| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
EDITORIALS |
From the University of California, San Francisco, San Francisco, California.
Correspondence: Address correspondence to: Alan P. Venook, MD, University of California, San Francisco, 1600 Divisadero, Box 1705, San Francisco, CA 94115; Fax: 415-353-9959; E-mail: Venook{at}cc.ucsf.edu
Tumors in the liver represent both daunting challenges and major opportunities for the treating surgeon and oncologist. The liver is anatomically complicated and very vascular. Liver dysfunction hampers our ability to intervene and yet it is often declining liver function that causes death for patients with hepatic involvement. These features make it a dangerous organ to approach. On the other hand, the liver can regenerate after part of it is removed, it has a dual blood supply, and metastases will sometimes involve the liver but no other organs. These are the features that make it an inviting target for therapeutic innovation.
With these circumstances, it is no wonder that hepatic tumors have been the subject of many clinical endeavors over the years. In particular, technological wizardry has targeted liver tumors. Numerous methods for selectively perfusing and isolating hepatic tumors have been explored, while the means to destroy, ablate, and fry hepatic tumors have proliferated. No fewer than 15 techniques, vascular pumps, ablation implements, needles, and imaging modalities, have been designed to attack hepatic tumors.
For all of this clinical curiosity and activity, however, the impact of these liver-directed therapies, other than on device manufacturers’ bottom line, is poorly understood. The most rigorously studied modality is hepatic intra-arterial (HIA) chemotherapy. HIA probably improves outcome for selected patients with metastatic colorectal cancer to the liver, although any benefits may be outweighed by the complexity of the treatment and the complications related to it. Over the past decade, at least eight randomized trials involving HIA for patients with unresectable or resectable hepatic metastases have been reported.1 Some studies demonstrate improved outcomes with the approach, others do not; it is up to the practitioner to interpret the data and make the determination of how and when to apply the findings, and, in general, this HIA approach is used sparingly by a limited group of clinicians in highly selected patients.
On the other hand, the number of tumor ablation techniques used in practice and the patients being treated with them seems to grow every day. An incomplete list (written at the risk of the wrath of proponents whose techniques are not mentioned) would include cryosurgery, radiofrequency ablation, thermal ablation, internal radiation, and embolic therapies. These, in general, have been incompletely studied, other than for safety, yet there is widespread usage. In general, devices and techniques deemed safe in cancer patients are approvable and often reimbursed even in the absence of evidence that the modality has a substantial impact on patient survival. Clinicians, facing desperate patients with desperate circumstances, are often inclined to apply such treatments, reflecting the perception that any intervention is better than observation, a nothing ventured, nothing gained sort of logic.
The study by Scaife et al.2 in this issue of the Annals of Surgical Oncology represents an example of researchers stepping back from this frenzy of trial and error that has punctuated the use of these techniques. These investigators studied what many practitioners have already decided is safe and feasible, combining multiple approaches for safety and feasibility. And while the results are not stunning, they are a sobering reminder of the uncertainties of the field and how hard it is to move forward.
In this report, the researchers pooled the resources of two major referral centers with programs emphasizing the management of hepatic tumors, the M. D. Anderson Cancer Center in Houston, Texas, and the G. Pascale National Tumor Institute in Naples, Italy. And in conservative fashion, they assessed the safety and feasibility of offering patients with colorectal hepatic metastases combined therapy with ablation and/or hepatic resection and HIA chemotherapy. The safety and feasibility, and indeed, efficacy, of combining resection and HIA chemotherapy are established; no such data existed in support of combining resection and ablation techniques with HIA chemotherapy.
The results? Assuming one applies conservative HIA chemotherapy, it is relatively safe in the hands of these experts, although the technical problems appeared to be more substantial in Italy than in the U.S. Similarly, this report confirms that such multimodal treatment is feasible, and that the therapy can be delivered, at least in highly selected patients being treated by centers with dedicated programs.
But is this complicated approach an improvement? While asking the question of efficacy in a study of safety and feasibility is not usually wise, it is the unavoidable end point that interests most observers. In this instance, the data reported would confirm the prior observations that some selected patients, approximately 30% or so, with colorectal liver metastases will benefit from this sort of aggressive surgical and medical approach. However, the results are not superior, and indeed may seem inferior, to those reported by others using other surgical and chemotherapy interventions.3 Although this may reflect the modest goals of the trial and the heavy pretreatment of most of the patients, particularly those in Europe, the apparent lack of major progress still registers as a disappointing finding.
So do this study and this report move the field forward? Probably yes but not far. While the study was being conducted (1996–2001), two additional chemotherapy drugs, irinotecan and oxaliplatin, assumed prominent positions in the management of these very same patients. The usage of agents like these appears to improve the outcome in the subset of the patients discussed in this report.4 Meanwhile, new techniques, with improved activity and easier application, have become available for the ablation of tumors. Refined imaging has helped better define the optimal patient subsets to be considered for these approaches. Indeed, the technology and treatment, fluoropyrimidine-based chemotherapy, studied by Scaife et al. seems far out of date today, even though it was well conceived and well intended and the study well conducted.
That is why so many leaders and practitioners have taken to offering these treatments to patients, assuming safety and presuming additive efficacy. In the eyes of many in the oncology community and their patients, conducting studies such as the one reported by Scaife et al. merely takes time, uses resources, and answers questions that are already passe. But if we do not ask the questions, we will continue to empirically move forward, and then be forced to take giant steps backwards when we encounter problems. It is a painfully slow process but attending to the details is the only way to prove that our new technologies actually help patients.
Received for publication March 10, 2003. Accepted for publication March 26, 2003.
REFERENCES
| ||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
