (Royalties for Pocket Oncology)Other Relationship: Merck, GlaxoSmithKline, Teva, Taiho Pharmaceutical, Pfizer, PharmaMar, Puma Biotechnology, Merus, Boehringer Ingelheim Guilherme HaradaSpeakers' Bureau: MSD, AstraZeneca, Pfizer Anne Hansen ReeHonoraria: MSD Oncology, BMSiResearch Funding: BMSi (Inst) Samuel KlempnerStock and Other Ownership Interests: TP Therapeutics, Nuvalent IncHonoraria: NateraConsulting or Advisory Role: Lilly, Astellas Pharma, Bristol Myers Squibb, Pieris Pharmaceuticals, Merck, Daiichi Sankyo/UCB Japan, Sanofi/Aventis, MersanaResearch Funding: Leap Therapeutics (Inst), BeiGene (Inst), Silverback Therapeutics (Inst)Other Relationship: NCCN Gunhild Mari MælandsmoPatents, Royalties, Other Intellectual Property: Patent application submitted for a nine-protein/gene panel predicting response to anti VEGF therapies in combination with chemotherapy (Inst) Hege G. RussnesHonoraria: AstraZeneca (Inst), Pfizer (Inst), InCyte (Inst), Merck (Inst), Roche (Inst)Research Funding: Foundation Medicine (Inst) James M. ClearyHonoraria: Blueprint Medicines, Syros PharmaceuticalsConsulting or Advisory Role: Bristol Myers SquibbResearch Funding: Merck, Tesaro, AstraZeneca, Esperas Pharma, AbbVie (Inst), Merus (Inst), Roche/Genentech (Inst), BMS (Inst)Travel, Accommodations, Expenses: Roche, Agios, Bristol Myers Squibb Andrea Sartore-BianchiConsulting or Advisory Role: Amgen, Bayer, Sanofi, Servier, Novartis Maria Di BartolomeoHonoraria: Lilly, MSD Oncology, Servier, BMSiConsulting or Advisory Role: Lilly, MSD OncologyResearch Funding: LillyTravel, Accommodations, Expenses: Roche, Sanofi Filippo PietrantonioHonoraria: Servier, Bayer, AstraZeneca/MedImmune, Lilly, Sanofi, MSD Oncology, AmgenConsulting or Advisory Role: Amgen, Servier, MSD Oncology, MerckResearch Funding: Bristol Myers Squibb (Inst), Astrazeneca (Inst)No other potential conflicts of interest were reported.