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

BACKGROUND/AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Interventional radiological therapies in colorectal hepatic metastases.

Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.

Case report and literature review: PET/CT in the evaluation of response to treatment of liver metastasis from colorectal cancer with DEBIRI-TACE.

Background: Irinotecan-loaded drug-eluting beads transarterial chemoembolization (DEBIRI-TACE) is a safe and effective therapeutic option for unresectable colorectal liver metastases (CRLM). The evaluation of treatment response after DEBIRI-TACE is very important for assessing the patient's condition. At present, the Response Evaluation Criteria in Solid Tumors (RECIST) with the tumor size obtained by CT and/or MRI and PET Response Criteria in Solid Tumors (PERCIST) based on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) are used for evaluating the response to therapy of solid tumors; however, their value in the assessment of treatment response after DEBIRI-TACE remains unclear. Case presentation: A 52-year-old male with unresectable simultaneous CRLM was treated in the Affiliated Hospital of Yanbian University with DEBIRI-TACE combined with systemic chemotherapy and targeted therapy. Carcinoembryonic antigen levels decreased by 82.50% after 27 days of treatment. At 6 weeks post-surgery, FDG-PET/CT showed that the maximum standardized uptake value (SUVmax) of intrahepatic lesions was reduced to 62.14%. Abdominal MRI revealed that the sum of target lesion diameters was less than 30% that at baseline. PERCIST indicated partial metabolic response, whereas RECIST suggested stable disease. Conclusion: FDG PET/CT-based PERCIST may be accurate in determining treatment response and evaluating patient prognosis after DEBIRI-TACE in unresectable CRLM.

Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy for Refractory Colorectal Liver Metastasis: A Systematic Review.

Colorectal cancer and related mortality present a profound challenge in its management, even in this modern age. Even today, colorectal cancer-related deaths rank third in the world. Despite having multiple lines of chemotherapy, combined with radiotherapy and chemoembolization techniques, after or before surgical resection, the five-year survival rate is approximately 20%. Drug-eluting bead, irinotecan (DEBIRI) is a new technique that involves embolization of the feeding vessels to the tumour and delivering irinotecan for its chemotherapeutic effects. A significant amount of literature compares DEBIRI as an adjunct to various lines of chemotherapy. However, so far, not much data are available on DEBIRI as a singular treatment for those patients who have had multiple chemotherapies and still progressing and are not fit for liver resection. In this systematic review, we aim to highlight and bring together the results of those studies that focused on this specific patient group. A systematic search of the literature involving three large databases (published between January 2017 and July 2022), excluding languages other than English, was conducted to identify articles documenting patients who had disease progression despite chemotherapy and were not fit for surgical resection. The level of evidence and the quality check were assessed by two independent reviewers, and consensus with the senior author resolved disagreements. Out of seven studies that met the final criteria, we found a pooled cohort of 302 patients. The mean age of the patients was 61.2 years, ranging from 40.7 to 84 years. The most commonly used DEBIRI beads were M1 (70-150 um) and M2 (100-300 um), but two studies reported the use of 40 um as well. The total number of DEBIRI treatments performed in our pooled cohort was 904. The majority of the studies reported only G1/G2 toxicities among the patients, with maximal toxicity of G4 in a few selected patients. The median overall survival in our pooled cohort was 19.52 months. The median progression-free survival in our data was 5.76 months. Our systematic review concludes that DEBIRI is undoubtedly a useful treatment modality with an acceptable toxicity profile. This treatment offers a good overall survival benefit for refractory colorectal liver metastasis.

Safety, Feasibility and Technical Considerations from a Prospective, Observational Study-CIREL: Irinotecan-TACE for CRLM in 152 Patients.

CIREL, a prospective, Europe-wide, observational study aimed to assess the real-world feasibility and tolerability of irinotecan-based transarterial chemoembolization (LP-irinotecan TACE) for unresectable colorectal cancer liver metastases with regard to the treatment plan and adverse events (AEs). CIREL enrolled 152 eligible patients (≥18 years) with liver-only or dominant metastases treated with LP-irinotecan TACE following a multidisciplinary tumor board decision. Data were prospectively collected for baseline, the number of planned and performed sessions, and technical information and safety according to CTCAE 4.03/5.0. Results from 351 analyzed treatment sessions showed technical success for 99% of sessions, and 121 patients (79%) completed all planned sessions. Further, 60% of sessions were performed using opioids, 4% intra-arterial anesthetics, and 25% both. Additionally, 60% of patients experienced at least one peri-interventional AE of any grade; 8% of grade 3−4. Occurrence of AEs was related to larger liver-involvement (p < 0.001), bi-lobar disease (p = 0.002), and larger beads (p < 0.001). Using corticosteroids together with antiemetics showed reduced and lower grade vomiting (p = 0.01). LP-irinotecan TACE was tolerated well and had a high proportion of completed treatment plans. This minimally invasive locoregional treatment can be used together with concomitant systemic therapy or ablation.

The Role of Conventional TACE (cTACE) and DEBIRI-TACE in Colorectal Cancer Liver Metastases.

Colorectal cancer (CRC) is one of the most common tumor entities worldwide and a common cause of cancer-associated death. Colorectal cancer liver metastases (CRLM) thereby constitute a severe life-limiting factor. The therapy of CRLM presents a major challenge and surgical resection as well as systemic chemotherapy remain the first-line treatment options. Over the years several locoregional, vascular- and image-based treatments offered by interventional radiologists have emerged when conventional therapies fail, or metastases recurrence occurs. Among such options is the conventional/traditional transarterial chemoembolization (cTACE) by local injection of a combination of chemotherapeutic- and embolic-agents. A similar treatment is the more recent irinotecan-loaded drug-eluting beads TACE (DEBIRI-TACE), which are administered using the same approach. Numerous studies have shown that these different types of chemoembolization can be applied in different clinical settings safely. Furthermore, such treatments can also be combined with other local or systemic therapies. Unfortunately, due to the incoherent patient populations of studies investigating TACE in CRLM, critics state that the definite evidence supporting positive patient outcomes is still lacking. In the following article we review studies on conventional and DEBIRI-TACE. Although highly dependent on the clinical setting, prior therapies and generally the study population, cTACE and DEBIRI-TACE show comparable results. We present the most representative studies on the different chemoembolization procedures and compare the results. Although there is compelling evidence for both approaches, further studies are necessary to determine which patients profit most from these therapies. In conclusion, we determine TACE to be a viable option in CRLM in different clinical settings. Nevertheless, a multidisciplinary approach is desired to offer patients the best possible care.

Local Treatments in the Unresectable Patient with Colorectal Cancer Metastasis: A Review from the Point of View of the Medical Oncologist.

For patients with isolated liver metastases from colorectal cancer who are not candidates for potentially curative resections, non-surgical local treatments may be useful. Non-surgical local treatments are classified according to how the treatment is administered. Local treatments are applied directly on hepatic parenchyma, such as radiofrequency, microwave hyperthermia and cryotherapy. Locoregional therapies are delivered through the hepatic artery, such as chemoinfusion, chemoembolization or selective internal radiation with Yttrium 90 radioembolization. The purpose of this review is to describe the different interventional therapies that are available for these patients in routine clinical practice, the most important clinical trials that have tried to demonstrate the effectiveness of each therapy and recommendations from principal medical oncologic societies.

Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit Preclinical Model.

PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70-150 µm, DC Bead LUMI™, Biocompatibles UK Ltd-Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post-TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076-0.105 mL) and 1.99 mg/kg (1.51-2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within 2 weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m2) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Updates of colorectal cancer liver metastases therapy: review on DEBIRI.

Colorectal cancer is a worldwide public health issue, presenting an advanced stage at diagnosis in more than 20% of patients. Liver metastases are the most common metastatic sites and are not indicated for resection in 80% of cases. Unresectable colorectal cancer liver metastases that are refractory to systemic chemotherapy may benefit from transarterial chembolization with irinotecan-loaded beads (DEBIRI). Several studies show the safety and efficacy of DEBIRI for the treatment of colorectal cancer liver metastases. The development of transarterial chembolization and the introduction of new embolics have contributed to better outcomes of DEBIRI. This article reviews the current literature on DEBIRI reporting its use, efficacy in terms of tumor response and survival and side effects.

Transarterial Chemoembolisation of Colorectal Liver Metastases with Irinotecan-Loaded Beads: A Bi-institutional Analysis of 125 Treatments in 53 Patients.

PURPOSE: To retrospectively review outcomes in patients treated for colorectal liver metastases with DEBIRI. MATERIALS AND METHODS: A retrospective analysis of patients with CRLM treated with DEBIRI was performed between 2008 and 2017 between two tertiary centres. Outcome parameters were overall survival and hepatic progression-free survival, as well as safety. Subgroup analyses were performed to assess the impact on outcomes of hepatic tumour burden at time of treatment, the presence of extrahepatic disease, prior systemic chemotherapy and the prior administration of systemic irinotecan-containing chemotherapy. RESULTS: Fifty-three patients received 125 treatments with DEBIRI over the study period. Median age of patients was 71 (range 41-88). Patients previously received a median of 1 line of chemotherapy (range 1-5). Median number of DEBIRI treatments was 2 (range 1-6). The median survival from first treatment was 14.5 months (range 1-107). Median hepatic progression-free survival was 5 months (0-86.5 months). The presence of extrahepatic disease (seen in 45% of patients) correlated with lower OS. Prolonged OS was seen in patients who received previous ablation and systemic chemotherapy. Technical success rate was found to be 99%. Post-procedural complication rate was 6%. CONCLUSION: Our findings add to the growing body of literature to support the safety profile of DEBIRI in the treatment of CRLM. Further studies will be necessary to help establish the optimum berth of DEBIRI in the treatment algorithm for colorectal liver metastases.

Toward a better understanding of the mechanism of action for intra-arterial delivery of irinotecan from DC Bead(TM) (DEBIRI).

DC Bead is designed for the embolization of liver malignancies combined with local sustained chemotherapy delivery. It was first demonstrated around a decade ago that irinotecan could be loaded into DC Bead and used in a transarterially directed procedure to treat colorectal liver metastases, commonly referred to as drug-eluting bead with irinotecan (DEBIRI). Despite numerous reports of its safe and effective use in treating colorectal liver metastases patients, there remains a perceived fundamental paradox as to how this treatment works. This review of the mechanism of action of DEBIRI provides a rationale for why intra-arterial delivery of this prodrug from an embolic bead provides for enhanced tumor selectivity, sparing the normal liver while reducing adverse side effects associated with the irinotecan therapy.

Chemoembolization with CalliSpheres drug-eluting beads loaded with irinotecan in the treatment of unresectable colorectal cancer liver metastases: preliminary results in 16 cases.

BACKGROUND: To analyze the perioperative safety and effectiveness of chemoembolization with CalliSpheres drug-eluting beads (DEBs) loaded with irinotecan (DEBIRI) in the treatment of unresectable colorectal cancer liver metastases (CRCLM). METHODS: The clinical data of 16 colorectal cancer patients with postoperative liver metastases who were treated with chemoembolization using DEBIRI in our center from March 2017 to December 2018 were retrospectively analyzed. The treatment responses 3 and 6 months after the chemoembolization was evaluated with the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The clinical complications were recorded and graded. Changes in blood cells, liver function, and tumor marker were analyzed before treatment and during follow-up. RESULTS: A total of 46 DEBIRI sessions were performed in 16 patients. The success rate was 100.0%. The main postoperative complications included right upper quadrant pain (76.1%), hypertension (87.0%), nausea (89.1%), and vomiting (84.8%), which were grade 1 to 2 events; one patient suffered from acute cholecystitis (2.2%), a grade 3 event. According to mRECIST, the complete response rate, partial response rate, objective response rate, and disease control rate were 0.0%, 68.7%, 68.7%, and 100.0% 3 months after chemoembolization and 0.0%, 81.2%, 81.2%, and 93.7% 6 months after the intervention. As shown by blood biochemistry, the carcinoembryonic antigen (CEA) significantly differed before treatment and during follow-up (P<0.01), while blood cells and liver function showed no significant differences (all P>0.05). CONCLUSIONS: In this preliminary clinical study, chemoembolization with DEBIRI is safe and effective in treating unresectable CRCLM. However, more prospective multicenter clinical trials with larger sample sizes are required to confirm our findings further.

DEBIRI plus capecitabine: a treatment option for refractory liver-dominant metastases from colorectal cancer.

Aim: This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases. Patients & methods: Forty patients with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m2 twice-daily on days 1-14 every 3 weeks. Results: Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients. Conclusion: DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.

Decision Making in Interventional Oncology: Intra-arterial Therapies for Metastatic Colorectal Cancer-Y90 and Chemoembolization.

Colorectal cancer is the third most common cancer in the United States and the liver is the most common site of metastatic disease. The presence and extent of hepatic metastases are a major prognostic indicator. Although surgical resection is the accepted first-line therapy for colorectal liver metastasis, only 20 to 25% of patients are eligible for resection due to the extent and location of disease. This article discusses the current role of transarterial therapies in the treatment of colorectal liver metastases.

Third-line treatment of colorectal liver metastases using DEBIRI chemoembolization.

To evaluate safety, efficacy of drug-eluting beads with irinotecan (DEBIRI) on local response and survival of patients affected by colorectal liver metastases (CRLM) progressing during or after second line was evaluated. Sixty-two patients, with colorectal liver metastases, not suitable for surgery or thermal ablation treatments, progressing during or within 6 month from the end of second-line chemotherapy, were treated with DEBIRI chemoembolization between February 2009 and July 2014. CRLM were histologically confirmed. Exclusion criteria were considered. The DEBIRI technique consists in intrahepatic embolization of metastases with non-absorbable beads (75-150 µm and 100-300 µm) preloaded with irinotecan, carried near tumour using a selective catheterization of the right or of the left hepatic artery. To control pain associated with treatment, we use a specific schedule. Efficacy of treatment, defined as lack of disease progression and reduction in size of metastasis according to RECIST 1.1 criteria, was evaluated after two treatments with contrast-enhanced computed tomography (CT) at 4 months. If necessary, more treatments are repeated. A total of 191 procedures were performed. No intra-/peri-procedural death occurred. Pain and post-embolization syndrome were generally controlled by medications. Overall, the efficacy of treatment, evaluated in terms of stability and remission of the disease, was 37.1%. In our experience, DEBIRI technique results as a safe and effective procedure, with good intra- and peri-procedural tolerability.

A pilot study employing hepatic intra-arterial irinotecan injection of drug-eluting beads as salvage therapy in liver metastatic colorectal cancer patients without extrahepatic involvement: the first southern Italy experience.

BACKGROUND: The main aim of this prospective study was to evaluate the efficacy of drug-eluting beads with irinotecan (DEBIRI) for liver metastases from colorectal cancer. Secondary aims were to evaluate survival and toxicity. METHODS: Twenty-five patients with metastases in <50% of the liver and without extrahepatic involvement were enrolled. Treatment response assessment was performed by multidetector contrast enhancement computed tomography (MDCT) with evaluation of the enhancement pattern of the target lesion and tumor response rates according to modified Response Evaluation Criteria in Solid Tumors (mRECIST, Version 1.1). All adverse events were recorded by the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events, Version 3.0. Associations of tumor response and variables were calculated using the chi-squared test. Overall survival (OS) was calculated using the Kaplan-Meier method. Comparisons were made using the log-rank test. RESULTS: According to mRECIST, complete response (CR) was observed in 21.8% of patients, partial response (PR) in 13%, stable disease (SD) in 52.2% and progressive disease (PD) in 13% of patients. Response rate (RR = CR + PR) was 34.8%. No associations between treatment response and variables such as Dukes' classification, grading and Kras status were found (P>0.05). The median OS was 37 months (95% CI: 13.881 to 60.119). Cox regression model showed that neither site, Dukes' classification, grading, Kras status nor number of chemotherapy treatments pre-DEBIRI influenced the OS. The log-rank test showed no statistically significant difference in OS among patients who underwent 1, 2 or 3 DEBIRI treatments (χ2=2.831, P=0.09). In our study, the main toxicities included postembolization syndrome (PES), hypertransaminasemia and fever. CONCLUSION: The favorable tumor response and the favorable toxicity profile make DEBIRI treatment a potential third-line therapy. Although further larger studies are needed to confirm these data, we can state that DEBIRI is an attractive emerging treatment in these patients.

PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer.

PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233).

A novel approach to inoperable or recurrent rectal cancer by chemoembolization: A new arrow in our quiver?

PURPOSE: Assess the feasibility, safety and efficacy of TACE with irinotecan loaded micro particles (debiri) for the treatment of locally advanced rectal cancer patients. RESULTS: We assessed the Edmonton Symptom Assessment System (ESAS). The tool is designed to assess nine common symptoms in cancer patients: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath. The ESAS score was 7 in 10/12 (83%) patients before treatment and 6 in 2/12 (16.5%) patients. After treatment in 6/12 (50%) patients the score dropped to 3; 3/12 (33%) reported 4, 1/12 (8%) reported 2. All patients experienced local control disease with a degree of citoreduction; in 4 cases (33%) we observed outstanding responses with a dramatic reduction in the tumors size which led us to surgical radical resections. MATERIALS AND METHODS: We run a prospective mono-institutional study where we recruited, 12 non- consecutive patients with histology confirmation of rectal cancer, inoperable and not treatable due to severe comorbidities, or pelvic recurrence/progression after curative treatment, chemotherapy, radiotherapy and/or surgery. Their performance status (PS) ECOG was 2-3 . Twelve patients (10 male and 2 female) with a median age 71 (range 56-89) were recruited in the study. CONCLUSIONS: The study has met the primary endpoint and showed encouraging activity. Debiri could be a possible option for locally advanced/inoperable or recurred rectal cancer patients. Further trials are warranted to validate this methodic in early stages.

Early Experience with 70-150 µm Irinotecan Drug-eluting Beads (M1-DEBIRI) for the Treatment of Unresectable Hepatic Colorectal Metastases.

AIM: To report our early experience on the feasibility and safety of 70-150 µm drug-eluting beads loaded with irinotecan (M1-DEBIRI) for treating unresectable hepatic colorectal metastases. PATIENTS AND METHODS: An Institutional Review Board-approved, prospectively maintained, multi-institutional registry was evaluated from 2/2009 to 8/2013. Fifteen consecutive patients presenting with liver-dominant metastatic colorectal cancer were treated with M1-DEBIRI. Kaplan-Meier statistics was used to evaluate hepatic progression-free-survival and overall survival. RESULTS: Fifteen patients underwent 32 DEBIRI treatments. The mean prescribed dose was 100 mg of irinotecan (range=100-200 mg). In 75% of treatments (n=24), 100% of the prescribed dose was delivered before complete stasis. In 97% of treatments (n=31), at least 50% (median 100 mg, range 25-150 mg) of the prescribed dose was delivered. There was grade 2 abdominal pain after one treatment (3%). In another patient, increased total bilirubin (1.1 to 3.1 mg/dl) was seen after one treatment. There was 42% reduction in median carcinoembryonic antigen level and 33% (5/15 patients) with Response Evaluation Criteria in Solid Tumors (RECIST) objective response (complete and partial). Modified RECIST and European Association for the study of the Liver (EASL) objective response rates were both 73% (11/15 patients). The disease control rate was 93% (14/15 patients). Hepatic progression-free-survival and overall survival were 8 and 13 months respectively. Disease in one patient was down-staged to resection (6%). CONCLUSION: M1-DEBIRI appears to be safe and feasible in the treatment of metastatic colorectal cancer. Smaller beads also provide efficient irinotecan dose delivery. Larger studies are needed to validate these findings.

Comparison of tumor response assessment methods in patients with metastatic colorectal cancer after locoregional therapy.

BACKGROUND: We evaluated the performance of the Response Evaluation Criteria in Solid Tumor (RECIST), modified RECIST, and the European Association for the Study of Liver (EASL) guidelines and correlated them with survival in patients with metastatic colorectal cancer (mCRC) treated with locoregional therapy (LRT). PATIENTS AND METHODS: Our LRT registry was evaluated from 2008 to 2013. 228 mCRC patients were treated with LRT (91% drug-eluting beads, 9% radioembolization) were evaluated. Cox regression and Kaplan-Meier (KM) statistics were utilized for survival analysis. RESULTS: Excellent inter-rater agreement between EASL/mRECIST (κ = 905) was seen. Correlations between RECIST/mRECIST (κ = 0.638) and EASL/RECIST were weaker (κ = 0.638 and 0.598, respectively). There were significant differences in KM and Cox regression survivals between responders and nonresponders with all three methods (all P < 0.0001). Multivariate analysis identified RECIST response, tumor extent, performance status, concomitant chemotherapy, and prior surgery/ablation as independent prognostic factors. EASL response and mRECIST response were not found to be independent prognostic factors. CONCLUSION: Imaging biomarkers are not efficient and do not represent ideal surrogates for survival; however, they all display prognostic significance. RECIST is superior to mRECIST/EASL given its ability to stratify survival benefit according to response category and demonstrate independent prognostic significance. J. Surg. Oncol. 2016;113:443-448. © 2016 Wiley Periodicals, Inc.