Long-term renal function after treatment for malignant germ-cell tumours.

OBJECTIVE: To evaluate prospectively renal function in patients with malignant germ-cell tumours (MGCTs) >10 years after retroperitoneal lymph node dissection alone (RPLND), radiotherapy alone (RAD) or different schedules of cisplatin-based chemotherapy with or without surgery/radiotherapy (CHEM). PATIENTS AND METHODS: In 85 patients, three groups were identified: RPLND, 14; RAD, 18; CHEM, 53, with subdivision of the latter group according to the cumulative cisplatin dose or the additional use of radiotherapy. Renal function was determined by 131Iodine Hippuran clearance or 99m DTPA glomerular filtration rate, and was assessed before treatment and four times during 14 years of follow-up. A value of <70% of the upper limit of the normal range identified impaired renal function. RESULTS: Twenty-five patients displayed long-term impaired renal function, 23 of them from the RAD or CHEM group. In the RAD group, renal function decreased by 8%, whereas a 14% reduction of renal function was observed in the CHEM group. In the CHEM group the cumulative dose of cisplatin, and in the RAD group the age at treatment, were associated with impairment of renal function. Combining all patients, age at treatment and the type of treatment were associated with impaired renal function. CONCLUSIONS: In 20-30% of the patients with germ-cell tumour, standard radiotherapy and chemotherapy strategies are followed by long-term subclinical impaired renal function. These findings support current intentions to avoid overtreatment with these treatment modalities.

Hormone-resistant prostate cancer with symptomatic pelvic tumours: patient survival and prognostic factors.

OBJECTIVES: To determine the survival and investigate the prognostic significance of immunohistochemical variables and clinical factors in patients with hormone-resistant prostate cancer (HRPC) and symptomatic pelvic tumours, in whom preliminary observations indicated that survival exceeded the median 8-10 months of patients with HRPC and painful bone metastases. PATIENTS AND METHODS: Seventy-five patients with HRPC referred for palliative pelvic radiotherapy between 1980 and 1996 were identified. For all patients at least two prostate biopsies had been obtained, one before primary hormone treatment and at least one after clinical progression despite androgen deprivation (HRPC biopsy). Bone scans at the time of referral were assessed. The medical records were reviewed for clinical variables of possible prognostic significance. Histological grade was recorded, and prostate-specific antigen (PSA), androgen receptors (ARs), Ki-67 and p53 determined immunohistochemically. In 18 HRPC specimens the degree of AR amplification was analysed. RESULTS: Positive staining for ARs was high in the HRPC biopsies, although there was no association with AR amplification. Ki-67 positivity increased after the development of HRPC. The median (range) survival was 14 (1-141) months; age < 65 years was associated with increased survival. In a multivariate analysis the following variables remained independent prognostic factors for survival from the time of the HRPC biopsy: bone metastases (0-10 vs > 10 lesions, P < 0.001), low Ki-67 score (0 vs 1-3, P = 0.006) and low p53 positivity score (0 vs 1-3, P = 0.014) in the HRPC biopsy. CONCLUSIONS: The median survival of patients with HRPC and pelvic tumours requiring palliation seems to exceed that of patients with HRPC and dominating painful bone metastases by at least 4-6 months. Simple clinical (bone metastases) and immunohistochemical variables (Ki-67, p53) enable patients with particularly long survival times to be identified, and in whom palliative treatment needs to be improved.

[Measurement of glomerular filtration rate in connection with 99Tc-DTPA renography]. / Måling av glomerulaer filtrasjonshastighet i tilknytning til renografi med 99mTc-DTPA.

Glomerular filtration rate (GFR) was measured in two groups of cancer patients. In 20 patients, glomerular filtration rate was measured simultaneously with 51Cr-EDTA, 99mTc-DTPA and the X-ray contrast agent iohexol as markers, and with a complete set of eight blood samples during 24 hours. In a second group of 120 patients, we used 99mTc-DTPA only and tested various simplified methods, based on one or two blood samples. Glomerular filtration rate was also calculated from serum creatinine. There was excellent agreement between the values measured with the three markers, and, in the same group of patients, very good agreement with the results of simplified methods. The larger study carried out with 99mTc-DTPA on the second group of patients, confirmed a very good agreement between methods based on the slope of the plasma curve and a method based on one blood sample only. The correlation was worse between the values obtained by any of the radionuclide methods and those calculated from serum creatinine. The latter method should therefore not be used for determination of renal function.

Incidence of radiation-induced insufficiency fractures of the female pelvis: evaluation with MR imaging.

OBJECTIVE: The purpose of this study was to assess the incidence, time of appearance, and evolution of radiation-induced insufficiency fractures of the female pelvis with MR imaging. SUBJECTS AND METHODS: Eighteen women (nine premenopausal and nine postmenopausal) with advanced cervical carcinoma were studied prospectively with MR imaging. The examinations totaled 216 and were scheduled before radiation therapy, three times during radiation therapy, and eight times after radiation therapy. T1-weighted and short inversion time inversion recovery images were obtained. The images were evaluated by two radiologists in consensus. The criterion for fracture was edema, indicated by an area of high signal intensity on short inversion time inversion recovery images and corresponding low signal intensity on T1-weighted images. CT scans (n = 61) and bone scans (n = 58) were used to confirm each diagnosis of fracture. RESULTS: Sixteen (89%) of 18 patients (seven premenopausal and nine postmenopausal) showed findings compatible with insufficiency fractures. Thirteen patients had more than one lesion. The first fracture was detected between 3 and 12 months after the end of radiation therapy. During the study, the fractures associated with edema subsided without treatment in 41 (79%) of 52 lesions in 15 (94%) of 16 patients. Fractures were confirmed with additional imaging in all 16 patients (CT in 14 patients and bone scanning in nine patients). CONCLUSION: Radiation-induced insufficiency fractures were frequently seen in premenopausal and postmenopausal women within 12 months after radiation therapy. Multiple fractures developed within 24 months. Twenty-one percent of the lesions healed during the observation period of 30 months.

Clinical significance of routine pre-cystectomy bone scans in patients with muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the clinical significance of bone scans taken routinely before total cystectomy in patients with bladder cancer of clinical stage > or = T2. PATIENTS AND METHODS: Of 227 consecutive patients with stage > or = T2 bladder cancer diagnosed between 1980 and 1990 but with no clinical suspicion of bone metastases, 91 had a pre-cystectomy bone scan performed at the Norwegian Radium Hospital. The medical records of these patients were reviewed to examine the subsequent development of distant metastases and survival. RESULTS: Of the 91 patients, 37 (41%) developed skeletal bone metastases after cystectomy, unrelated to the clinical T category. In 35 patients, the pre-cystectomy bone scan showed pathological uptake of isotope which was interpreted by the specialist in nuclear medicine as suspicious of (13 patients) or probably caused by (22 patients) skeletal metastases. In either circumstance, the clinician decided that total cystectomy was precluded, particularly as most of the changes could be explained radiologically as being degenerative. In the individual patient, there was no clinically useful correlation between the findings on the pre-cystectomy bone scan and the clinical course of disease, nor if serum alkaline phosphatase (SAP) level was included as an additional predictive factor. However, although not statistically significant, the follow-up of all patients revealed an association between the degree of change on the pre-cystectomy bone scan and the subsequent development of skeletal metastases and cancer-corrected survival. CONCLUSION: Unless further investigations, particularly magnetic resonance imaging (MRI), can be performed, the findings of a routine pre-operative bone scan are usually unable to identify patients with bladder cancer of stage > or = T2 who will not be cured by total cystectomy. An increased level of SAP did not improve the predictive accuracy of a pre-cystectomy bone scan. However, the results indicate that future clinical research should be directed at combining the findings of bone scans and MRI in the search for micrometastases.

[Treatment of chondrosarcoma. A retrospective study at the Norwegian Radium Hospital]. / Behandling av kondrosarkom. En retrospektiv undersøkelse ved Det Norske Radiumhospital.

The authors present a retrospective analysis of 59 chondrosarcoma patients treated at the Norwegian Radium Hospital during the period 1981 to 1993. 31 patients were admitted with untouched tumour, seven after fine needle cytology and 20 after open biopsy or partial excision. One patient had recurrent local disease. Only 20% of the tumours were of high grade malignancy. 51 patients were treated by surgery. Reconstructions were performed in 16 patients, using allografts or endoprostheses. Amputations were performed in six cases and wide excision in 12 cases. In these 18 patients local recurrence appeared in one case, and two developed lung metastases. Only one of the 18 patients operated by amputation or wide excision has since died from chondrosarcoma. Marginal excisions were performed in 26 cases. Nine of these patients developed a local recurrence, five developed metastases and three have died. Six patients had partial excisions. Postoperative radiotherapy was given to one patient only. Five of the six are alive. In one case, the quality of the margins could not be evaluated. A total of 45 of the 51 patients treated for the primary tumour by surgery are alive. The median observation time is four years. Treatment of nonmetastatic chondrosarcoma should be surgical. Chondrosarcoma patients show wider variations in age, localization of tumour and tumour growth rate than patients with other bone sarcomas. Although wide excisions provide the best local control of any grade of malignancy, the mutilation or risk involved may be so great that some patients may benefit from marginal or even partial excision.

Magnetic resonance imaging and 67gallium scan in mediastinal malignant lymphoma: a prospective pilot study.

BACKGROUND: A residual mediastinal mass is common after treatment for bulky mediastinal lymphoma and represents a difficult diagnostic problem. PATIENTS AND METHODS: 19 patients with bulky mediastinal masses due to malignant lymphoma had computed tomography (CT), magnetic resonance imaging (MRI) and 67Gallium scan (67Ga) before treatment, after four cycles of chemotherapy, and two, six and twelve months after end of treatment. RESULTS: MRI and 67Ga showed active tumor in all patients before treatment. Twelve months after treatment full consistency was found between the results of the two techniques. During treatment and the first six months after treatment, the two techniques were not in accord in some patients, partly due to later normalization of MRI compared with 67Ga. CONCLUSION: Both MRI and 67Ga are useful in assessing tumor activity in lymphoma mediastinal masses.

Validity and usefulness of human tumor models established by intratibial cell inoculation in nude rats.

Intratibial injection in nude rats of 1 x 10(6) OHS, MHMX, and LOX human tumor cells resulted in each case in progressively growing bone tumors. When the diameter of the affected leg had increased by 2-3 mm, the animals were examined for uptake of 99mTc-methylenediphosphonate. The OHS osteosarcoma tumors caused sclerotic lesions with high and uniform isotope uptake, and the MHMX unclassified sarcoma showed a mixed pattern with both sclerotic and lytic areas, whereas the LOX melanoma caused lytic bone lesions with low uptake of the radionuclide. These findings were compared with the results of analogous investigations previously performed in the patients from whom the tumor lines originated. Striking similarities in both the morphology and the scintigraphic images were observed between corresponding tumors in rats and humans, with results supporting the clinical relevance of the model systems. When the LOX model was used for therapy experiments, doxorubicin had no effect on the growth of the tibial tumors, which in the control group appeared after a latency of 13.5 days. The alkylating agent mitozolomide increased the median tumor-free latency to 47 days in 7 rats, and 5 animals did not develop tumors within the observation period of 60 days. Doxorubicin was ineffective also against the OHS tumor, whereas ifosfamide and the radionuclide 89Sr-chloride showed significant antitumor activity. The disease-free latency increased from 20 days, in the control animals, to 45 and 28.5 days, respectively, in the 2 treated groups, in which 2 of 7 and 2 of 10 rats were without tumors at 60 days. The data demonstrate that the tibial models discriminated between the action of the different therapeutic agents, and suggest that they may be useful in selecting compounds with clinical activity against skeletal tumors.

Immunoscintigraphy of bone sarcomas--results in 5 patients.

The feasibility of using the murine monoclonal antibody, TP-1, for clinical immunoscintigraphy was examined in a pilot study involving 5 patients with bone sarcomas. 131I-labelled F(ab')2 antibody fragments were injected in doses of 0.8-1.0 mg (90-130 MBq), and the accumulation of radioactivity was examined by scintigraphy, and assessed by direct measurements on biopsied tumour and normal tissue. One osteosarcoma patient had a primary tumour in the femur, whereas the other 4 had single lung metastases detected by other diagnostic methods. Immunoscintigraphy of the femoral primary was optimally visualised after 22 h. In 2 patients, the method failed to detect lung metastasis, in 1 of the cases possibly related to less than optimal methodological conditions. In 2 other patients, increased accumulation of radioactivity indicated one and three lung tumours, in addition to the single metastasis observed by X-ray and CT scanning, tumours that were later confirmed and removed surgically. The concentration of radioactivity in tumour and normal tissues 44-72 h after antibody injection could be measured in 4 patients. The tumour to blood ratios were in the range of 1.2-4.2, compared to 0.1-0.8 for various normal tissues. The results indicate that immunoscintigraphy with TP-1 antibody fragments have a potential for early detection of lung metastases in patients with bone sarcoma.

[Diagnostic aspects of subacute osteomyelitis in children and adolescents. Clinical and radiographic resemblance to primary malignant tumors]. / Diagnostiske aspekter ved subakutt osteomyelitt hos barn og ungdom. Klinisk og røntgenologisk likhet med primaer malign beintumor.

During a six-year period, 17 patients younger than 20 years of age, with a final diagnosis of subacute osteomyelitis, were admitted to the Norwegian Radium Hospital because of an initial suspicion of primary malignant bone tumour. The most common localizations were the metaphyses of long bones (eight patients) and the clavicle (four patients). Pain was the dominating symptom. Common radiological findings were localized osteolysis and/or sclerosis, cortical bone destruction, periosteal reaction and an adjacent, often palpable soft tissue mass. Clinical signs of infection were generally absent, and a positive bacterial culture was obtained from the biopsy material in only one patient. Following extensive investigations, a malignant bone tumour (especially Ewing's sarcoma) remained a differential diagnosis, and open biopsy was indicated in all cases. The patient material illustrates the difficulty in distinguishing between subacute osteomyelitis and malignant bone tumours, and it is stressed that diagnostic investigations for this type of patients should be performed in an oncological centre with experience of bone tumours.

Radiation-induced insufficiency fractures of the sacrum: evaluation with MR imaging.

In patients with malignant pelvic tumors, radiation-induced insufficiency fractures of the sacrum may be mistaken for metastasis. Magnetic resonance (MR) imaging was performed in 18 patients with this condition, and the findings were studied retrospectively. The diagnosis was confirmed with at least one additional imaging modality in 16 patients, whereas the other two patients underwent clinical follow-up at 13 and 20 months without evidence of metastasis. In 17 patients, the lesions were consistent with edema and had diffuse low signal intensity on T1-weighted images and diffuse high signal intensity on short-inversion-time inversion-recovery images, thereby simulating metastasis. In one patient, bilateral sacral wing fractures were demonstrated directly as fairly well-defined linear zones. The alae sacri were involved in all patients; 16 patients had bilateral lesions. Awareness of this clinical entity and of the high sensitivity of MR imaging for demonstrating edema caused by the fracture should prevent confusion with metastatic disease and inappropriate treatment.

Intraperitoneal radioactive phosphorus therapy in ovarian carcinoma. Analysis of 313 patients treated primarily or at second-look laparotomy.

BACKGROUND: Intraperitoneal radioactive phosphorus (phosphorus-32) has been used in ovarian cancer during the last three decades. In the current study, the survival results, the patterns of recurrence, morbidity rates, and phosphorus-32 distribution scintigrams were reviewed in 313 patients treated with phosphorus-32 colloid. METHODS: Between July 1982 and July 1988, 245 patients with epithelial ovarian carcinoma were treated with phosphorus-32 as primary adjuvant treatment; 59 patients received phosphorus-32 as consolidating therapy after negative results during second-look surgery and 9, after positive findings during second-look laparotomy. Fifty patients with negative second-look findings were assigned randomly to receive phosphorus-32 or no treatment. The phosphorus-32 distribution was studied by scintigraphic imaging in 297 patients. RESULTS: The actuarial 5-year crude survival rate was 81% in the group treated with phosphorus-32 adjuvantly and 79% in the group treated after second-look surgery. Crude and disease-free survival rates were similar in both groups randomized at second-look surgery to receive either phosphorus-32 or no treatment. Phosphorus-32 scintigraphy showed major isotopic accumulations in 48 (16%) patients. There were two deaths (0.6%), which, at least partly, could be attributed to the phosphorus-32 treatment. Small bowel obstruction without tumor recurrence occurred in 22 (7%) patients (13 treated surgically and 9 medically) and was not related to any patient characteristic, including phosphorus-32 distribution. CONCLUSIONS: Phosphorus-32 therapy was associated with a considerable number of bowel complications. The occurrence of small bowel obstruction could not be predicted by any patient characteristic. Without an untreated observation group, the authors were unsure whether adjuvant phosphorus-32 treatment conferred a survival advantage.

Does decreased skeletal uptake of 99mTc-methylene bisphosphonate in irradiated bone indicate the absence of bone metastases?

Reduced uptake of 99mTc-methylene bisphosphonate (99mTc-MBP) was found in irradiated bone in all of 13 tumour-free patients who had undergone radiotherapy (30-40 Gy) due to seminoma 3-8 years prior to bone scintigraphy. Decreased uptake of 99mTc phosphate compounds can not per se be interpreted as a sign of absence of metastases or reduced tumour burden.

Distribution of intraperitoneally injected microspheres labeled with the alpha-emitter astatine (211At) compared with phosphorus (32P) and yttrium (90Y) colloids in mice.

The alpha-emitter 211At was bound to polymer microspheres with a diameter of 1.8 microns. The distributions in mice of intraperitoneally injected 211At microspheres, 90Y silicate colloid, and 32P chromic phosphate colloid were compared. The microspheres with 211At spread rapidly in the peritoneal cavity and remained mainly on the intraperitoneal surfaces. Intraperitoneal injection of 90Y colloid resulted in high levels in intraperitoneal fat and the diaphragm, but 1 day after injection 8.5% of the injected dose per gram was found in blood and after 6 days 2.5% was observed in bone. The highest accumulation of 32P was found in liver and spleen. The injection of additional nonradioactive chromic phosphate colloid resulted in an even higher accumulation of 32P in spleen and liver. The same phenomenon was not observed with 211At microspheres. It is suggested that it is not only the particle size which is important in the distribution of intraperitoneally injected colloid, but the amount of colloid, the type of colloid, the addition or presence of other substances such as ascites, and the animal species might also influence the distribution. In conclusion, the intraperitoneal distribution of 211At-labeled microspheres in mice was favorable compared with 90Y and 32P colloid. These data must be viewed cautiously since the distribution might be different in other animal species or humans.