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Comment: Disseminated cancer—metastases to liver
Inl. J. Radiorion
Oncology
Biel.
Phys..
1976. Vol.
1, pp. 991-992.
Pergamon
Press.
Printcd
in the U.S.A.
COMMENT: DISSEMINATED
CANCER-METASTASES
TO LIVER
ROBERT D. SULLIVAEU’, M.D. Associate ClinicalProfessor of hledicine,
University Irvine, CA 92664. U.S.A.
Metastatic
Ever cancer, Diagwsis,
of California,
Therapy.
This series is concerned with the currently accepted methods for the detection of metastatic liver cancer utilizing the newer techniques of radioisotope imaging and selective angiography; it reviews measures which are directed to the management of proven metastatic liver deposits, i.e. surgery, radiation and therapy and systemic regional chemotherapy. Liver metastases’are a common occurrence in a major proportion of patients with neoplastic diseases. Effective management of diffuse intrahepatic metastases is a most defying and currently uncontrolled problem. Of patients who die from cancer 50-75% have metastases to the liver;’ it is estimated that hepatic insufficiency represents the direct cause of death in 40% of these patients. This is particularly distressing in patients with metastatic colorectal cancer since 25% of those who succumb to the disease have been cured of the primary tumor by surgical resection, only to die of progressive liver metastases.4 Moreover, 15-26% of patients with metastatic breast cancer die from liver involvement; more than 50% have clinically significant involvement of the liver. The mean survival time of patients with breast cancer which is metastatic to the liver is 6 months.2 In a study of 390 patients with untreated hepatic metastases, the progress of cancer within the liver appeared to be the dominant influence on survival despite the presence of metastases in other sites. “Radioisotopic Methods in Diagnosis and Assessment of Liver Metastases” is presented by Drs. Bril1 and Patton. They describe the bases for radionuclide imaging and emphasize the ever-changing techniques and increasingly sophisticated equipment utilized. 991
suggest that liver stans are of value in estimating liver size and shape; they present the pitfalls of differentiating diffuse parenchymal disease from infiltrating neoplasms, i.e. lymphosarcoma. and leukemia from diffuse parenchymal hepatocellular disease: they discuss spleen size as wel1 as the diff erential diagnosis of abnormaiities of radiocolloid distribution, (especially when focal abnormalities are zones of decreased radiocolloid, activity) and the limitations thereof (i.e. lesions of 2.5 cm or less may be missed). They review the sensitivity of liver stans including false positive and false negative interpretations in the detection of liver metastases as described by numerous authors. A comparison of liver scanning with radiotracers of ultrasound with angiography is presented. Quite importantly, the role of serial liver stans in evaluating response to chemotherapy is stressed. One must be cognizant of the wide range of specificity of positive and negative reports of stans in evaluating a single study. The section on “Angiography of Hepatic Neoplasms” is presented in a succinct, clear and condensed fashion by Dr. Bragg. He emphasizes the importante of tumor vascularity as the critical factor in evaluating space occupying lesions, and the importante of the late phase of the angiogram (viz. the portogram). He delineates the role which angiography plays in the diagnosis of metastatic lesions of the liver, the differentiation between primary and secondary tumors, the value of staging of gastrointestinal neoplasm, the information obtained relative to possible surgical extirpation of the tumor and. of inestimable value, the use of angiography as a criterion of antitumor response to treatment by radiation They
992
Radiation Oncology ??Biology 0 Physics
September-October
and chemical therapy. Visceral angiograms are obtained routinely prior to catheter placement for regional infusion therapy of hepatic neoplasms since there is a high incidence of anomalous hepatic arterial blood supply. This information is invaluable in planning catheter placement. A glossary of angiographic terminology is provided together with its import. In the section on “Surgical Approaches to Primary and Metastatic Liver Neoplasms”, Drs. Starzl and Putnam present the anatomie aspects of partial and total hepatectomy with singular clarity. Certainly, their indications for resection of single primary hepatomas are cogent but the data relating to extirpation of metastatic liver tumors is fragmentary and inconclusive. It is true, the authors allude to the scant literature available and the paucity of cases of individual series reported, rendering it virtually impossible to evaluate the surgical treatment of this most common form of metastatic cancer. They emphasize the need for pooled data and for institution of surgical adjuvant chemotherapy programs. The role of liver transplantation is defined cognitively. Drs. Kraut and Earle in the section on “Radiation Therapy’s Role in the Management of Liver Metastases” describe clearly the tissue tolerante of the liver to irradiation and the sequelae resulting from excessive irradiation of the entire organ. However, in selected cases of lymphomas, seminomas and rapidly dividing carcinomas, relatively low-dose irradiation alone may provide palliative effect. This is true especially with the adjuvant use of chemotherapy.
1976, Vol. 1, Numbex 9 and Number 10
“Systemic and Arterial Infusion Chemotherapy for Metastatic Liver Cancer” is reviewed and it is noted that few cooperative clinical trials are currently in progress to evaluate these modalities of therapy. Liver metastases often are used as the “indicator lesion” in studies of anti-cancer drugs on primary cancers arising from various sites. At the present time, 5-fluorouracil remains the most effective chemical agent with a response rate of lO-24% and a duration of response of 3+ months. NO prolongation of survival has been substantiated. Regional cancer chemotherapy involving the continuous arterial infusion of antimetabolite via a catheter inserted directly into the hepatic artery, and thus developing a “portal” of chemotherapy within the liver has resulted in antitumor responses associated with clinical benefit in 35-85% of cases so treated. Prolong ation of survival was noted with median suivival rates of 8.5-15+ months in responders as compared to 2.5-4.5 months in non-responders. This section of “Current Concepts in devoted to “Metastases to the Cancer”, Live?, is directed to the primary physician and to other specialists concerned with the management of patients with liver metastases. An attempt has been made to delineate the magnitude of the problem, present diagnostic modalities in current use and outline specific measures of anticancer therapy. Liver metastases are a most common clinical problem and management spans the three major therapeudisciplines in oncology: tic surgery, radiotherapy and chemotherapy.
REFERJZNCES 3. Jaff e, B.M., Donegan, W.L., Watson, F., ef al.: 1. Ariel, I.M., Pack, G.T.: In intra-arterial Factors influencing survival in patients with chemotherapy for cancer metastatic to the liver. untreated hepatic metastases. Surg. Gynecol. 62 Arch. Surg. 91: 851-862, 1%.5. 2. Bengmark, S., Hafström, L., Olsson, A.: The natura1 history of primary and secondary liver tumors-V. The prognosis for conventionally treated patients with liver metastases from breast cancer. Digestion 6: 321-329, 1972.
Obstet. 127: 1-11, 1%8. 4. Swinton, N., Legg, M., Lewis, G.: Metastasis of cancer of the rectum and sigmoid flexure. Dis. of Colon 7: 273-277, 1964.
Oncology
Biel.
Phys..
1976. Vol.
1, pp. 991-992.
Pergamon
Press.
Printcd
in the U.S.A.
COMMENT: DISSEMINATED
CANCER-METASTASES
TO LIVER
ROBERT D. SULLIVAEU’, M.D. Associate ClinicalProfessor of hledicine,
University Irvine, CA 92664. U.S.A.
Metastatic
Ever cancer, Diagwsis,
of California,
Therapy.
This series is concerned with the currently accepted methods for the detection of metastatic liver cancer utilizing the newer techniques of radioisotope imaging and selective angiography; it reviews measures which are directed to the management of proven metastatic liver deposits, i.e. surgery, radiation and therapy and systemic regional chemotherapy. Liver metastases’are a common occurrence in a major proportion of patients with neoplastic diseases. Effective management of diffuse intrahepatic metastases is a most defying and currently uncontrolled problem. Of patients who die from cancer 50-75% have metastases to the liver;’ it is estimated that hepatic insufficiency represents the direct cause of death in 40% of these patients. This is particularly distressing in patients with metastatic colorectal cancer since 25% of those who succumb to the disease have been cured of the primary tumor by surgical resection, only to die of progressive liver metastases.4 Moreover, 15-26% of patients with metastatic breast cancer die from liver involvement; more than 50% have clinically significant involvement of the liver. The mean survival time of patients with breast cancer which is metastatic to the liver is 6 months.2 In a study of 390 patients with untreated hepatic metastases, the progress of cancer within the liver appeared to be the dominant influence on survival despite the presence of metastases in other sites. “Radioisotopic Methods in Diagnosis and Assessment of Liver Metastases” is presented by Drs. Bril1 and Patton. They describe the bases for radionuclide imaging and emphasize the ever-changing techniques and increasingly sophisticated equipment utilized. 991
suggest that liver stans are of value in estimating liver size and shape; they present the pitfalls of differentiating diffuse parenchymal disease from infiltrating neoplasms, i.e. lymphosarcoma. and leukemia from diffuse parenchymal hepatocellular disease: they discuss spleen size as wel1 as the diff erential diagnosis of abnormaiities of radiocolloid distribution, (especially when focal abnormalities are zones of decreased radiocolloid, activity) and the limitations thereof (i.e. lesions of 2.5 cm or less may be missed). They review the sensitivity of liver stans including false positive and false negative interpretations in the detection of liver metastases as described by numerous authors. A comparison of liver scanning with radiotracers of ultrasound with angiography is presented. Quite importantly, the role of serial liver stans in evaluating response to chemotherapy is stressed. One must be cognizant of the wide range of specificity of positive and negative reports of stans in evaluating a single study. The section on “Angiography of Hepatic Neoplasms” is presented in a succinct, clear and condensed fashion by Dr. Bragg. He emphasizes the importante of tumor vascularity as the critical factor in evaluating space occupying lesions, and the importante of the late phase of the angiogram (viz. the portogram). He delineates the role which angiography plays in the diagnosis of metastatic lesions of the liver, the differentiation between primary and secondary tumors, the value of staging of gastrointestinal neoplasm, the information obtained relative to possible surgical extirpation of the tumor and. of inestimable value, the use of angiography as a criterion of antitumor response to treatment by radiation They
992
Radiation Oncology ??Biology 0 Physics
September-October
and chemical therapy. Visceral angiograms are obtained routinely prior to catheter placement for regional infusion therapy of hepatic neoplasms since there is a high incidence of anomalous hepatic arterial blood supply. This information is invaluable in planning catheter placement. A glossary of angiographic terminology is provided together with its import. In the section on “Surgical Approaches to Primary and Metastatic Liver Neoplasms”, Drs. Starzl and Putnam present the anatomie aspects of partial and total hepatectomy with singular clarity. Certainly, their indications for resection of single primary hepatomas are cogent but the data relating to extirpation of metastatic liver tumors is fragmentary and inconclusive. It is true, the authors allude to the scant literature available and the paucity of cases of individual series reported, rendering it virtually impossible to evaluate the surgical treatment of this most common form of metastatic cancer. They emphasize the need for pooled data and for institution of surgical adjuvant chemotherapy programs. The role of liver transplantation is defined cognitively. Drs. Kraut and Earle in the section on “Radiation Therapy’s Role in the Management of Liver Metastases” describe clearly the tissue tolerante of the liver to irradiation and the sequelae resulting from excessive irradiation of the entire organ. However, in selected cases of lymphomas, seminomas and rapidly dividing carcinomas, relatively low-dose irradiation alone may provide palliative effect. This is true especially with the adjuvant use of chemotherapy.
1976, Vol. 1, Numbex 9 and Number 10
“Systemic and Arterial Infusion Chemotherapy for Metastatic Liver Cancer” is reviewed and it is noted that few cooperative clinical trials are currently in progress to evaluate these modalities of therapy. Liver metastases often are used as the “indicator lesion” in studies of anti-cancer drugs on primary cancers arising from various sites. At the present time, 5-fluorouracil remains the most effective chemical agent with a response rate of lO-24% and a duration of response of 3+ months. NO prolongation of survival has been substantiated. Regional cancer chemotherapy involving the continuous arterial infusion of antimetabolite via a catheter inserted directly into the hepatic artery, and thus developing a “portal” of chemotherapy within the liver has resulted in antitumor responses associated with clinical benefit in 35-85% of cases so treated. Prolong ation of survival was noted with median suivival rates of 8.5-15+ months in responders as compared to 2.5-4.5 months in non-responders. This section of “Current Concepts in devoted to “Metastases to the Cancer”, Live?, is directed to the primary physician and to other specialists concerned with the management of patients with liver metastases. An attempt has been made to delineate the magnitude of the problem, present diagnostic modalities in current use and outline specific measures of anticancer therapy. Liver metastases are a most common clinical problem and management spans the three major therapeudisciplines in oncology: tic surgery, radiotherapy and chemotherapy.
REFERJZNCES 3. Jaff e, B.M., Donegan, W.L., Watson, F., ef al.: 1. Ariel, I.M., Pack, G.T.: In intra-arterial Factors influencing survival in patients with chemotherapy for cancer metastatic to the liver. untreated hepatic metastases. Surg. Gynecol. 62 Arch. Surg. 91: 851-862, 1%.5. 2. Bengmark, S., Hafström, L., Olsson, A.: The natura1 history of primary and secondary liver tumors-V. The prognosis for conventionally treated patients with liver metastases from breast cancer. Digestion 6: 321-329, 1972.
Obstet. 127: 1-11, 1%8. 4. Swinton, N., Legg, M., Lewis, G.: Metastasis of cancer of the rectum and sigmoid flexure. Dis. of Colon 7: 273-277, 1964.