Patients with nonresectable colorectal cancer receiving palliative chemotherapy have a 5‐year overall survival rate of about 10%. Liver transplant provided a Kaplan‐Meier–estimated 5‐year overall ...survival of up to 83%. The objective of the study was to evaluate the ability of different scoring systems to predict long‐term overall survival after liver transplant. Patients with colorectal cancer with nonresectable liver‐only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography (PET)‐CT scans from 2 prospective studies (SECA‐I and ‐II) were included. All included patients had previously received chemotherapy. PET‐CT was performed within 90 days of the liver transplant. Overall survival, disease‐free survival, and survival after relapse based on the Fong Clinical Risk Score, total PET liver uptake (metabolic tumor volume), and Oslo Score were compared. At median follow‐up of 85 months for live patients, Kaplan‐Meier overall survival rates at 5 years were 100%, 78%, and 67% in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume–low group, and Oslo Score 0 to 2, respectively. Median overall survival was 101, 68, and 65 months in patients with Fong Clinical Risk Score 0 to 2, metabolic tumor volume–low, and Oslo Score 0 to 2. These selection criteria may be used to obtain 5‐year overall survival rates comparable to other indications for liver transplant.
Based on different scoring systems, colorectal cancer patients with nonresectable liver‐only metastases may obtain Kaplan‐ Meier calculated 5‐year overall survival of 67%‐100% after liver transplantation. See the editorial from Goto and Selzner on page 331.
Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included ...control groups less healthy than the living donor population and have had relatively short follow-up periods. Here we compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11–1.52) for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.
To determine overall survival and disease-free survival in selected patients with nonresectable liver-only colorectal cancer receiving liver transplantation.
Patients with nonresectable colorectal ...cancer receiving palliative chemotherapy has a 5-year overall survival of about 10%. Liver transplantation provided an overall survival of 60% in a previous study (SECA-I). Risk factors for death were carcinoembryonic antigen (CEA) >80 μg/L, progressive disease on chemotherapy, size of largest lesion>5.5 cm, and less than 2 years from resection of the primary tumor to transplantation.
In this prospective (SECA-II) study, we included colorectal cancer patients with nonresectable liver-only metastases determined by computed tomography (CT)/magnetic resonance imaging/positron emission tomography scans and at least 10% response to chemotherapy. Time from diagnosis to liver transplant was required to be more than 1 year.
At a median follow-up of 36 months, Kaplan-Meier overall survival at 1, 3, and 5 years were 100%, 83%, and 83%, respectively. Disease-free survival at 1, 2, and 3 years were 53%, 44%, and 35%, respectively. Overall survival from time of relapse at 1, 2, and 4 years were 100%, 73%, and 73%, respectively. Recurrence was mainly slow growing pulmonary metastases amenable to curative resection. Fong Clinical Risk Score of 1 to 2 at the time of diagnosis resulted in longer disease-free survival than score 3 to 4 (P = 0.044). Patients included in the present study had significantly better prognostic factors than the previous SECA-I study.
Liver transplantation provides the longest overall survival reported in colorectal cancer patient with nonresectable liver metastases. Improved selection criteria give patients with nonresectable colorectal liver metastases a 5-year overall survival comparable to other indications for liver transplantation.
Summary
Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence ...and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA‐I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5‐year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5‐year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5‐year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease‐free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.
Could liver transplantation (LT) offer better survival than liver resection (LR) for colorectal liver metastasis (CRLM) in patients with high tumor load? Tumor load was defined as tumor burden score (TBS), and inclusion criteria were as in SECA‐I trial. Our results show that patients with Oslo score ≤2 and TBS ≥9 could benefit from LT more than LR.
Assessing the balance between survival and recurrence after transplantation for secondary liver tumours should be based on the type of cancer in question. For neuroendocrine liver metastases, high ...recurrence rates are clearly related to reduced long-term survival. For colorectal liver metastases, experience to date indicates that pulmonary recurrence alone has a modest impact on survival outcomes. Further studies focusing on this group of patients will be important for the development of this field of transplant oncology. Liver transplantation for secondary liver tumours should be implemented in accordance with stringent transplant criteria and preferably in the context of prospective trials. Expansion of the donor pool by utilising extended criteria donors and partial liver transplantation could be considered for this indication.
Selected patients with nonresectable colorectal liver metastases benefit from liver transplantation and have acceptable 5-year survival rates. However, allocating full-sized grafts to this group of ...patients is difficult due to the scarcity of grafts. This could be improved by utilizing small partial grafts, which mandates effective strategies to overcome the problems regarding insufficient functional liver mass.
We have developed a protocol incorporating previously reported experiences from living donor transplantation and recent developments in liver surgery, facilitating transplantation of very small liver grafts. At the time of transplantation, segments 1 to 3 are resected in the recipient and orthotopically replaced by a segment 2 to 3 allograft. Portal inflow is modulated by redirecting the portal flow to the graft with concomitant focus on keeping the portal vein pressure below 20 mm Hg. A second-stage hepatectomy is performed as soon as the graft has regenerated to a sufficient volume.
A graft weighing 330 g was transplanted to a 50-year-old man weighing 92 kg, and the portal vein to the right remnant liver was closed. The volume of the liver graft was doubled 2 weeks after the first procedure, and it increased further after the second procedure, with extended right hepatectomy performed at day 23 after transplantation. There were no signs of liver failure or small-for-size syndrome.
The current protocol and ongoing study could represent a possible strategy to increase the availability of liver transplantation to patients with nonresectable liver tumors such as hepatocellular carcinoma and colorectal liver metastases.
The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs).
Patients with nonresectable ...CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated.
In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy.
Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8-60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors.
OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).
Summary
Solid organ recipients have a 2–5 fold increased risk of malignancy compared to the general population. Because of the broader indications for transplantation, it is anticipated that an ...increasing number of organ graft recipients will present with malignancy. There are limited data about responses and tolerance to chemotherapy in solid organ transplanted patients. Twenty‐three of 46 colorectal cancer (CRC) patients with nonresectable liver metastases who had undergone liver transplantation (LT) in three different studies were included. All patients had received chemotherapy both prior to LT and after LT, at recurrence of metastatic CRC (mCRC). Adverse reactions (grades 3–4) and clinical and radiological outcome were retrospectively registered. Overall survival was determined from start of palliative chemotherapy after LT. No graft rejection was observed. Chemotherapy for mCRC was overall well‐tolerated and there was no increased bone marrow toxicity registered after LT; however, mucositis and diarrhea were more frequent in post‐LT chemotherapy. Median overall survival from start of palliative chemotherapy after LT was 13 months. No graft loss was observed when chemotherapy for mCRC was given to LT recipients who had developed nonresectable metastases. Overall, the chemotherapy for mCRC was well‐tolerated, induced responses, and long‐term survival was obtained in some patients.
Summary
Liver transplantation (LT) in selected colorectal cancer (CRC) patients with nonresectable liver‐only metastases may result in 5‐year overall survival of up to about 70–100%. However, the ...majority will have recurrent disease. All patients included in this report were included in prospective studies. Forty‐four out of 56 patients had a relapse, and all 44 patients received treatment for recurrent disease. The organ of the first relapse was lung metastases in 23 of the 44 patients. The first treatment modality of the relapse was the treatment with curative intent in 55.8% of the patients, and chemotherapy was the first treatment administered to 25.6% of the patients. Patients receiving surgery of lung metastases had a 5‐year overall survival of 66.5% from the time of metastasectomy. Patients receiving treatment with curative intent for metastases to other organs had a 5‐year overall survival of 24.8%. Nine of the 44 patients had no evidence of disease (NED) at the end of the follow‐up. Median time of NED in these patients was 54.3 months, and median overall survival from the time of LT was 8.4 years. Because of the high incidence of recurrent disease, these patients should have a systematic long‐term follow‐up since many of the relapses may be treated with curative intent.
The majority of colorectal cancer patients receiving a liver transplant will have a relapse. The lung is the most frequent organ of relapse after liver transplantation in these patients. Many of the pulmonary metastases were resected, with 5‐year overall survival from metastasectomy of 66.5%.
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