Vincent P. Chuang

Osteosarcoma: Intra‐arterial treatment of the primary tumor with cis‐diammine‐dichloroplatinum II (CDP): Angiographic, pathologic, and pharmacologic studies

Intra‐arterial CDP was utilized to treat the primary tumor in 11 pediatric patients with osteosarcoma and in one with malignant fibrous histiocytoma. The investigation commenced with a phase I‐II pilot study in four osteosarcoma patients. A dose of 150 mg/m2 was found to be safe and effective in producing a clinical response. This was followed by a definitive study in the remaining seven osteosarcoma patients and in the one malignant fibrous histiocytoma patient. The results were assessed by specific clinical, pharmacologic, radiographic and pathologic criteria. The overall response in the definitive study was 50% with two patients exhibiting total tumor destruction. The success of intra‐arterial CDP was attributed to its ability to achieve high local drug concentration and tumor penetration. This was demonstrated by pharmacologic studies.

Intracarotid infusion of cis‐diamminedichloroplatinum in the treatment of recurrent malignant brain tumors

Thirty‐five patients with malignant brain tumors (23 with primary brain tumors and 12 with brain metastases) progressing after cranial irradiation chemotherapy received cisplatin, 60 to 120 mg/m2, into the internal carotid artery by a transfemoral approach. Courses of therapy were repeated every 4 weeks. Therapeutic evaluation was performed monthly using the CT scan of the brain and clinical neurologic examination. Thirty patients were evaluable for response. Of 20 evaluable patients with primary malignant brain tumors, 6 responded to therapy and 5 had stable disease. The median time to tumor progression for responding patients was 33 weeks, for stable patients 16 weeks, and 13 weeks for all patients. Five of 10 evaluable patients with brain metastases responded to intracarotid cisplatin, and 2 patients had stable disease. The estimated median time to progression for responding patients was 30+ weeks and 12+ weeks for patients with stable disease. Side effects included seizures in 5 courses, mental agitation and motor restlessness in 1, and transient hemiparesis in 7. One patient may have had a drug‐related death, and one patient appeared to develop encephalopathy after treatment. Five patients had clinical deterioration in vision; in two patients it was bilateral. Intracarotid cisplatin has definite activity in patients with malignant primary brain tumors and in patients with brain metastases. The recommended starting dose for intracarotid cisplatin is 60 to 75 mg/m2. At this dose level side effects are uncommon, but includes the risk of neurologic and retinal toxicity.

Percutaneous Hepatic Arterial Infusion (HAI) of Mitomycin C and Floxuridine (FUDR): An Effective Treatment for Metastatic Colorectal Carcinoma in the Liver

The response rate of metastatic colorectal carcinoma confined to the liver to HAI of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HAI to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m2 administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography, and radionuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5‐FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapyrelated complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment.

Selective Hepatic Arterial Chemoembolization for Liver Metastases in Patients with Carcinoid Tumor or Islet Cell Carcinoma

In many patients with liver metastases from islet cell or carcinoid tumor, vascular occlusion therapy results in prolonged control of symptoms, biochemical response, and also tumor regression. Chemotherapy agents were added to evaluate safety and efficacy. Thirty patients with liver metastases from either carcinoid tumor or islet cell carcinoma underwent sequential vascular occlusion therapy combined with chemotherapeutic agents. In patients with carcinoid tumor, a combination of cisplatin (150 mg) and doxorubicin (50 mg) was used. In patients with islet cell carcinoma, a combination of 5-fluorouracil (350 mg) and streptozotocin (1000-2000 mg) was used. Sixteen patients had carcinoid tumor and 14 had islet cell carcinoma. Biochemical response was observed in 12 of 16 (75%) carcinoid patients and 9 of 10 (90%) islet cell patients. The overall partial response rate was 37% (11/30 patients). Partial response occurred in 4 of 16 (25%) patients with carcinoid tumor and 7 of 14 (50%) with islet cell carcinoma. The median duration of partial responses was 24 months (range, 6-63+ months). The median survival of all patients was 15 months (range, 2-67+ months). No treatment-related deaths occurred. Our data suggest that the addition of these chemotherapeutic agents to vascular occlusion, although safe, has no additional benefit.

Phase I‐II trial of percutaneous intra‐arterial Cis‐diamminedichloro platinum (II) for regionally confined malignancy

Forty‐nine patients with regionally confined recurrent malignancy were treated with intra‐arterial cisdiamminedichloro platinum II in a Phase I‐II trial. A safe starting dose of 120 mg/m2 was established. An overall response rate of 45% was noted with significant responses observed among patients with melanoma, sarcoma, breast carcinoma, and neuroblastoma. Side effects included transient renal and bone marrow toxicity as well as neurotoxicity and ototoxicity (6%), the latter usually with residual damage. The rational basis and advantages of treatment with intra‐arterial cis‐platinum are discussed.

THE PALLIATIVE ROLE OF HEPATIC ARTERIAL INFUSION AND ARTERIAL OCCLUSION IN COLORECTAL CARCINOMA METASTATIC TO THE LIVER

Fifty-five patients with metastatic colorectal carcinoma confined to the liver were treated with hepatic arterial infusion of floxuridine and mitomycin C. Tumour response rate was 43.4% and median overall survival was 11 months. Prolonged survival was associated with intentional or inadvertent occlusion of the hepatic artery. The median survival of twenty-four patients with arterial occlusion (15 months) was significantly higher than that of thirty-one patients without arterial occlusion (8 months).

Carcinoid Tumors: Imaging Procedures and Interventional Radiology

Abstract. The hypervascular nature of carcinoid tumors and their metastases allows a more aggressive role by the radiologist in diagnosis and interventional management. Double-contrast gastrointestinal studies still best define the primary neoplasms. Appendiceal tumors, the most frequent site of carcinoids, frequently escape radiologic detection until large enough to be discovered by computed tomography (CT). Superior mesenteric arteriography of the small bowel and cecum is useful when the scanning procedures are not revealing. The “spokewheel” configuration of the desmoplastic mesenteric masses and lymph node metastases are best seen by CT, whereas hepatic metastases can be demonstrated by CT, CT-angioportography (CTAP), ultrasonography (US), magnetic resonance imaging (MRI), and octreotide scintigraphy. Percutaneous needle biopsy with radiologic guidance confirms the diagnosis of carcinoid tumors and their metastases. Hepatic arteriography is frequently performed in preparation for hepatic embolization or chemoembolization. Hepatic vascular occlusion therapy, the procedure of choice for the management of inoperable carcinoid liver metastases, results in a partial response in at least 50% of patients and a mortality rate of 5%. Chemoembolization with microencapsulated cytotoxic agents and direct percutaneous ethanol injection should also be considered for the treatment of liver metastases.

Angioinfarction plus nephrectomy for metastatic renal cell carcinoma--an update.

We treated 100 patients with metastatic renal cell carcinoma by angioinfarction of the primary tumor followed by radical nephrectomy. Of the patients 88 also received postoperative parenteral progesterones. We achieved an over-all response rate of 28 per cent (complete regression of all metastatic lesions in 7 patients, regression greater than 50 per cent in 8 and stabilization for at least 1 year in 13). Patients with parenchymal pulmonary metastases only have the best survival rate (64 per cent at 1 year) and are most likely to benefit from angioinfarction and nephrectomy. The presence of hilar or mediastinal adenopathy, pleural effusion or nonpulmonary metastases confers a worse prognosis. These patients do not appear to survive longer with preoperative angioinfarction than if treated by nephrectomy alone. Our data demonstrate that it is critically important to stratify patients by site and volume of disease when results are reported and compared for any patient undergoing treatment for metastatic renal cell carcinoma.

Intraarterial cis‐platinum for patients with inoperable skeletal tumors

Twenty‐three patients with inoperable skeletal tumors were treated with intraarterial cis‐platinum prior to attempted surgery. The antitumor effect of intraarterial cis‐platinum was monitored clinically by radiologic imaging techniques and, whenever possible, evaluated histopathologically by examination of surgical or biopsy tumor specimens. Objective responses were noted in 12 patients (52%) and included 2 complete, 7 partial and 3 less‐than‐partial remissions lasting from 14 to 70 weeks. Limb‐saving surgery or hemipelvectomy became subsequently feasible in four and one patients respectively. Preoperative intraarterial cis‐platinum is a safe procedure which might be used effectively in combination with other, more conventional postoperative adjuvant chemotherapy against skeletal tumors.

Radiation-induced arteritis

Injuries to human vessels in various anatomic sites exposed to therapeutic doses of radiation have shown a remarkably consistent pattern including the following findings: (1) subendothelial connective tissue proliferation; (2) disruption of the elastic lamina; (3) accumulation of intimal and subintimal fibrinoid substances; (4) degeneration of smooth muscle; (5) dense fibrosis of the adventitia; (6) aggregates of foamy histiocytes in the damaged wall; and (7) obliteration of vasa vasorum, z,3 The mechanism of delayed radiation injury of vessels has been hypothesized as endothelial cell damage and the resultant destruction of the microcirculation. 4 In smaller arteries or arterioles, less than 100 ixm, delayed postradiation changes consist of subendothelial fibrosis, subendothelial foam cells, hyaline medial change, and adventitial fibrosis. Obliteration of the arteriolar lumen is observed in advanced cases. In medium-sized arteries, 100-500/xm, accumulation of foam ceils in the subendothelial and