Clinical status and rate of recovery of blood lymphocyte levels after radiotherapy for bladder cancer.

Peripheral blood lymphocytes and leukocyte levels were monitored in 34 patients with bladder carcinoma before, during, and up to 5 years after radiotherapy. Radiotherapy in doses 6500 to 8500 rads caused a marked decline in the numbers of circulating leukocytes and particularly lymphocytes. In patients clinically free of disease for 5 years, lymphocyte counts returned to pretherapy levels within 3 years after radiotherapy. In contrast, in patients with recurrent or residual tumors lymphocyte counts failed to reach pretherapy levels within 3 years after therapy. The rate of recovery from radiation-induced lymphopenia was significantly different for patients who were free of disease as compared to those with recurrent or residual tumor (p less than 0.05). No correlation was found between posttherapy leukocyte levels and clinical status.

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.

Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.

Total parenteral nutrition as an adjuvant to patients undergoing chemotherapy for testicular carcinoma: protection of body composition--a randomized, prospective study.

The efficacy of total parenteral nutrition (TPN) in the protection of body composition, when given as an adjuvant to CVB (cisplatin-vinblastine-bleomycin) treatment to patients with testicular teratocarcinoma, was investigated. Twenty-three patients without previous malnutrition were randomized to receive either TPN or spontaneous oral intake only during their hospital stay, in the course of a total treatment period of 10 weeks. The patients spent weeks 1, 4, 7, and 10 in the hospital to undergo chemotherapy. Energy and nitrogen intakes were profoundly decreased in the spontaneous oral-intake group, whereas the intakes decreased in the TPN group only at home when they relied on oral intake. In spite of the cytotoxic drugs, the TPN group remained in nitrogen balance when undergoing TPN at the hospital. However, they lost substantial body weight and body nitrogen over 10 weeks when compared with the oral-intake group. This loss in body mass was mainly a result of the prolonged anorexia that all the patients had after weekly termination of chemotherapy. This study demonstrates that well-nourished patients can use intravenous nutrition even while receiving cytocidal and cytostatic drug administration. However, intermittent periods of adequate nutrition in the hospital had only a marginal impact, since the positive effects of nutrition were offset by the pronounced anorexia that occurred in all patients outside the hospital for a considerable time after cytostatic treatment.

A method for in vivo analysis of platinum after chemotherapy with cisplatin.

A method to quantify the concentration of platinum in vivo by x-ray fluorescence (XRF) analysis is described. The measurement system consists of a roentgen apparatus, operated at 155 kV and 25 mA, and a high-purity germanium detector. In order to reduce the amount of scattered radiation in the detector the connecting links between the roentgen tube and scatterer, scatterer and patient, patient and detector, are arranged in a three-axial geometry with mutually orthogonal directions. With this system, quantification of platinum can be achieved with a minimum detectable concentration of 8 micrograms/g, for a measuring time of 30 min and an organ depth of 4 cm. The method can be used to follow the uptake and retention of platinum in patients treated with cisplatin, a frequently used cytostatic agent for tumour therapy.

The influence of tumour burden and therapy on cellular cytotoxicity responses in patients with ocular and skin melanoma.

Using a microassay for cellular immunity, tumour specific cytotoxicity was detected in 2/5 cases of ocular melanoma and 1/3 cases of primary cutaneous melanoma before treatment. Reactivity was measured against allogeneic skin melanoma target cells in short or long term in vitro culture. Lymphoid cells from patients with disseminated cutaneous melanoma were either non-reactive (4/8 cases) or gave a nonspecific cytotoxicity on target cells of diverse histogenic origins. Among tumour-free patients tested after surgery, 0/2 patients with ocular tumour were non-reactive 3-4 months post surgery. After sugical excision of cutaneous melanoma 2/2 patients gave tumour specific reactions during the first month after surgery. After longer time intervals, from 5 months to 3 years, only 1/8 patients were reactive. Preoperative radiotherapy in a total skin dose of 10,000 rad produ-ed a transient tumour specific reaction 24 h after therapy in a single case. Following local tumour excision in patients given preoperative irradiation, 2 cases which had previously demonstrated tumour specific CMI lost reactivity. Among 14 tumour-free individuals tested only after preoperative radiotherapy and surgery, at intervals from 5 day to 13 years, a single case gave tumour specific CMI. Palliative irradiation in doses 4000-4960 rad to the inguinal or axillary lymph nodes was found to induce a generalized lymphopenia within 48 h after treatment. Lymphoid cell preparations from patients with localized melanoma contained significantly increased numbers of immature cells (lymphoblasts and myeloblasts) and myeloid precursor elements. Those prepared from patients with disseminated disease had in addition elevated levels of eosinophils but reduced numbers of recoverable lymphocytes.

Fall in blood pressure during radiation therapy.

Blood pressure and heart rate at rest in the supine and standing positions were followed before, during and after irradiation for malignant tumours in 114 patients. A statistically significant gradual reduction in blood pressure during the treatment period was established. This was more marked in older patients and in patients with higher initial blood pressure but was not related to the region irradiated or the type of tumour treated. Particularly if the patient experiences vertigo and nausea on change of position, it seems advisable to check the blood pressure during treatment.

Uptake and retention of platinum in patients undergoing cisplatin therapy.

Results of in vivo measurements of the platinum concentration in kidneys and tumours of patients treated with cisplatin for testicular carcinoma, head and neck tumours and brain tumours are presented. The measurements were performed with an x-ray fluorescence technique. Our earlier studies have shown that maximum platinum levels in kidneys were reached 3-4 h after an intravenous injection of cisplatin. The present study showed that, at that time, the ratio between the concentration of platinum in kidney and in blood serum was 22 +/- 7 (+/- 1 S.D.). Between 24 and 72 h after administration this ratio was 10 +/- 3, as shown in another group of patients. Measurements of platinum concentration in brain tumours showed varying maximum uptake, between 14 and 40 micrograms/g, 5-15 h after administration. There was an indication that radiotherapy may increase the uptake of cisplatin in normal brain tissue. The technique described can be used for further studies of the platinum concentration in tumours and risk organs in connection with cisplatin therapy. Such studies are needed to find out how to improve the therapeutic effects and lower the toxic ones.

Determination of prostate-specific antigen in serum by immunoradiometric assay.

A better understanding is needed of the role of pre-analytical factors if prostate-specific antigen (PSA) is to be reliably used as a tumor marker. Reports on the analytical performance of TANDEM-R PSA (Hybritech, Inc., San Diego, CA) differ considerably with respect to detection limit and imprecision, differences that might be due (e.g.) to the use of different control matrices, to between-batch variations in reagent composition, or to nonrobustness of the assay. During nine months we determined PSA in 986 serum samples from 728 male urology patients and 54 samples from women (25 assay runs). As controls we used two serum pools with low PSA concentration and two widely used commercial controls. The within-assay CV for patients' samples was similar to that found with the commercial controls: 2.6% to 3.4% in the upper part of the normal reference interval. Precision was worse at lower concentrations (CVs 5-10% at about 0.5 micrograms/L). Imprecision tended to be higher at the end of runs. Assay drift for 100-tube runs was -4%. PSA was stable at -20 degrees C during six months. Neither the polyester polymer in SST tubes nor a hemolysate had any detectable effect on PSA values. Clinical analysis of the first 322 patients and all patients with PSA less than or equal to 0.20 micrograms/L highlighted the requirements for strict adherence to sampling instructions and to stringent quality control also at low analyte concentrations (analyte-free sera and sera with PSA concentrations 0.2-0.5 micrograms/L). Values with TANDEM-R PSA and IRMA-Count PSA (Diagnostic Products Corp., Los Angeles, CA) correlated well with no difference in detection limit or with samples from women. Within-assay precision was better with IRMA-Count PSA in the upper part of the normal reference interval and above. The designs of the two assays were compared in a format that is generally applicable for immunoassay kits (NORDKEM kit group, unpublished), and subjective impressions were recorded.

Ultrastructure, karyology and immunology of a cell line originated from a human transitional-cell carcinoma.

A cell line (J82) was derived from a poorly differentiated, invasive, transitional-cell carcinoma, Stage T3. The cells have been propagated in vitro for 5 years and showed 100% aneuploidy and a mixed epithelial-fibroblastic morphology. The majority of cells contained 2Y chromosomes and several distinctive markers. Peripheral-blood lymphocytes from the donor of the J82 cells were tested sequentially for cytotoxicity toward autologous and allogeneic tumour cells. Autologous cytotoxicity was detected against J82 cells in early in vitro passage. Allogeneic lymphocytes from some patients with transitional-cell carcinoma were also cytotoxic to J82 cells in primary culture. However, selective cytotoxicity by lymphoid cells from bladder-carcinoma patients was not detected against J82 cells in long-term tissue culture.

The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma.

This study has evaluated whether long-term and permanent total parenteral nutrition (TPN) can protect body composition and exercise capacity during iterated courses of chemotherapy (PVB) in men with testicular carcinoma. Thirty-three men were randomly allocated by means of a computer based algorithm to receive either TPN (at hospital and home) during the entire chemotherapy period or to rely on spontaneous oral intake only. Nutrition status was assessed by measurements of whole body nitrogen (neutron activation), total body potassium, body water, urine creatinine excretion, loco-regional body nutrition indexes (AMC, TSF) and biochemical plasma concentrations (albumin, thyroid hormones). Whole body respiratory gas exchanges were measured during resting, submaximal and maximal exercise. TPN was prescribed on an individual basis in all study patients to cover 150% of their measured caloric need; nitrogen was given as 0.2 g N kg-1 day. All individuals were allowed to eat freely throughout the study. TPN patients were in overall positive energy balance (+850 Kcal day-1), while the control group was in negative balance (-532 Kcal day-1). This led to weight gain in the TPN group (+2.2 +/- 1.0 kg) while the control group lost significant weight (-4.2 +/- 1.1 kg). The average spontaneous oral caloric intake was 1014 +/- 153 Kcal day-1 in the TPN group and 1484 +/- 200 Kcal day-1 in the control group; total protein intake corresponded to 1.5 g protein kg day-1 in the TPN group and 0.7 kg day-1 in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective randomized study of preoperative irradiation with cystectomy or cystectomy alone for invasive bladder carcinoma.

Prognosis was studied in 44 patients with urothelial bladder tumors, WHO grades 2 or 3, invading the lamina propria or the muscular coat, without signs of distant metastases. The patients were preoperatively randomized into two groups according to treatment: total cystectomy with or without preoperative irradiation. The 3- and 5-year survival rates were 81 and 61%, respectively, in 22 patients not receiving preoperative irradiation. 22 patients preoperatively irradiated had 3- and 5-year survival rates of 81 and 75%, respectively. Individuals who were tumor-free at cystectomy after preoperative irradiation had an excellent prognosis and tumor eradication was achieved in 80% when a cumulative radiation effect (CRE) above 1,400 reu was administered. Only 1 of 10 patients who received a CRE above 1,400 reu died from bladder tumor. This might indicate that preoperative irradiation improves the survival rate providing the CRE exceeds 1,400 reu. The presence of residual tumor after transurethral resection, aimed at resecting the tumor completely, seems difficult to evaluate since the surgeon was mistaken in believing the excision to be radical in more than 50% of the cases. The risk of error was especially high when the tumor infiltrated the muscular wall of the bladder.

Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA).

During a 5-year period (1981-86) 588 consecutive patients with nonseminatous germ cell tumors of the testis were included into a prospective Swedish-Norwegian multicenter study (SWENOTECA) and clinically staged according to the Royal Marsden system. A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease. Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients. The overall clinical staging accuracy was 75%. All the 40 patients with pathological serum AFP and/or HCG patterns before RPLND had PS2 disease, compared to 81/282 (29%) of patients with normal marker patterns. The PS2 patients with pathological marker patterns had significantly more and larger retroperitoneal metastases than those with normal AFP and HCG values. Elevated pre-orchiectomy AFP level indicated significantly reduced risk of PS2 disease in CS1 patients, but this effect became non-significant if the CS1Mk+ and CS2A cases were included into univariate or multivariate analyses. We suggest that the 'good risk' effect of pre-orchiectomy AFP elevation for CS1 cases may be caused by a selection mechanism during the clinical staging process.

Detection by monoclonal antibody of carbohydrate antigen CA 50 in serum of patients with carcinoma.

A solid phase radioimmunoassay was devised for measuring the value of the carcinoma associated carbohydrate antigen CA 50 in serum based on the use of a specific monoclonal antibody (C 50). Samples of serum from 259 patients with carcinoma, 114 patients with other malignancies or inflammatory diseases, and 150 healthy controls were examined. Serum values of CA 50 exceeding the mean plus three standard deviations for control samples from blood donors were found in a high proportion of patients with colorectal adenocarcinomas (50% of those with early, localised tumours and 75% of advanced cases), other gastrointestinal carcinomas (69%), uterine cancer (75% of those with corporeal and 88% of those with cervical cancer), prostatic cancer (90%), lung cancer (52%), and breast, ovarian, kidney, and urinary bladder carcinoma (26-67%). The CA 50 values in samples from patients with inflammatory diseases, including ulcerative colitis, with rare exceptions (0-7%) were within the normal range, as were those in patients with various sarcomas and malignant melanoma. Measuring serum values of CA 50, which is evidently a generalised carcinoma associated antigen, may be useful in clinical research studies of the diagnosis, management, and prognosis of patients with different types of carcinoma.