Unresectable Liver Metastases Research Articles

Abstract CT213: Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

Abstract Background Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without progressive disease (PD) and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints were duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), time to response (TTR), depth of response (DpR), radical resection rate for LMs, and safety. Results As of November 13, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 38 evaluable patients in cohort C, 16 had partial response (PR), 17 had stable disease (SD) and 14 SD with reduced tumor size. The ORR was 42.1%, DCR was 86.8%. Of 26 evaluable pancreatic cancer patients, ORR and DCR were 42.3% (11/26) and 88.5%(23/26) respectively. 11 PRs and 10 SD- were observed with the median depth of response (DpR) of 37.6%. According to the Kaplan-Meier method, the median DoR was 4.1 (95%CI, 3.5-4.6) months and PFS was 5.8 (95%CI, 5.2-6.3) months. The median TTR was 1.7 (range, 0.8-3.5) months. 39 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (53.7%) mainly included neutropenia (19.5%), white blood cell decreased (14.6%), and blood platelet decreased (9.8%). Conclusions Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335. Citation Format: Junwei Wu, Chenfei Zhou, Jun Yan, Zhengxiang Han, Chun Wang, Zhiquan Qin, Jinling Jiang, Chunbin Wang, Xinyu Tang, Lingjun Zhu, Jun Chen, Yong Mao, Xiaowei Wei, Chengfang Shangguan, Jun Zhang. Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT213.

Liver Transplantation for Unresectable Colorectal Liver Metastasis: Perspective and Review of Current Literature.

The treatment of unresectable colorectal liver metastasis (CRLM) has previously been limited to palliative chemotherapy. Traditionally, the role of liver transplant has not been associated with sufficient survival to justify a patient undergoing a major operation with the associated requirement for postoperative immunosuppression. With improvements in chemotherapy options, a certain subset of patients can experience stable disease for years, which has prompted investigation into the role of liver transplant in these patients. Several recent studies have shown promising results in well-selected patients, with posttransplant survival approaching that of liver transplant recipients for other diseases. Here, we present a review of the data and current protocols for liver transplant for unresectable CRLM.

Lung Mean Dose Prediction in Transarterial Radioembolization (TARE): Superiority of [166Ho]-Scout Over [99mTc]MAA in a Prospective Cohort Study

PurposeRadiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([166Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([99mTc]MAA) or [166Ho]-microspheres. The accuracy of eLMD based on [99mTc]MAA (eLMDMAA) was compared to eLMD based on [166Ho]-scout dose (eLMDHo-scout) in two prospective clinical studies.Materials and MethodsPatients were included if they received both scout doses ([99mTc]MAA and [166Ho]-scout), had a posttreatment [166Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMDMAA/eLMDHo-scout and LMDHo-treatment was assessed by Spearman’s rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data.ResultsThirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMDMAA (1.53 Gy, range 0.09–21.33 Gy) was significantly higher than median LMDHo-treatment (0.00 Gy, range 0.00–1.20 Gy; p < 0.01). Median eLMDHo-scout (median 0.00 Gy, range 0.00–1.21 Gy) was not significantly different compared to LMDHo-treatment (p > 0.05). In all cases, eLMDMAA was higher than LMDHo-treatment (p < 0.01). While a significant correlation was found between eLMDHo-scout and LMDHo-treatment (r = 0.43, p < 0.01), there was no correlation between eLMDMAA and LMDHo-treatment (r = 0.02, p = 0.90).Conclusion[166Ho]-scout dose is superior in predicting LMD over [99mTc]MAA, in [166Ho]-radioembolization. Consequently, [166Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization.Trail registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012.Graphical

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from multi-cohort, multi-center phase II trial ALTER-G-001-cohort A.

112 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs). The prognosis of CRC with unresectable LMs is poor, with a 5-year survival rate of less than 5%. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, etc.). In cohort A, CRC patients received induction therapy (6 cycles, q3w): anlotinib (12 mg, PO, QD, days 1-14), oxaliplatin (130 mg/m2, IV, day 1), capecitabine (850 mg/m2, PO, BID, days 1-14). Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 45 patients were enrolled in cohort A, the median age was 67 years (35-75), 66.7% male, 91.1% ECOG-PS 1 and 60% had LMs only. After induction therapy, 8 patients received surgical resection. Currently, 13 patients are receiving induction therapy and 10 are undergoing maintenance therapy, with a maximum duration of treatment (DOT) of 13.7 months. Of 39 evaluable patients in cohort A, ORR and DCR were 48.7% and 97.4% (PR, n=19; SD, n=19, 16 SD had reduced tumor size). The median PFS was not reached. 36 patients had TEAEs and ≥ grade 3 TEAEs (33.3%) mainly included neutropenia (11.1%), hypertension (6.7%), and white blood cell decreased (6.7%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs CRC tumors. Clinical trial information: NCT05262335 .

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C.

653 Background: Advanced gastrointestinal (GI) tumors, such as colorectal, gastric and pancreatic cancers (CRC, GC, and PC), and esophageal squamous cell carcinoma (ESCC), 20%-50% with liver metastases (LMs) have a poor prognosis. Previous trials showed that anlotinib plus chemotherapy has promising clinical activity and a tolerable safety profile for advanced CRC and ESCC, especially with LMs. In this phase II trial, we assessed the efficacy and safety of anlotinib plus chemotherapy as first-line treatment for LMs GI tumors. Methods: Patients with unresectable LMs GI tumors and without previous systemic treatment would be divided into cohort A (CRC), cohort B (ESCC), and cohort C (other GI tumors, such as PC, GC, biliary tract cancer (BTC), etc.). In cohort C, patients received induction therapy: anlotinib plus standard chemotherapy. Patients without PD and radical resection received anlotinib and metronomic capecitabine (500 mg, PO, BID, days 1-21, q3w) maintenance until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints were DoR, PFS, OS, DCR, radical resection rate for LMs, and safety. Results: As of September 14, 2023, 41 patients were enrolled in cohort C (29 PC, 6 GC, 5 BTC, and others), the median age was 64 years (34-74), 63.4% male, 92.7% ECOG-PS 1 and 56.1% had LMs only. The majority of the pancreatic cancer patients (26/29) received gemcitabine plus nab-paclitaxel chemotherapy combination with anlotinib as induction therapy. After induction therapy, 4 patients (1 PC, 2 GC, 1 BTC) received surgical resection. Of 37 evaluable patients in cohort C, ORR and DCR were 45.9% and 86.5% (PR, n=17; SD, n=15, 12 SD had reduced tumor size). Of 25 evaluable pancreatic cancer patients, 12 had PR, 10 had SD, ORR and DCR were 48% and 88%. According to the Kaplan-Meier method, the median DoR was 4.2 months (95%CI, 1.7-6.6) and the median PFS was 5.5 months (95%CI, 4.7-6.3). 37 patients in cohort C had TEAEs and ≥ grade 3 TEAEs (51.2%) mainly included neutropenia (19.5%), white blood cell decreased (12.2%), and blood platelet decreased (9.8%). Conclusions: Anlotinib plus chemotherapy as first-line treatment has shown promising efficacy and acceptable safety and maybe a favorable option for advanced LMs GI tumors, especially for pancreatic cancer. Clinical trial information: NCT05262335 .

Efficacy and Safety of Liver Chemoembolization Procedures, Combined with FOLFIRI Chemotherapy, in First-Line Treatment of Metastatic Colorectal Cancer in Patients with Oncogene Mutations.

The usual first- and second-line treatments for inoperable liver metastases from colorectal cancer (CRC) involve systemic chemotherapy, often with molecular targeted therapy. Chemoembolization, using microspheres loaded with irinotecan, has also been available as a treatment option for many years, used mainly in later lines of treatment when, due to increasing resistance, other chemotherapy regimens may have been exhausted. However, when there are contraindications to molecular therapies, the use of chemoembolization as first or second lines of treatment, in combination with FOLFIRI chemotherapy, may provide greater efficacy due to reduced irinotecan resistance. The aim of the study was to evaluate the efficacy and safety of transarterial chemoembolization (DEB-TACE) procedures for the treatment of metastatic liver lesions from CRC, using irinotecan-loaded microspheres as first-line treatment together with FOLFIRI chemotherapy. The analysis included 20 patients (12 females; 8 males) with unresectable liver metastases in the course of CRC with KRAS, NRAS and BRAF mutations, who underwent 73 chemoembolization procedures with microspheres loaded with 100 mg of irinotecan, in combination with interspersed FOLFIRI chemotherapy. Response to treatment was assessed through computed tomography according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Assessment of adverse events utilized the Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE; version 5.0). Partial remission (PR) was observed in 11 (55%) patients while 5 (25%) patients showed stable disease (SD). Progression (PD) was observed in 4 (20%) patients. Median PFS was 9.1 months (95% CI: 7.2-10.1 months) and median OS was 20.7 months (95% CI: 18.2-23.3 months). The most common adverse events (AEs) resulting in treatment delay were hematological disorders, notably neutropenia (CTCAE grades 1-3). No deaths or AEs above grade 3 occurred during TACE. Continued FOLFIRI chemotherapy after TACE treatments resulted in grade 4 neutropenia in two patients, grade 3 in four patients and grade 2 thrombocytopenia in two patients. Combining FOLFIRI chemotherapy with chemoembolization procedures for liver metastatic lesions from colorectal cancer may provide a valuable treatment option for patients not qualified for monoclonal antibody therapy.

High-intensity focused ultrasound ablation combined with systemic therapy for unresectable colorectal cancer liver metastasis: A propensity score-matched analysis.

Unresectable colorectal cancer liver metastasis (CRLM) remains a challenging obstacle that often prevents curative treatment. In this study, we retrospectively analyzed the efficacy and safety of high-intensity focused ultrasound (HIFU) as a local adjuvant therapy for systemic chemotherapy for patients with unresectable CRLM. HIFU is a noninvasive method previously demonstrated as efficacious for various solid malignancies. Propensity score matching was used for the combination therapy group (HIFU group, n = 59) and the observation group receiving systemic therapy only (No-HIFU group, n = 59). In addition, the survival benefit, adverse effects, and factors affecting prognosis following HIFU were evaluated. The disease control rate was 77.9% and 62.7%, and the objective remission rate was 18.9% and 6.8% in the HIFU and non-HIFU groups, respectively. The survival analysis showed that median progression-free survival (mPFS) was 12.0 months and 11.0 months for the HIFU and non-HIFU groups, respectively (p = 0.002). The univariate and multivariate analysis showed that pre-treatment colorectal cancer liver metastasis lesion size was significantly associated with mPFS. In addition, patients that received a combination treatment for CRLM lesions <5.0 cm had a longer mPFS when compared to those receiving systemic therapy alone (13.0 months vs. 11.0 months, p = 0.001). In the HIFU group, patients with lesions <5.0 cm had a longer mPFS than patients with lesions ≥5.0 cm (13.0 months vs. 10.0 months, p = 0.04) (Figure3B,C). Most treatment-related adverse events observed in both groups were grade 1-2. Only four cases (6.8%) of grade 1-2 skin burns were observed in patients in the HIFU group; no other statistically significant adverse events were observed. Our study showed that HIFU ablation targeting unresectable CRLM alongside systemic therapy safely and significantly improved local control rates and prolonged mPFS, especially for lesions smaller than 5.0 cm.

103P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A

103P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A

150P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

150P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C

1628P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

1628P Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Impact of Surgical Management for Relapse After Conversion Hepatectomy for Initially Unresectable Colorectal Liver Metastasis: A Retrospective Cohort Study

BackgroundFor patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM. MethodsIn the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses. ResultsThe 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly. ConclusionFor IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.

Prognostic Value of TACE With Irinotecan-loaded Drug-eluting Beads (DEBIRI) in Patients With Liver Metastases from Unresectable Colorectal Cancer.

The standard of care for patients with colorectal cancer and liver metastases, who fail to respond to systemic chemotherapy has not yet been established. Therefore, we investigated the prognostic value of transarterial chemoembolization (TACE) using irinotecan-loaded drug-eluting beads (DEBIRI) in treating liver metastases due to colorectal cancer. Forty-six patients with colorectal cancer and unresectable liver metastases, who received systemic chemotherapy beyond the third line at our hospital between July 2014 and April 2020 were analyzed. They were divided into two groups: 1) Seventeen patients who received TACE with DEBIRI, and 2) twenty-nine patients who did not receive TACE. The median age was 68 years (range=37-85 years), and the male-to-female ratio was 29:17. The primary sites were the cecum in six cases, ascending colon in seven cases, transverse colon in two cases, descending colon in three cases, sigmoid colon in 14 cases, and rectum in 14 cases. All patients had received at least two prior systemic chemotherapy regimens including oxaliplatin-based and irinotecan-based regimens, and trifluridine tipiracil hydrochloride (38 patients) or regorafenib (12 patients) as the third line or beyond (overlap). Median survival was 272 days overall, 416 days in the TACE group, and 229 days in the non-TACE group, with significantly better survival in the TACE group (p=0.0126). TACE with DEBIRI may improve the prognosis of patients with liver metastases from unresectable colorectal cancer. We suggest that TACE with DEBIRI should be highly considered, especially in patients in whom liver metastasis may be a prognostic factor.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day.With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

P-104 Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

P-104 Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Preliminary results from a multi-cohort, multi-center phase II trial (ALTER-G-001)

Anlotinib plus chemotherapy as first-line therapy for patients with gastrointestinal tumor with unresectable liver metastasis: Results from a multi-cohort, multicenter phase II trial (ALTER-G-001).

e16268 Background: Patients (pts) with advanced gastrointestinal (GI) tumors, such as colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) or pancreatic cancer (PC), often developed liver metastases (LMs) with poor prognosis. Currently, there was no formal option for those, thus, more effective regimens were needed. Previously clinical trials had demonstrated anlotinib plus chemotherapy as first-line regimen had encouraging efficacy and safety in advanced CRC and ESCC, especially in pts with LMs. Therefore, we conducted a phase II trial evaluate efficacy and safety of anlotinib plus chemotherapy as first-line treatment in pts with unresectable LMs GI tumors. Methods: A total of 116 eligible pts with unresectable LMs gastrointestinal tumors and without previous systemic treatment would be divided into cohort A (mCRC), cohort B (ESCC) and cohort C (others, such as PC, GC, etc.,). All enrolled patients received 6 cycles (3 weeks per cycle) of induction therapy, cohort A receiving anlotinib (12mg, po, qd, d1-d14), oxaliplatin (130 mg/m2, iv, d1) and capecitabine (850 mg/m2, po, bid, d1-d14), cohort B receiving anlotinib, cisplatin (60-750 mg/m2, i.v., d1/d1-3) and paclitaxel (135 mg/m2, i.v., d1) or docetaxel (75 mg/m2, i.v., d1) and cohort C receiving anlotinib plus standard chemotherapy. Then, pts in all cohorts without PD and radical resection received anlotinib and metronomic capecitabine (500mg, po. bid, d1-21, q3w) until PD or unacceptable toxicity. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, PFS, OS, DCR, radical resection rate for LMs and safety. Results: As of February 8th, 2023, 55 pts were enrolled, 23 in cohort A, 2 in cohort B and 30 in cohort C (including 18 PC, 6 GC, 5 biliary tract cancer (BTC) and others), with a median age of 62.5 years old (range 34-74), 67.3% of male, 89.1% of ECOG PS 1. 70.9% of pts had LMs only. After induction therapy, 7 pts (5 CRC, 1 PC, 1 BTC) received surgical resection. In 24 evaluable pts in cohort C, 12 had partial response (PR), 9 had stable disease (SD). ORR was 50.0% and DCR was 87.5%. Among 13 evaluable pts with PC, 7 had PR, 5 had SD, with an ORR of 53.8%. In 15 evaluable pts in cohort A, 11 reached PR and 4 had SD. The ORR of cohort A was 73.3% and DCR was 100.0%. For one evaluable ESCC pts in cohort B, the best response was PR. The median PFS was not reached. 50.9% of pts had treatment emergent adverse events (TEAEs). Incidence of grade 3/4 TEAEs was 16.4%, mainly included white blood cell decreased (7.3%), neutropenia and hypertension (5.5%). Conclusions: Anlotinib plus chemotherapy showed significant efficacy and manageable toxicities as first-line treatment in advanced gastrointestinal tumors with LMs, especially in pancreatic cancer, which might provide a new treatment strategy for those. Clinical trial information: NCT05262335 .

Invited Commentary: Living-Donor Liver Transplantation for Patients with Unresectable Colorectal Cancer Liver Metastasis: New Option for Highly Selected Patients.

Journal of the American College of Surgeons ():10.1097/XCS.0000000000000728, May 09, 2023. | DOI: 10.1097/XCS.0000000000000728

Toronto Management of Initially Unresectable Liver Metastases from Colorectal Cancer in a Living Donor Liver Transplant Program.

Living donor liver transplantation (LDLT) is an attractive option for patients with unresectable, bilobar colorectal liver metastases (CRLM). However, it is not available in most centres beyond study protocols. This study describes the interim experience with LDLT for CRLM at a large North American transplant and hepatobiliary centre. Adults with unresectable CRLM, receiving systemic chemotherapy were recruited into a prospective clinical trial. Data on demographics, referral patterns, and clinical characteristics were extracted from October 2016 to February 2023. Patients were divided into three groups: transplanted, resected, and control (excluded, with continuation of systemic chemotherapy). Overall survival (OS) and recurrence-free survival (RFS) were compared. 81 referred patients were assessed for LDLT. 7 received transplants, 22 underwent resection, and 48 control. All had similar pre-assessment baseline characteristics. Median time from initial assessment to transplantation was 15.4 months. The control population had significantly worse post-assessment OS than the transplanted population (p=0.002) and resected population (p<0.001). The median post-operative follow-up duration was 21.4 months (resection) and 14.8 months (LDLT). There was no difference in OS between the transplanted and resected populations (1-year 100% vs. 93.8%; 3-year 100% vs. 43.3%, p=0.17). However, RFS was superior in the LDLT group (1-year 85.7% vs. 11.4%; 3-year 68.6% vs. 11.4%, p=0.012). Most patients with unresectable CRLM referred for LDLT are deemed ineligible for trial inclusion. However, the excellent oncologic outcomes in patients who meet criteria for LDLT supports its role in highly selected populations. Future results after the trial's completion will inform long-term outcomes.

Surgical Management of the Primary Tumor in Stage IV Small Intestinal Neuroendocrine Tumors: To Operate or Not to Operate, That Is the Question

Small intestinal neuroendocrine tumors (SI-NET) are rare tumors, often with distant metastases at diagnosis. The objective of this review is to provide an overview of the latest literature regarding surgical management of the primary tumor in stage IV SI-NET. Primary tumor resection (PTR) seems to be associated with improved survival in patients with stage IV SI-NET, independent of treatment of distant metastases. A watch and wait approach of the primary tumor increases the risk of needing an emergency resection. PTR improves survival in patients with stage IV SI-NET, decreases the risk of emergency surgery, and should be considered in all patients with stage IV disease and unresectable liver metastasis.

Outcomes of Patients With Colorectal Liver Metastasis in the Developing World: Is Liver Transplantation for Unresectable Liver Metastasis, the Next Logical Step?

While half of the patients with colorectal cancer develop metastasis, some 20% develop liver-only disease, and 10% of patients with unresectable liver disease live for 5 years. This study audits the outcomes of patients with colorectal liver metastasis to identify patients with unresectable liver metastasis eligible for a liver transplant. All patients with colorectal liver metastasis, irrespective of the presence of metastasis at other sites, registered between January 1, 2018, and December 31, 2019, were included in this retrospective audit. Patients in whom R0 Resection with adequate future liver remnant was not possible even after downstaging with chemotherapy were deemed unresectable. Overall survival was calculated using the Kaplan-Meier analysis. Patients eligible for a liver transplant were identified using the International Hepato-Pancreatico-Biliary Association (IHBPA) consensus guidelines and Oslo and Fong clinical risk scores. Out of 284 patients, 80 were treated with curative intent and 185 with palliative intent. At a median follow-up of 36 months, the median and 3-year OS were 37 months and 55% for the curative intent group and 9 months and 4% for the palliative intent group, respectively. Among 173 patients with liver-only metastasis, 13 patients (7%) satisfied the IHBPA consensus guidelines and had both Oslo and Fong scores of 2 or less. Transplant-eligible patients with unresectable liver metastasis had median and 3-year OS of 24 months and 25% against 9 months and 5% for ineligible patients, respectively. Liver transplant has the potential to benefit a small but significant portion of patients with unresectable liver metastasis.