Preoperative Chemotherapy

Initial chemotherapy for potentially resectable liver metastases

Commentator: STEVEN ALBERTS, MD

Comment:

The data on initial chemotherapy for potentially resectable liver metastases are all retrospective. The data from René Adam suggest that patients with progressive disease during chemotherapy who are still able to undergo a resection don’t fare as well. Eradicating some of the micrometastatic disease up front might help increase the chances of controlling disease after the surgery.

Chemotherapy and liver regeneration

Commentator: MICHAEL CHOTI, MD

Comment:

If you plan to treat with neoadjuvant chemotherapy in the setting of portal vein embolization, consider administering a few cycles of chemotherapy to evaluate response while you are waiting for the liver to hypertrophy. The chemotherapy may keep the tumor in check and a few studies have shown that liver regeneration is not inhibited by chemotherapy.

The use of neoadjuvant therapy for patients with periportal node disease

Commentator: MICHAEL CHOTI, MD

Comment:

I would be more inclined to use neoadjuvant chemotherapy in the setting of resectable disease with positive periportal nodes. If someone has initially resectable disease with periportal node involvement, I think one could still perform surgery followed by chemotherapy or use chemotherapy first, but I would be more inclined to offer chemotherapy because the tumor biology is more aggressive. If the patient doesn’t respond or if other lesions develop, you have spared the patient from unnecessary surgery.

Preoperative chemotherapy: Relationship of response to prognosis

Commentator: NICHOLAS PETRELLI, MD

Comment:

Patients with resectable disease who respond to preoperative chemotherapy fare better than those whose disease may progress during chemotherapy but still have resectable disease. Patient survival is better if they respond and undergo resection than if the disease progresses and then they undergo resection.

Indications for preoperative chemotherapy versus up-front resection

Commentator: JOHN PRIMROSE, MD

Comment:

Based on the results of the EPOC trial, our service has moved toward using chemotherapy as an initial treatment approach. In a sense, it makes the treatment scheduling and treatment decision-making a lot simpler. If the patient has colorectal liver metastasis, they receive chemotherapy. If they have advanced liver metastases, are not operable, they receive chemotherapy. If they are potentially or borderline operable, they receive chemotherapy. Basically, everybody will receive chemotherapy, and we see what can be done after three months. If they are inoperable, they will be treated to best response and then reassessed by our multidisciplinary team to see if their disease is resectable.

Occasionally, we avoid the use of chemotherapy for certain patients such as older patients with good-prognosis disease (eg, a solitary metastasis that’s a couple of years out from the primary resection). Often, we discuss it with the patient, but mostly elect to take the liver tumor out and not receive prior chemotherapy, because often for elderly patients, they tolerate surgery much better than they tolerate chemotherapy. You should base your decision on the individual, but the general strategy now is to initiate chemotherapy for all patients.

Disease progression during preoperative treatment for resectable metastases

Commentator: JOHN PRIMROSE, MD

Comment:

René Adam’s group published data concerning disease progression during preoperative treatment for resectable metastases. Their view is that patients whose disease progresses during chemotherapy have a bad prognosis. I have a patient who is in this exact situation. He received three months of chemotherapy and, on the follow-up scan, had hundreds of metastases in the liver. There is no way that patient is curable by an operation. The disease was already there, and he responded poorly to chemotherapy, so I don’t think you’re denying too many patients the possibility of a curative resection by administering chemotherapy first. I think it is important to perform a three-month scan, because it is still possible to offer surgery to patients whose disease is progressing but remains operable. But in general, I think these patients have a bad outlook.

Implications of a complete radiologic response to neoadjuvant chemotherapy

Commentator: JOHN PRIMROSE, MD

Comment:

If you obtain a complete response to preoperative chemotherapy in the liver within a circumscribed area — for instance, all in the right lobe — we would take out a section and submit it to the pathologist. In most cases, they will find nests of tumor within the liver. The difficult problem for liver surgeons is a situation in which a patient has bilateral disease and awkwardly placed metastases that disappear with chemotherapy. Whereas before chemotherapy, you could have located them and excised them, but now there is nothing to see — that is the problem. If we’re in that situation, we do the best we can. We’ll take out the areas that contained disease. We may leave some areas that also contained disease, because they’re awkward to resect. Sometimes, at best, the oncologists don’t succeed particularly well at reducing the size of liver metastases before surgery, because if you make them undetectable, it makes the surgeon’s job quite difficult. It is all about working closely with your medical oncologist and often operating before the patient has achieved a maximum response, as this is the easiest way of getting the disease out.

Chance of converting initially unresectable liver metastases using neoadjuvant therapy

Commentator: STEVEN CURLEY, MD

Comment:

Based on published data, which our experience mirrors closely, there’s roughly a 20 percent probability that neoadjuvant chemotherapy will convert an unresectable situation to resectable — so a one-in-five chance. The number has increased slightly over time. Initially, in René Adam’s experience, the chance of conversion was about 13 percent, and then it increased to 16 percent. More recent experience, including ours at MD Anderson, has been at about 20 percent. I tell patients that neoadjuvant treatment does not guarantee that they will become resectable. They all understand that resection offers their best chance for long-term survival, but we let them know that we may need to use more than one type of chemotherapy. We may use other local-regional therapies. We have occasionally even used focal radiation therapy, either an intensity modulated radiation therapy or a proton beam approach, if we have a single lesion that is problematic in order to provide an adequate margin between critical vascular or biliary tract structures.

Neoadjuvant conversion therapy

Commentator: STEVEN CURLEY, MD

Comment:

FOLFOX has become our first-line therapy for neoadjuvant therapy. FOLFIRI, we know, can cause problems with the liver. If we have a patient that has a slight chance of having a resection, we use an oxaliplatin-based regimen, rather than irinotecan-based one, because steatohepatitis has been associated with irinotecan. We do not feel the use of bevacizumab increases the risk of perforation of the colon. We are able to proceed with bevacizumab in these patients without a high risk.

Indications for neoadjuvant therapy

Commentator: AXEL GROTHEY, MD

Comment:

In patients who present with synchronous primary and metastatic disease, I tend to offer neoadjuvant therapy because we don’t know anything about the biology of the tumor or its sensitivity to chemotherapy. We have only one snapshot in time, unlike a patient who presents with Stage II or III colon cancer and then two or three years later returns with resectable liver metastasis. In the later, we know it took years to develop metastases and in those patients, I might use only postoperative therapy. Of course, other factors must be taken into consideration also.

Another scenario, which is quite common, is the patient with Stage III colon cancer who recurs within half a year or a year after adjuvant FOLFOX/chemotherapy. This patient would appear to have disease somewhat resistant to FOLFOX, so preoperative therapy with FOLFIRI establishes whether that is an effective alternative. If they don’t respond to FOLFIRI, then I don’t administer postoperative therapy, but at least I’ve spared that patient unnecessary treatment.

Time to recurrence and repeat resection

Commentator: ALAN VENOOK, MD

Comment:

Time to recurrence is definitely a prognostic factor. As far as being aggressive in resecting, I view six months as tenuous — that’s unfavorable. For patients with disease recurrence between one year and 18 months, I think the prognosis is more favorable. To me, recurrence after more than two years is a favorable view and that’s a patient I pull out all the stops for. I act less aggressively with patients who experience recurrence quickly — that’s my approach, but it doesn’t mean the patients will agree with my recommendations.

Copyright © 2008-2009 Research To Practice. All Rights Reserved.