Management Of Liver Metastases Research Articles

Hepatectomy for liver metastases from gastric cancer: a systematic review

BackgroundOfficial guidelines recommend palliative treatments for patients with liver metastases from gastric cancer. However, many case series reported that hepatectomy for such cases is safe and effective. This systematic review compares the overall survival between hepatectomy and palliative therapy in patients with liver metastases from gastric cancer.MethodsTwo independent reviewers performed a systematic search of literature in EMBASE and PubMed, updated until 26 October 2016. The Newcastle-Ottawa score for cohort studies was used for quality assessment of included studies.ResultsA total of eight cohort studies involving 196 patients in the hepatectomy arm and 481 in the palliative arm were included. Median overall survival of patients in the two arms was 23.7 (range, 13.0 to 48.0) and 7.6 (range, 5.5 to 15.2), respectively. Median rates of overall survival of the two arms were 69, 40, 33 and 27, 8, 4% at 1, 2, and 3 years, respectively. Comparing with palliative therapy, hepatectomy was associated with significantly lower mortality at 1 year (odds ratio 0.17, P < 0.001) and 2 years (odds ratio 0.15, P < 0.001). Among the patients who underwent hepatectomy, Asian cohorts showed higher median rates of overall survival than Western cohorts at 1 year (76 vs. 60%), 2 years (47 vs. 30%) and 3 years (39 vs. 23%).ConclusionsHepatectomy in the management of liver metastases from gastric cancer can be considered effective. In the elective setting, hepatectomy provides a potential alternative to palliative therapy.

Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20% according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (111In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

Management of liver metastases in colorectal cancer patients: A retrospective case-control study of systemic therapy versus liver resection

ObjectiveTo evaluate and compare the overall survival (OS) in case-matched patient groups treated either with systemic therapy or surgery for colorectal liver metastases (CRLM). MethodsPatients with CRLM, without extra-hepatic disease, treated with chemotherapy with or without targeted therapy in two phase III studies (n = 480) were selected and case-matched to patients who underwent liver resection (n = 632). Matching criteria were sex, age, established prognostic factors for survival (clinical risk score). Available computed tomography (CT)-scans of patients treated with systemic therapies were reviewed by three independent liver surgeons for resectability. Survival was compared between patients with resectable CRLM (based on CT-scan review) who were treated with systemic therapy versus patients who underwent liver resection. ResultsA total of 96 patients treated with systemic therapy were included. Pre-treatment CT-scans of the liver were available for review in 56 of the systemically treated patients, and metastases were unanimously considered resectable in 36 patients (64.3%) (complex resectable: n = 25; 69%). These 36 patients were case-matched with 36 patients who underwent liver resection (wedge resection or segmentectomy: n = 26; 72%). Median OS in the patient group treated with systemic therapy was 26.5 months (range 0–81 months), which was significantly lower than that in case-matched patients who underwent liver resection (median OS 56 months; range 6–116) (p = 0.027). ConclusionsIn this case-matched control study, surgery provided superior OS rates compared to systemic therapy for CRLM. Resection of CRLM should always be considered, preferably in a dedicated liver centre, since not all patients that qualify for resection are identified as such.

Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature

Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

A national survey on the management of liver metastases from colorectal cancer (CRC): Comparison of perspectives and expectations among medical oncologists and hepatobiliary surgeons across Canada.

690 Background: To compare the perspectives of medical oncologists versus hepatobiliary surgeons in the management of liver metastases from CRC. Methods: Medical oncologists and hepatobiliary surgeons across Canada were surveyed to evaluate for criteria used to determine resectability of liver metastases from CRC and availability of multidisciplinary clinics. Results: Of 220 experts surveyed, 145 (66%) responded. 137 (95%) had received specialized training in oncology. Only 37 (26%) respondents reported access to both multi-disciplinary tumor boards and clinics. 109 (75%) reported lack of institutional criteria. Oncologists and surgeons disagreed with regard to absolute contraindications for resection of hepatic metastases. More oncologists reported a higher percentage of liver parenchyma involvement (70% vs. 45%), proximity to major vessels and poor performance status as contraindications compared to surgeons (p &lt; 0.05). All physicians deemed CT as the preferred first-line imaging study for evaluating CRC liver metastases with significantly more surgeons indicating the need for MRI of the liver (p &lt; 0.05). Oncologists and surgeons also showed high discordances with respect to both clinical and radiographic findings in terms of their influence on surgical decision regarding resection of liver metastases (Table). Conclusions: Medical Oncologists and surgeons have discordant criteria with respect to resection of hepatic metastases and the roles they play in the management of these complex patients. Uncertainties and discordances can lead to deficiencies in care, supporting the need for a standardized clinical preoperative risk scoring system for resection of liver metastases from CRC. [Table: see text]

Colorectal Liver Metastases: A Never Ending Story.

See Article on Page 92-100 To improve the quality of life and outcomes for patients with colorectal liver metastases, we would like to emphasize some points. First, a colorectal multidisciplinary teams (MDT) should also include a specialized hepatobiliary MDT that has the expertise and the facilities to provide surgery for patients with liver metastases. The cases of patients being considered for treatment of hepatic metastases should be discussed at a multidisciplinary meeting in which the participants have experience in the management of liver metastases [1]. Second, traditional risk factors, as well as the indications and the contraindications, for a hepatic resection should be abandoned. The present principle as to resectability is that resection should be performed if all metastases, regardless of their sizes, number, locations and distribution, can be removed while leaving a sufficient remaining liver parenchyma [2]. As is known, the number of liver metastases, the spread of colorectal cancer to the lymph nodes, the maximum size of the metastases, the preoperative carcinoembryonic antigen level, the extrahepatic spread, and the use of a nonradical resection represent independent risk factors for recurrence [3,4]. Third, All resources should be used. Perioperative chemotherapy, portal vein embolization, a 2-stage hepatectomy, and local ablative therapies might improve outcomes.

Current status of hepatic resection for patients with colorectal liver metastasis

Liver metastasis is responsible for the majority of death of patients with colorectal cancer. The hepatic resection is curative standard treatment of colorectal liver metastasis. More and more patients with liver metastases from colorectal cancer were indicated to be resected because of progress in both surgical technique and systemic therapies. As a result, many surgeons take a more aggressive attitude towards the management of liver metastasis. In addition, multidisciplinary team of colorectal liver metastasis has helped to standardize clinical practice of synchronous and metachronous liver metastases.

The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments.

The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival. The study involved 122 patients (77 males), aged 64.0 ± 11.0 years (range: 27.8-86.1) at diagnosis of liver metastatization (synchronous in 59). All underwent chemotherapy and at least one procedure of radiofrequency ablation; 53 also had partial hepatic resections. Demographics, tumor characteristics and survival outcomes from liver metastatization were analyzed with univariate and multivariate techniques. This analysis was performed also taking into account relative survival as the best estimate of specific survival. The analysis with observed survival selected the categorized number of involved lymph nodes in the colorectal specimens as the only statistically significant predictor, while the analysis with relative survival also showed site of the primary tumor (above the sigmoid colon or otherwise) and number of liver metastases as significant factors. The standardized mortality ratio was 9.673 (95% CI: 7.668-11.663) and a total of 201.85 years of life were lost in comparison with the survival of the reference population. The computation of relative survival – better than observed survival – selected a more adequate number of predictors, making investigation of even limited series of patients with confounding factors reliable. The finding that prognosis was mainly dependent on the anatomical presentation of the primary tumor and of liver metastases – instead of treatments – could explain the still contrasting opinions on the role of the available therapies in this field.

PTH-330 Detection and treatment of liver metastasis from colorectal cancer

Introduction As the principal site of distant spread, the detection and management of liver metastasis is crucial in patients with colorectal cancer. Untreated, the median survival is around 6–12 months. The aim of this study was to assess the way in which colorectal liver secondaries are detected and to assess the outcomes associated with their management. Method We set up and prospectively maintained a database detailing the clinical and radiological features of all patients with liver metastasis secondary to colorectal cancer in a high-volume unit. For the period 2008–2012, we reviewed the events leading to a diagnosis of liver metastasis, the initial treatment intent and median survival rates. Results During the study period, 1292 new cases of colorectal cancer were discussed in our multidisciplinary team meeting and of these, 216 had liver metastasis confirmed by computed tomography (CT) scanning. Liver metastasis was noted at the time of the initial diagnosis in 160 patients and metachronous lesions were detected in 56 patients. Metachronous metastases were detected after a median of 12 months (range 3–53). The length of the interval had no bearing on survival. The majority of metachronous liver metastases were detected with scheduled monitoring (41% by carcino-embryonic antigen and 39% on surveillance CT scan) but 16% presented symptomatically. From the time of initial diagnosis, the median survival for the synchronous and metachronous cases was 53 months and 57 months, respectively. 20% of the synchronous and 88% of the metachronous cases were treated with curative intent after the initial diagnosis of colorectal cancer. Of the 216 patients diagnosed with liver metastasis, 50 (23%) were referred to the local hepatobiliary unit for consideration of metastectomy. 11 patients were deemed unresectable and a further eight patients were either unfit or declined resection. Liver resection was undertaken in 9% of the synchronous and 30% of the metachronous cases. From the time of their initial diagnosis, the median survival for the 31 patients who underwent hepatic metastectomy was 53 months; survival was 59 months in the synchronous and 47 months in the metachronous groups. Conclusion Scheduled colorectal cancer surveillance serves to identify the majority of liver metastases, but history-taking and examination lead on to detection in a significant minority. With appropriate patient selection, resection of both synchronous and metachronous liver secondaries offers a significant survival benefit. Disclosure of interest None Declared.

肝切除後3年無再発生存中の膵癌肝転移の1例

症例は68歳，女性．膵体部癌に対し膵体尾部切除術・D2郭清を施行し，半年間，術後補助化学療法（gemcitabine）を行った．術後1年2カ月に肝S6単発の肝転移再発と診断した．S-1投与により，1年1カ月の間，stable diseaseを維持した肝転移巣が，腫瘍径増大による，progressive diseaseとなった．全身状態は良好で，他の化学療法の選択肢がないこと，他の肝転移巣および遠隔転移巣を認めないことから肝S6部分切除術を施行した．肝転移術後3年1カ月（原発巣術後5年5カ月，肝転移診断後4年3カ月）無再発生存中である．切除を治療のオプションに加えることにより，長期生存を得ている膵癌肝転移の1例を報告する．

Abstract 2094: Regulation of site-specific liver metastasis by collagen IV-conveyed signals

Abstract The liver is a primary site of metastasis for some of the most common human malignancies. At present, surgical resection is the most effective curative option for liver metastases, but most patients with liver metastases still succumb to their disease. A better understanding of the underlying biology is essential for design of more effective therapy. We previously identified basement membrane type IV collagen α1/α2 expression levels as determinants of the liver colonizing potential in a murine lung carcinoma model (1) and observed high collagen IV expression levels in surgical specimens of liver metastases from diverse tumor types. The aim of this study was to elucidate the functional relevance of increased collagen IV expression to liver metastases formation. We reported that collagen IV α1/α2 overexpression in non-metastatic lung carcinoma M-27 (M27colIV) cells increased specifically their liver (but not lung) metastasizing potential. A transcriptome analysis was therefore performed on these cells in order to identify changes to gene expression that could account for the newly acquired metastatic potential. This analysis revealed that type IV collagen levels regulated the expression of multiple genes. Prominent among them were genes encoding for chemokines such as CCL-5 and CCL-7 and for growth factors such as amphiregulin (AREG) that were all upregulated by ≥ 3 fold. These changes were validated at the RNA and protein levels using qPCR and Western blotting, respectively. When the expression of these genes in M27colIV cells was subsequently silenced using shRNA, a significant decrease (5-10 folds) was observed in their ability to generate experimental liver metastases, as compared to wild type or mock-transfected cells and they failed to develop metastases in 40-50 % of injected mice. A similar correlation between CCL-5 and CCL-7 expression levels and liver metastases formation was also noted in human colon carcinoma cell lines. The results identify a type IV collagen-regulated gene expression signature that promotes liver metastasis and suggest that collagen IV-induced changes in chemokine and growth factor production levels mediate this effect. They provide a rationale for further exploration of the clinical utility of CCL-5, CCL-7 and AREG as targets in the management of liver metastases. Supported by a grant from the Canadian Institute for Health Research (to PB) and a Henry R. Shibata Cedars Cancer Fellowship (to RR). REFERENCES 1. Burnier JV, Wang N, Michel RP, Hassanain M, Li S, Lu Y, et al. Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis. Oncogene. 2011;30:3766-83. Citation Format: Roni F. Rayes, Ni Wang, Julia V. Burnier, France Bourdeau, Pnina Brodt. Regulation of site-specific liver metastasis by collagen IV-conveyed signals. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2094. doi:10.1158/1538-7445.AM2014-2094

Role of surgery in the treatment of liver metastases from gastric cancer

The development of liver metastases is a fatal event for gastric cancer patients, and remains a major cause of cancer-related death. Many studies showed that the 5-year survival rate is as low as about 10% in these cases. The management of liver metastases from gastric adenocarcinoma remains controversial. The different therapeutic modalities used are surgery, radiofrequency ablation, hepatic arterial infusion and palliative gastrectomy. Surgery is a good indication for single liver metastasis of gastric carcinoma less than 5 cm and not associated with another extra-hepatic metastasis. In this article we discuss the role of surgery in the treatment of liver metastases from gastric cancer.

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation

Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments. To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases. Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked. Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted. The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained. There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection. Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Successful treatment of liver metastasis from solid pseudopapillary tumor of the pancreas: a

Solid pseudopapillary tumor of the pancreas is a rare pancreatic neoplasm that typically occurs in young females. As a low-grade malignancy, the tumor seldom recurs and metastasizes. Management of liver metastasis from such a tumor remains unclear. We present a case of a young girl with liver metastasis due to solid pseudopapillary tumor of the pancreas. She was admitted with chief complaints of epigastric mass on palpation for 16 months and upper abdominal pain for 2 months. An abdominal CT scan detected a mass in the pancreas and multiple nodules in the liver. Then, percutaneous CT-guided tru-cut biopsy was performed and pathological diagnosis of the biopsy material revealed solid pseudopapillary tumor of the pancreas. At 3 months after surgical resection of the pancreatic and liver tumors, CT scan found nodules in her liver. The patient received treatment with transcatheter arterial chemoembolization. She remained well during the 3 years of follow-up with no evidence of recurrence. Therefore, it is suggested that although solid pseudopapillary tumor of the pancreas may be associated with malignant potentiality, a favorable prognosis can also be obtained via rigorous treatment.

Multidisciplinary Approach as the Key Factor in the Management of Liver Metastases from Colorectal Cancer

Multidisciplinary Approach as the Key Factor in the Management of Liver Metastases from Colorectal Cancer

InSIRT trial: Single-center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver-predominant metastatic colorectal adenocarcinoma after failure of first-line combination chemotherapy.

e14079 Background: Liver metastases develop in half of colorectal cancer (CRC) cases and once metastatic, ~90% die due to their consequences. We are evaluating the aggressive management of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using Yttrium-90 (Y-90) radioactive microspheres after evidence of progressive disease following 1st-line FOLFOX ± bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. Methods: Subjects with predominant hepatic metastatic CRC despite 1st-line FOLFOX based therapy ± bevacizumab are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives SIRT followed by 2nd-line FOLFIRI 4-6 weeks after the final SIRT. Results: To date, 9 metastatic CRC subjects have been treated and 10 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. 4 of 9 subjects (45%) achieved PFS at 6 mos and average TTP is 7 months(0.7-21.3 mos). Overall treatment has been well tolerated, except one possible study related SAE of liver failure. The OS endpoint has not been achieved. Conclusions: Historically, 2nd-line FOLFIRI has achieved a 2.5 mos median PFS. Our preliminary results of 9 subjects with metastatic CRC show a PFS up to 21.3 monthsand 45% PFS at 6 mos. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of 1st-line combination chemotherapy. Based on our promising preliminary results, our aim is to enroll 30-35 metastatic CRC patients. [Table: see text]

An international survey on liver metastases radiotherapy

Background. An international survey of radiation therapy (RT) of liver metastases was undertaken by the Liver Cancer Workgroup of the Third International Consensus on Metastases Workshop at the 2010 American Society for Radiation Oncology (ASTRO) meeting. Material and methods. Canadian, European, Australian, New Zealand and American centers participated in this online survey. The survey had four objectives: 1) to describe the practice patterns for RT of liver metastases; 2) to report on the use of low-dose RT for symptomatic liver metastases; 3) to report on the use of technology; and 4) to describe the regional differences in the management of liver metastases. Results. A total of 69 individuals treating liver metastases with radiotherapy responded to the survey. Regional response rates ranged from 39% to 50%. The primary professional affiliation of all respondents was evenly distributed amongst ASTRO, CARO, ESTRO and TROG/RANZCR. A 36% increase in the average annual number of referrals over the past five years is reported. The majority of referrals were for radical RT. The most common technologies used were 4D-CT (61%), SBRT (55%), IGRT (50%), and/or IMRT (28%). A uniform treatment approach was not found. The most commonly employed radical regimens were 45 Gy in 3 fractions, 40–50 Gy in 5 fractions, and 45 Gy in 15 fractions. Palliative regimens included 20 Gy in 5 fractions, 30 Gy in 10 fractions, 8 Gy in 1 fraction, and 10 Gy in 2 fractions. Conclusions. This survey suggests radiation oncologists will be seeing more referrals for liver RT. The majority of experience in liver metastases RT is with radical SBRT for focal metastases rather than low-dose palliative RT for symptom control. There is significant variation in technology utilization and dose regimens. Prospective studies or registries may allow for comparison of regimens and identification of parameters to optimize patient selection.

InSIRT trial: Single-center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver-predominant metastatic colorectal adenocarcinoma after failure of first-line combination chemotherapy.

685 Background: Liver metastases develop in half of colorectal cancer (CRC) cases and once metastatic ~90% die due to consequences from the hepatic metastases. We are evaluating the aggressive management of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using yttrium-90 radioactive microspheres after evidence of progressive disease following first-line FOLFOX ± bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. We present preliminary data of a phase II study evaluating tumor response rates to SIRT following FOLFOX ± bevacizumab and prior to FOLFIRI. Methods: Subjects with predominant hepatic metastatic CRC despite first-line FOLFOX based therapy ± bevacizumab are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives SIRT followed by second-line FOLFIRI (without bevacizumab) 4-6 weeks after the final SIRT. The primary objective is PFS at 6 mos and secondary objectives include: OS, tumor response rates, and toxicity. Results: To date, 8 metastatic CRC subjects have been treated and 9 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. 4 of 8 subjects (50%) achieved PFS at 6 mos and average TTP is 6.7 mos (0.7-17.3 mos). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 mos median PFS. In 8 subjects with liver predominant metastatic CRC, we have observed 50% PFS at 6 mos. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy. [Table: see text]

Stereotactic Radiotherapy for Liver Metastases

Liver metastases are common in oncologic patients, causing substantial morbidity and mortality. Systemic therapy is now standard palliative treatment for most patients with liver metastases, often providing transient responses and increased overall survival. In selected oligometastatic patients, local treatment can lead to long disease-free intervals and even permanent disease control. Although surgery remains the gold standard of local treatments, most patients will not be appropriate surgical candidates. For these patients, alternate local treatments have been developed. Among these, stereotactic body radiotherapy (SBRT) presents an attractive non-invasive option for selected patients with limited hepatic involvement. This article reviews the development, indications, methods, and results of SBRT in the management of liver metastases.

Value of PET/CT in the Management of Liver Metastases, Part 1

Metastasis is the most common (95%) of liver lesions. Early diagnosis and staging are the keys to treatment planning and prognosis. There is a consistent benefit to the use of PET/CT for detecting hepatic, local, and distant metastases from a variety of primary malignancies, which can contribute to staging and ultimately helps to establish the best course of treatment and to determine prognosis. For colorectal cancer, FDG PET and FDG PET/CT are particularly effective for identification of additional hepatic and extrahepatic metastases, frequently upstaging the tumor stage and affecting management. In addition, PET/CT is very useful in local ablative and systemic therapy assessment and surveillance for liver metastases.