A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma.

Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.

Detection of lymph node metastases in lung cancer: comparison of 131I-anti-CEA-anti-CA 19-9 immunoscintigraphy versus computed tomography.

Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anti-carcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of mediastinal staging. Seventeen patients were involved in a prospective, blind study, to compare IS with CT-scan imaging of the mediastinum. Sensitivity and specificity of both methods were analyzed with reference to pathological staging by mediastinal lymph node sampling. IS imaging was not possible in two patients owing to a thyroid uptake and one patient refused surgery. Among the 14 evaluable patients, sensitivity and specificity were 0.83 and 0.12 for IS, and 0.66 and 0.50 for CT-scan, respectively. We used different thresholds of positivity for both methods in order to evaluate the sensitivity-specificity relationship. When compared with that of IS, the area under the receiver operating characteristic (R.O.C.) curves of the CT-scan was bigger. Although one patient had pathologically confirmed N2 with negative CT-scan and positive IS, the results of IS were hampered by a very high level of false positivity. Finally, there was no relationship between positivity of IS and a high serum CEA level. Lack of specificity and the insufficient sensitivity of the iodine-131 anti-CEA-anti-CA 19-9, lead to the conclusion that IS adds weak information to a CT-scan, in the non-invasive mediastinal staging of lung cancer. More efficient radionuclides and markers are needed in the setting of lung cancer staging.

[131I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors.

Dosimetry and therapeutic application of [(131)I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [(131)I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy.MBq(-1). No intolerance or adverse effects were observed after the therapeutic doses (3.3-6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.

Single photon emission computerized tomography (SPECT) for monitoring regeneration of the human liver after partial hepatectomy for secondary tumours.

In 18 patients, the liver volume during regeneration after partial hepatectomy for secondary tumours was estimated by single photon emission computerized tomography (SPECT). Hepatic weight index (HWI) was subsequently calculated to follow evolution of the regeneration as a function of postoperative complications over a 30-day period. In patients with postoperative complications the HWI curves initially rose progressively and either reached a plateau or declined thereafter. The same pattern of HWI evolution was observed in patients with tumour recurrence, which was diagnosed later. On the other hand, in patients without postoperative complications the HWI curves rose continuously. These findings showed that a regenerative response was not the same in patients with or without postoperative complications; whereas in patients with tumour recurrence it could additionally provide prognostic information.

[Cancer of the breast: the return of lymphoscintigraphy?]. / Cancer du sein: le retour de la lymphoscintigraphie?

Lymphoscintigraphy, after arousing great hope in the past in the field of breast cancer, has now been abandoned. The inability of this examination to predict the metastatic status of the nodes, and progress in therapeutic concepts have led to abandoning this technique. However, certain problems encountered by regional irradiation programmes and the work concerning sentinel node detection may bring this technique back into the spotlight. Lymphoscintigraphy may make it possible to adopt an individual approach, case by case, of the lymphatic drainage basins in breast tumors, thus enabling certain patients to benefit from regional irradiation when it would not have been traditionally recommended for this irradiation. Another aspect concerns the problem of the volumes irradiated. Work carried out with lymphoscintigraphy has enabled internal mammary chain nodes to be precisely located. Theses studies show the necessity of adapting the irradiation field to each individual case, but the clinical impact is limited, in the end, by the low recurrence rate in the internal mammary chain area. However, the new techniques of computer merging of scintigraphic and scanner images could enable the spatial position of the nodes in the upper axillary and supraclavicular regions to be determined. This would have, a priori, much wider clinical impact. Lymphoscintigraphic detection of the sentinel node is another field of major interest, but this technique is in competition with staining techniques. This procedure leads to a large reduction in morbidity of axillary surgery in 70% of patients. The use of techniques for detecting micrometastases in the sentinel node opens prospects in terms of prognosis. The qualities of differents radiotracers and different injection sites possible are also discussed.

[Computed gamma-tomographic estimation of a hepatic weight index during liver regeneration]. / Mise au point par gammatomographie computérisée d'un index pondéral hépatique au cours de la régénération du foie.

Single photon emission computed tomography was used to evaluate the total functioning liver mass and the regeneration process after partial hepatectomy. Serial tomographic sections were performed after infusion of 99m Technetium. In studies on dogs and in human beings, computed gammatomography enabled to calculate the liver mass with less than 10 p. 100 error. Hepatic regeneration was studied in 10 patients following resection of 46 to 84 p. 100 of the initial liver mass. The remaining liver mass increased rapidly postoperatively and doubled within 13 to 18 days. The regeneration process followed an exponential curve. Assessment of liver regeneration by this non-invasive technique should be of great help following partial hepatectomy.

[Congenital anomalies of the pyeloureteral junction in children. Multicenter study of 985 anomalies in 883 children]. / Les anomalies congénitales de la jonction pyélo-urétérale chez l'enfant. Etude multicentrique de 985 observations chez 883 enfants.

The authors report a survey of the French Group of Visceral Pediatric Surgery, concerning 985 congenital anomalies of the pyeloureteric junction in 883 children. 67.3% of them are boys. This article stresses the recent improvements in prenatal ultrasonography and diagnosis which is now able to individualize a homogeneous group of asymptomatic children ready to be repaired in the early post-natal period. Early reconstruction is associated with the greatest degree of recovery of renal function. In children, the average age is 4 years 9 months at diagnosis. In 43.6% clinical symptoms suggest an infectious problem. Pain is noted in 35.5% and an abdominal mass is discovered in 13.3%. Excretory urography (IVP), ultrasonography and cystography are still the main investigations to be done in all cases. But it is now necessary to use modern isotopic technics such as DMSA and diuretic DTPA to quantify obstruction with accuracy and follow long-term evolution after treatment. Treatment is surgical and conservative in 81.4%. Almost all of the uretero-pyeloplasties are performed according to the dismembered technic usually with temporary nephrostomy drainage. Renal reduction is reserved only for the redundant and decompensated renal pelvis. Morbidity is low (2.5%) and good results can be expected in about 95% of cases.

Metastatic phaeochromocytoma with a long-term response after iodine-131 metaiodobenzylguanidine therapy.

Iodine-131 metaiodobenzylguanidine ([131I]MIBG), a radiopharmaceutical agent, is used for treating malignant phaeochromocytoma. [131I]MIBG therapy results in a hormone response rate of approximately 50%, but generally it yields only a partial or no tumour response. We present a case of a 46-year-old woman with a familial history of von Hippel-Lindau disease, who was treated with [131I]MIBG for a metastatic phaeochromocytoma involving the lungs, liver and bones. The patient received a cumulative dose of 33.3 GBq (900 mCi) and a complete hormone response was observed, as evaluated on the basis of catecholamine and metanephrine levels. Conventional radiography, computerized tomography and [131I]MIBG scintigraphy indicated that a near-complete tumour regression was achieved, with no evidence of relapse during a 4-year follow-up period. This case thus demonstrates that treatment with [131I]MIBG may lead to a dramatic tumour response in malignant phaeochromocytoma presenting both soft tissue and bone metastases.

Estimation of hepatic volume by SPECT during liver regeneration: an experimental study in an animal model.

To calculate hepatic volume in the dog by single photon emission computerized tomography (SPECT), we determined the limits of the organ by choosing an isocontour on each section. This choice entailed prior calculation of an overestimated pseudovolume. The accuracy of the measurement in the animal then approached that of measurements in vitro. We used the method to monitor hepatic regeneration in the dog after 65% hepatectomy and detected oedema and postoperative trauma, and over a longer timespan, stagnation of regeneration and a secondary drop in hepatic volume.

Phase-I/II radio-immunotherapy study with Iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab')2 in patients with non-resectable liver metastases from colorectal cancer.

Experimental studies in nude mice with human colon-carcinoma grafts demonstrated the therapeutic efficiency of F(ab')2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I-labeled F(ab')2 fragments (131I-F(ab')2) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with 131I-F(ab')2, doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of 131I-F(ab')2 in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophils and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia. The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of 131I-F(ab')2 from the anti-CEA Mab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity.