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SAT-03 Neoadjuvant treatment of liver metastases
Abstracts of the 3rd ITLT Essen 2013 / Digestive and Liver Disease 45S (2013) S233–S260
S247
SAT-02
SAT-05
Resection or ablation
Hepatic arterial therapy (HAI) for the treatment of colorectal liver metastases
W.
Prevoo ∗
Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands The golden standard to treat liver metastases from colorectal carcinoma (CRLM) is surgical resection. Is there any indication that one should consider a local minimal invasive treatment instead of surgical treatment? The course of systemic metastatic disease however is that sooner or later recurrence to the liver is very likely. So why do more damage to the liver if a minimal less invasive image guided easy to repeat method is available? Maybe we should consider not to operate in patients especially in cases with a high chance of recurrence. And maybe only chose for repeated ablative treatment sessions? It is still very difficult to compare different treatment methods in prospective studies. In literature there are no comparative studies to be found. But what really happens in daily practice? What choices do we make?
SAT-03
N. Kemeny ∗ Gastrointestinal Oncology Service, Memorial Sloan Kettering Hospital, New York, USA New chemotherapeutic and molecular targeted agents have improved the treatment of colorectal cancer, increasing response rates to 40–60% and survival to 20–24 months. For patients with unresectable liver metastases, in a randomized study using HAI (FUDR/Dex) compared to systemic FU/LV, the median survival was 24.4 vs 20 months, (p 0.0034), respectively. Survival has increased further with the addition of systemic therapy to HAI. Using systemic irinotecan+Oxaliplatin with HAI-FUDR/Dex, the response rate was 91% with a median survival of 41 months, allowing 49% of initially unresectable patients to undergo liver resection. The chance of getting an unresectable patient to resection is listed below. Unresectable Disease-Preop Treatment # Pts Resected Med. survival (mos)
Neoadjuvant treatment of liver metastases C.-H. Köhne ∗ Oldenburg, Germany If resectable, patients with colorectal liver metastases have a curative chance in about 30–40%. Therefore 60–70% of patients will have a recurrence either within the liver or extra hepatic. Data on adjuvant treatment after resection is rare and the number of patients included into those studies low. While a progression free survival prolongation is suggested in these studies no overall survival benefit was demonstrated. It is for this reason that a neoadjuvant approach was studied in the large EORTC EPOC study and patients were randomized to receive FOLFOX followed by surgery or surgery alone. This trial demonstrated a progression free survival advantage for those patients who received neoadjuvant Folfox followed by adjuvant Folfox. In patients with unresectable colorectal metastases confined to the liver or lung, intensive chemotherapy is used in order to downsize the metastases to render them resectable. In centres with an experienced multidisciplinary team about 30–40% of patients become resectable following neoadjuvant chemotherapy. The more efficacious a regimen is, the more likely will patients have a R0-resection. Resectability of liver metastases may therefore be considered as an endpoint in clinical trials. Experienced liver surgeons appear to estimate resectability with a very similar outcome. Conclusions: Neoadjuvant chemotherapy is a useful tool in patients with resectable liver metastases and is mandatory for those with unresectable liver metastases.
SAT-04
Radiation lobectomy vs PVE in HCC R. Salem ∗ Interventional Oncology, Department of Radiology, Northwestern University Chicago, USA The majority of HCCs are not resectable. One of the reasons involves the presence of a small future liver remnant. The mainstay approach to inducing hypertrophy of the liver remnant is with portal vein embolization (PVE). Radiation lobectomy with Y90 is a novel method of achieving the same (or better) results when compared with PVE. The advantage of this technique is that is it: 1) treats the underlying cancer, 2) causes high rates of future liver remnant hypertrophy and, 3) embeds a biologic test of time prior to consideration of resection. This presentation will highlight the outcomes of patients undergoing Y90 with the intent of causing contralateral hypertrophy prior to resection. Outcomes will be compared with PVE.
Folfox Folfox Folfiri Folfoxiri HAI+Systemic Chemo naïve Previously treated HAI-oxali
178 42 40 74 105 44 63* 69*
12% 40% 33% 26%
20 26 – 36.8
57% 44% 24%
51 32 –
Why unresectable 45% 6 or more lesions 61% >6 mets or size 85% >4 or size Diffuse bilateral disease where resection would require resection of both 3 portal veins or 3 hepatic veins Massive liver involvement
*Previously treated. Adjuvant Therapy After Liver Resection (5-year disease free survival) Studies
# Pts
HAI
SYS
P value
MSKCC ECOG Lygidakis Lorenz
156 75 122 186+
55 40 60 20
30 20* 35 12.6*
0.02 0.03 0.0002 NS
*No treatment in control arm; + treated patients.
The most effective treatment for liver metastases is surgical resection; however, 75% of these patients will recur, mostly in the liver. Results of 4 large randomized studies comparing HAI to systemic, demonstrated significant increase in recurrence-free survival in 3 of 4 randomized studies. New trials at MSKCC on more than 100 patients show 4-year survival of 80% after liver resection when adjuvant HAI plus SYS used.
SAT-06
Combination of TACE with systemic therapies: Where are we now? R.C.G. Martin ∗ Surgical Oncology, University of Louisville, USA Purpose: To evaluate the effectiveness of drug-eluting beads loaded with irinotecan (DEBIRI) with concurrent chemotherapy in the treatment of hepatic malignancies. Materials and Methods: A total of 267 patients were enrolled in a prospective, open-label, multicenter, multi-national, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). 60 of these patients received concurrent chemotherapy treatment. Complications were graded by Cancer Therapy Evaluation Program’s Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included. Results: Of those who did not receive concurrent chemotherapy, a total of 207 patients received 364 DEBIRI treatments and 29 doxorubicin treatments (range 1–8 per patient). Of the patients who received concurrent chemotherapy (Xeloda, Erbitux, or another type of chemotherapy), 60 patients received 114 DEBIRI treatments and 8 doxorubicin treatments (range 1–8 per patient). Multivariate analysis identified concurrent chemotherapy with DEBIRI
S247
SAT-02
SAT-05
Resection or ablation
Hepatic arterial therapy (HAI) for the treatment of colorectal liver metastases
W.
Prevoo ∗
Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands The golden standard to treat liver metastases from colorectal carcinoma (CRLM) is surgical resection. Is there any indication that one should consider a local minimal invasive treatment instead of surgical treatment? The course of systemic metastatic disease however is that sooner or later recurrence to the liver is very likely. So why do more damage to the liver if a minimal less invasive image guided easy to repeat method is available? Maybe we should consider not to operate in patients especially in cases with a high chance of recurrence. And maybe only chose for repeated ablative treatment sessions? It is still very difficult to compare different treatment methods in prospective studies. In literature there are no comparative studies to be found. But what really happens in daily practice? What choices do we make?
SAT-03
N. Kemeny ∗ Gastrointestinal Oncology Service, Memorial Sloan Kettering Hospital, New York, USA New chemotherapeutic and molecular targeted agents have improved the treatment of colorectal cancer, increasing response rates to 40–60% and survival to 20–24 months. For patients with unresectable liver metastases, in a randomized study using HAI (FUDR/Dex) compared to systemic FU/LV, the median survival was 24.4 vs 20 months, (p 0.0034), respectively. Survival has increased further with the addition of systemic therapy to HAI. Using systemic irinotecan+Oxaliplatin with HAI-FUDR/Dex, the response rate was 91% with a median survival of 41 months, allowing 49% of initially unresectable patients to undergo liver resection. The chance of getting an unresectable patient to resection is listed below. Unresectable Disease-Preop Treatment # Pts Resected Med. survival (mos)
Neoadjuvant treatment of liver metastases C.-H. Köhne ∗ Oldenburg, Germany If resectable, patients with colorectal liver metastases have a curative chance in about 30–40%. Therefore 60–70% of patients will have a recurrence either within the liver or extra hepatic. Data on adjuvant treatment after resection is rare and the number of patients included into those studies low. While a progression free survival prolongation is suggested in these studies no overall survival benefit was demonstrated. It is for this reason that a neoadjuvant approach was studied in the large EORTC EPOC study and patients were randomized to receive FOLFOX followed by surgery or surgery alone. This trial demonstrated a progression free survival advantage for those patients who received neoadjuvant Folfox followed by adjuvant Folfox. In patients with unresectable colorectal metastases confined to the liver or lung, intensive chemotherapy is used in order to downsize the metastases to render them resectable. In centres with an experienced multidisciplinary team about 30–40% of patients become resectable following neoadjuvant chemotherapy. The more efficacious a regimen is, the more likely will patients have a R0-resection. Resectability of liver metastases may therefore be considered as an endpoint in clinical trials. Experienced liver surgeons appear to estimate resectability with a very similar outcome. Conclusions: Neoadjuvant chemotherapy is a useful tool in patients with resectable liver metastases and is mandatory for those with unresectable liver metastases.
SAT-04
Radiation lobectomy vs PVE in HCC R. Salem ∗ Interventional Oncology, Department of Radiology, Northwestern University Chicago, USA The majority of HCCs are not resectable. One of the reasons involves the presence of a small future liver remnant. The mainstay approach to inducing hypertrophy of the liver remnant is with portal vein embolization (PVE). Radiation lobectomy with Y90 is a novel method of achieving the same (or better) results when compared with PVE. The advantage of this technique is that is it: 1) treats the underlying cancer, 2) causes high rates of future liver remnant hypertrophy and, 3) embeds a biologic test of time prior to consideration of resection. This presentation will highlight the outcomes of patients undergoing Y90 with the intent of causing contralateral hypertrophy prior to resection. Outcomes will be compared with PVE.
Folfox Folfox Folfiri Folfoxiri HAI+Systemic Chemo naïve Previously treated HAI-oxali
178 42 40 74 105 44 63* 69*
12% 40% 33% 26%
20 26 – 36.8
57% 44% 24%
51 32 –
Why unresectable 45% 6 or more lesions 61% >6 mets or size 85% >4 or size Diffuse bilateral disease where resection would require resection of both 3 portal veins or 3 hepatic veins Massive liver involvement
*Previously treated. Adjuvant Therapy After Liver Resection (5-year disease free survival) Studies
# Pts
HAI
SYS
P value
MSKCC ECOG Lygidakis Lorenz
156 75 122 186+
55 40 60 20
30 20* 35 12.6*
0.02 0.03 0.0002 NS
*No treatment in control arm; + treated patients.
The most effective treatment for liver metastases is surgical resection; however, 75% of these patients will recur, mostly in the liver. Results of 4 large randomized studies comparing HAI to systemic, demonstrated significant increase in recurrence-free survival in 3 of 4 randomized studies. New trials at MSKCC on more than 100 patients show 4-year survival of 80% after liver resection when adjuvant HAI plus SYS used.
SAT-06
Combination of TACE with systemic therapies: Where are we now? R.C.G. Martin ∗ Surgical Oncology, University of Louisville, USA Purpose: To evaluate the effectiveness of drug-eluting beads loaded with irinotecan (DEBIRI) with concurrent chemotherapy in the treatment of hepatic malignancies. Materials and Methods: A total of 267 patients were enrolled in a prospective, open-label, multicenter, multi-national, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). 60 of these patients received concurrent chemotherapy treatment. Complications were graded by Cancer Therapy Evaluation Program’s Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included. Results: Of those who did not receive concurrent chemotherapy, a total of 207 patients received 364 DEBIRI treatments and 29 doxorubicin treatments (range 1–8 per patient). Of the patients who received concurrent chemotherapy (Xeloda, Erbitux, or another type of chemotherapy), 60 patients received 114 DEBIRI treatments and 8 doxorubicin treatments (range 1–8 per patient). Multivariate analysis identified concurrent chemotherapy with DEBIRI