1977, Vol. 2. pp. 129-132.
in the ~S.A.
0 Brief Communication
BABU PRASAD, M.D.,f’ MYUNG-SOOK LEE, M.D.S and FRANK R. HENDRICKSON,M.D.§ Department
of Therapeutic Radiology, Rush-Presbyterian-St. Luke’s Medical Center, 1753 West Congress Parkway, Chicago, IL 60612, U.S.A.
This paper presents the study of liver metastases and the role of radiation therapy in its management. A total of 27 patients were treated in the Radiation Therapy Department of Rush-Presbyterian-St. Luke’s Medical Center between January 1973 and March 1975. The site of primary lesion, histology and interval between the detection of primary and liver metastases were studied in each case. The present study shows that liver irradiation is an effective way of managing patients with symptomatic liver metastases. Our study suggests selection of non-terminal patients for therapy. Roughly 70% of the total series of patients or 95% of the group completing therapy showed symptomatic relief of pain. Jaundice and ascites improved in a small group as well. More than half of the patients with subjective improvement experienced regression in the liver size. No definite conclusion can be drawn about the effect of therapy on liver functions. The survival of patients is probably unchanged by therapy. The average survival since therapy was found to be 4 months. Irradiation,
to treat the liver metastases in an attempt to produce ischaemic necrosis of the tumor. Although a few patients have benefited, the tumor may establish collateral circulation. Hepatic artery ligation and post operative chemotherapy6 also have been described recently with a 57% symptomatic improvement and a mean survival of 27 weeks in patients with colon primaries. Intrahepatic arterial infusion of the chemotherapeutic drug, 5Fluorouracil has been attempted in the past. Ansfield’ reported 60% improvement rate in a study of 113 patients with liver metastases. However, he has also described high morbidity, complications and even mortality associated with this procedure. The present study shows that liver irradiation is an effective way of managing patients
Often, patients with liver metastasis initially have gastro-intestinal symptoms such as nausea, anorexia, and later develop jaundice, ascites, fever and pain in the upper abdomen. Management of these patients requires relief of these problems. The value of partial hepatectomy is limited to solitary metastases and cannot be extended for multiple metastases in one or both lobes of the liver. Systemic chemotherapy might be of value in small groups of patients with metastasis which result from breast cancer or lymphoma. There is no specific chemotherapeutic agent available which is effective especially in colon carcinoma. Hepatic artery ligation alone’ has been used iResident. SAssistant Professor. $Professor and Chairman.
Acknowledgment-The authors convey their sincere thanks to Ms. Mary J. Mitchell for typing the manuscript. 129
Radiation Oncology 0 Biology 0 Physics
with symptomatic liver metastases. Liver irradiation was not used widely in the past, since its value was not recognized and the liver was thought to be a radiosensitive organ. Liver tolerance now has been well established from the experience of liver irradiation in patients with lymphoma and from total abdominal irradiation for patients with ovarian cancer. In a series of 40 patients, Ingold et al.’ have shown that doses of 3000 to the entire liver in 3 weeks are relatively safe. Beyond this, there appears to be a relationship between the radiation dose and liver damage. Previous workers have stressed the role of radiation therapy of the liver for symptomatic metastases. Phillips et al.“ have observed symptomatic relief in 26 of 36 patients treated and improvement in liver functions in 17 patients. Evidence suggestive of liver damage was found in only one questionable instance at a dose of 3500rad to the entire liver. More recently, Maischeider and Kazem5 described the use of 2500rad given in 3 weeks for palliation of hepatic metastases. While only 11 patients were included, 8 had good respones and another 2 had moderate relief of symptoms. The experience with 27 patients who were treated in the Radiotherapy Department of Rush-Presbyterian-St. Luke’s Medical Center, between January 1973 and March 1975 was reviewed. There were 13 males and 14 females. The age varied from 26 to 77 years with an average of 58 years. Analysis of the primary site in our series revealed the gastro-intestinal tract as common site. The common histology was adenocarcinema. Tables 1 and 2 show details of primary sites and histological diagnosis. Histology was reviewed in 4 patients with bronchogenic carcinoma; 3 were found to be anaplastic type, of which 2 were oat cell and 1 was large cell carcinoma. Table 1. Primary site Colon and rectum Stomach Gall bladder Pancreas
9 2 1
Breast Kidney Ovary
Lymph nodes Unknown
1 1 4
1977, Volume 2, No. 1 and No. 2
Table 2. Histology Adeno Ca Anaplastic Hodgkin’s Malignant carcinoid Leiomyosarcoma Unknown
-18 -5 -1 -1 -1 -1
The liver metastases were diagnosed at the initial evaluation in 12 patients. In another 14 patients, the average interval between the detection of primary and hepatic metastases was 28 months. In patients with lung cancer, liver metastases were discovered after a short interval of 3 months. The interval was found to be 8 months in patients with colon cancers. In a single patient with a malignant carcinoid tumor the interval was delayed as long as 1.5 years: this generally agrees with the long natural history of these tumors. Solitary organ involvement of the liver was seen only in 5 patients, while 17 patients had multiple organ metastases such as bones, lungs and brain. A total of eleven patients were referred after failure to respond to different chemotherapeutic agents. A total of 8 patients received chemotherapy following hepatic irradiation. The most frequently used drug was 5-Fluorouracil. Cyclophosphamide, melphalan or a combination of these was used less frequently. The radiation field included the liver as determined by palpation and percussion. In 7 patients, therapy was discontinued either because of terminal stage of the disease or death of the patient. This group received 600-1600 rad to the liver in l-2 weeks. Twenty patients completed their planned therapy and received a dose varying from 1900 to 3100 rad given in 2.5-4 weeks. The average dose to the liver was estimated to be about 2500rad in 3-3.5 weeks. Opposing portals were used frequently, but in a few cases anterior and right lateral fields with or without wedge filters were employed. Considering all 27 patients, 19 (70%) has symptomatic relief of pain. Excluding 7 patients in whom therapy was discontinued, symptomatic improvement was noted in 19 of 20 patients (95%). Pain relief appeared during
Irradiation of hepatic metastases 0 B. PRASAD et al.
Table 3. Effects of therapy on symptoms Symptoms
No. with symptoms
Pain in right upper quadrant or upper abdomen Jaundice Anorexia Ascites
7 9 8
2 7 4
3 2 -
Table 4. Effects on liver functions No. improved Alkaline phosphatase Total bilirubin Latic dehydrogenase (L.D.H.) Serum Glutamic oxaloacetic transaminase (S.G.O.T.)
the therapy in some, while in others, it occurred 2-3 weeks later. In a small group of patients jaundice and ascites improved as well. Table 3 summarizes the effects of therapy on symptoms. Considering the 19 patients with subjective improvement, in 11 the liver size regressed from 3 to 6 cm, in 3 patients liver size increased, while in 3 others, it was unchanged. No definite conclusions can be drawn from this study about the effect of therapy on liver functions. In some of the 7 terminal patients in whom therapy was discontinued worsening of liver functions seemed to occur until their death. In 14 patients serial liver functions which were performed during and following therapy were available. The results are shown in Table 4. Pre-therapy liver scans were performed on a large number of patients and were positive for multiple lesions in one or both lobes of liver. No follow-up scans were available. The survival of patients is probably un-
No. worse No. unchanged
changed by therapy. The 7 terminal patients died within 14 days after completion of therapy. In only 2 of these autopsy findings were available and were found to have disseminated disease. Among the 19 with subjective improvement, average survival since therapy was 4 months. Although this is a retrospective study on a small number of patients, certain definite conclusions can be drawn. 1. Liver irradiation is valuable for palliation of symptomatic liver metastases. Our study favors selection of non-terminal patients for therapy. 2. Treatment is done with no significant morbidity or complication to the patient. We have not seen radiation hepatitis, since doses required for palliation are low and survival is short. 3. Prospective study with careful serial evaluation of liver size, liver functions and scans has been started.
REFERENCES 1. Almersjo, 6., Bengmark, S., Rundenstam, C.M., Hafstrom, L.O.: Evaluation of hepatic dearterialization in primary and secondary cancer of the liver. Am. J. Surg. 124: 5-9, 1972. 2. Ansfield, F.J.: Zntra-arterial Infusion, with 5Fu:
2nd Edn. Springfield, Ill., Charles C. Thomas, 1973, pp. 247-252. 3. Ingold, J.A., Reed, G.B., Kaplan, H.S., Bagshaw, M.A.: Radiation hepatitis. Am. J. Roentgenol. 93: 200-208, 1965. 4. Phillip, R., Karnofsky,
Radiation Oncology 0 Biology 0 Physics
Nickson, J.J.: Roentgen therapy of hepatic metastases. Am. J. Roent. Rad. Therapy 71: 826834, 1954. 5. Turek-Maischeider, A., Kazem, I.: Palliative irradiation for liver metastases. J. Am. Med. Assoc. 232: 625-628,
1977, Volume 2, No. 1 and No. 2
6. Sparks, F.C., Mosher, M.B., Hallauer, W.C., Silverstein, M.J., Range, I.D., Passaro, Jr., E.: Hepatic artery ligation and post-operative chemotherapy for hepatic metastases: clinical and pathophysological results. Cancer 35: 10741082, 1975.