Effects of bone marrow transplantation on myocardial function in children.

Of 41 pediatric patients currently alive after total body irradiation (TBI) and bone marrow transplantation (BMT), 30 (allogeneic 20, autologous 10) participated in the study. Pre-transplant therapy included high-dose cyclophosphamide (CY) and TBI (n = 12), high-dose CY alone (n = 4), high-dose Ara C and TBI (n = 5), cisplatinum, high-dose melphalan, VP-16 and TBI (n = 9). Acute cardiotoxicity was suggested by a > 15% decrease in the QRS voltage sum of the limb leads in all patients. Late cardiotoxicity was evaluated 0.5-10 years (median 5 years) post-transplant by ECG, chest radiograph, radionuclide cineangiography (RNCA) and echocardiography (ECHO). Six patients had a persistent decrease in the QRS amplitudes. They were all asymptomatic but had abnormal systolic function at the time of the study. BMT patients differed from their controls in the mean values of both the systolic and diastolic indices of myocardial function shown by RNCA and ECHO. Treatment was associated with decreased myocardial contractility. Isovolumic relaxation time and deceleration time were longer in BMT patients than in controls. Myocardial damage seemed to be worst after CY while high-dose Ara C was tolerated best. We conclude that both acute and late cardiotoxicity may occur after BMT, calling for long-term cardiac follow-up.

Vincristine-cyclophosphamide, the classical two-drug regimen for small-cell lung cancer, evaluated in a randomized study with vindesine.

We performed a randomized study from February 1979 to August 1981 in patients with small-cell lung cancer (SCLC) with the aim of defining the potential advantages of replacing vincristine (VCR) with vindesine (VDS), at that time a new semisynthetic vinca alcaloid, in the classical two-drug combination cyclophosphamide (CTX)-VCR. A total of 116 previously untreated patients were admitted to the study. Of 104 patients evaluable for response, 49 had limited disease and 55 extensive disease. Patients received 10 mg/kg CTX i.v. on days 1-4 and either 1 mg VCR i.v. or 2 mg/m2 VDS i.v. on days 1 and 4, and repeatedly every 4 weeks for 12 courses. In addition, the patients with limited disease received split-course radiotherapy (30 Gy/10 F, 3 or 5 weeks rest, 25 Gy/10 F, total treatment time 7 or 9 weeks) to the primary tumor, the mediastinum, and the supraclavicular areas between the second and third cycles of chemotherapy. The response rate to the first two chemotherapy cycles was 47% (4 complete response [CR] and 22 partial response [PR]) to CTX-VCR and 47% (4 CR and 19 PR) to CTX-VDS. Subsequent to radiotherapy the response rate increased to 93% for CTX-VCR and 100% to CTX-VDS, respectively, in the patients with limited disease. Local recurrence and/or progression occurred in 49% of limited disease responders and in 96% of extensive disease responders. In responders with limited disease, the first site of relapse was loco-regional in 25% for the VDS group as opposed to 15% in VCR group. In the patients with extensive disease, the corresponding figures were 62% for the VDS and 50% for the VCR group. Median duration of remission in all patients treated with CTX-VCR was 132 days compared to 203 days in the CTX-VDS group (not significant, NS). Median survival was 338 days for CTX-VCR vs. 342 for CTX-VDS in patients with limited disease, and 214 days for CTX-VCR vs. 312 days for CTX-VDS in extensive disease (NS). One-year survival figures were 47% for CTX-VDS and 35% for CTX-VCR patients. Two-year survivals were 4 and 9%, respectively. Neurotoxicity was the main toxic manifestation in both treatment groups. Severe peripheral neuropathy (grade 4, World Health Organization [WHO]) did not occur with either drug regimen. Treatment was discontinued because of grade 2-3 neuropathy in one patient after 6 cycles of CTX-VCR and in five patients after 1-6 cycles of CTX-VDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Outcome of surgery for oesophageal carcinoma in a low volume centre, with and without preoperative chemoradiotherapy.

AIMS: To critically assess the outcome of surgery for oesophageal carcinoma, with or without neoadjuvant chemoradiotherapy. METHODS: Since April 1998 until August 2002 resectable oesophageal cancer patients referred to us have received multimodal treatment, consisting of two courses of fluorouracil, cisplatin and hydroxyurea and 2 x 20 Gy of radiotherapy followed by surgery. The outcome of this treatment was compared to the outcome of a historical group of oesophageal cancer patients, treated with surgery alone in the time period 1994 to 1998. The patients represent a consecutive series of 20 resectable oesophageal carcinomas, referred to us since 1994. Four patients (20%) were treated for squamocellular carcinoma, 16 (80%) patients for adenocarcinoma. RESULTS: Treatment related toxicity was low and there was no death attributable to the chemoradiotherapy. Postoperative hospital mortality (< 30 days) and morbidity rates were 10% and 50%, respectively. A complete pathological response (T0) occurred in two of the nine patients in the multimodal group (22%). Overall median survival was 11 months. Median survival among patients in the multimodal group was 14 months, as compared with 7 months in the group treated with surgery alone (P = 0.041). CONCLUSIONS: Despite low volume, outcome of surgery for oesophageal carcinoma was acceptable.

Late effects of radiation treatment of tongue and floor-of-mouth cancer on the dentition, saliva secretion, mucous membranes and the lower jaw.

The purpose of this study was to determine retrospectively any changes in the dentition, saliva secretion, mucous membranes and the lower jaw resulting from the radiation treatment given to patients with cancer of the tongue or floor of the mouth. The study covers 29 patients treated at the Department of Radiotherapy and Oncology of Helsinki University Central Hospital between 1972 and 1981. 23 of the patients were treated for cancer of the tongue and the remaining 6 for cancer of the floor of the mouth. The radiation doses ranged from 5300 to 6700 rad. Clinical examination revealed that the number of carious teeth doubled as a result of radiotherapy, while the incidence of cervical lesions increased by a factor of 10, both compared with the controls. About 70% of the patients studied were found to have either moderate or extensive fungal growth. Stimulated saliva secretion had fallen to about 20% and resting saliva secretion to about 30% of the values for the control group. Radiography revealed pathological changes in the mandible in 34% of the patients. Clinically, 2 patients were found to have extra-oral fistulae. In 1 of these, the spontaneously fractured end of the mandible was visible for several cms. 3 of the patients had undergone hemimandibulectomy because of osteoradionecrosis.

The steady-state pharmacokinetics of tamoxifen and its metabolites in breast cancer patients.

The steady-state pharmacokinetics of tamoxifen and its metabolites was studied in sixteen patients with advanced mammary cancer. Patients were randomized to receive tamoxifen given as Tamofen, Leiras, or as Nolvadex, ICI, 20 mg twice daily for 16 weeks in a cross-over study. Plasma and urine samples were analyzed during one dose interval (12 h) after treatment for 8 and 16 weeks. The concentrations of tamoxifen, N-desmethyltamoxifen, N,N-desdimethyltamoxifen, and metabolite Y were determined in plasma and the areas under the plasma level curves were calculated. 4-Hydroxytamoxifen was not found in plasma. In urine samples only tamoxifen and N-desmethyltamoxifen were above the detection limits even though metabolite Y was also analyzed after acid hydrolysis. There were no statistically significant differences in the concentrations of tamoxifen and its metabolites between the two preparations. The results of nonresponders did not differ from those of responders. Liver metastases had no effect on the metabolism of tamoxifen.

Staging laparotomy in Hodgkin's disease.

Fifty-two untreated patients with Hodgkin's disease underwent preoperative clinical assessment and staging laparotomy between 1971 and 1980. The preoperative studies of liver and spleen were of little value in assessing organ involvement with Hodgkin's disease. In eight out of 20 patients with positive lymphangiogram, staging laparotomy confirmed Hodgkin's disease in para-aortic or iliac lymph nodes. Fourteen patients were incorrectly staged by preoperative clinical assessment, eight patients being overstaged and six patients understaged. There were two surgical complications with no mortality. We conclude that surgical staging for Hodgkin's disease is valuable in making an accurate diagnosis and in determining the most effective treatment, but we believe that the patients must be centered in certain hospitals for clinical and pathological staging.

Cystotomy and peroperative irradiation for bladder cancer: long-term results.

The long-term results were investigated in 46 patients of bladder cancer treated by cystotomy and peroperative irradiation. This combination therapy appears to produce grossly comparable long-term survival results with surgery and radiotherapy. There were ten complications during a ten-year period after the treatment. We think that cystotomy and peroperative irradiation could still be used for the treatment of bladder cancer especially when the tumor is not too large, is situated at the base of the bladder, and segmental resection cannot be performed, and the patient wants to spare the bladder function.

Prognosis in carcinoma of the male breast.

A series of 29 cases of carcinoma of the male breast in Finland is reviewed. The purpose was to analyze the long-term results and establish which factors could have influenced the prognosis. The five-year and ten-year survival rates were 44 and 32%, respectively when deaths from all causes were included in the calculations. When only deaths from carcinoma were taken into account, these figures rose to 65 and 47%. The results of treatment agreed well with those reported by other authors. The pre-diagnosis duration of symptoms, invasiveness of carcinoma into the skin, involvement of axillary nodes and pathologic stage of the tumor seemed to have considerable influence on the prognosis in male breast carcinoma.

Lye corrosion carcinoma of the esophagus: a review of 63 cases.

Clinical material and the results of treatment of 63 esophageal lye corrosion carcinoma patients are presented below. The mean age of patients at lye ingestion was 6.2 years; the mean latent time between lye corrosion and esophageal carcinoma was 41 years. The later the lye was ingested the earlier carcinoma of the esophagus appeared. Eighty-four percent of carcinomas(all of which were of histologically squamous cell type) were found to be in the bronchial bifurcation area of the esophagus. Sixty-eight percent of lye corrosion carcinoma patients had been treated with resection or radiotherapy (over 4000 rads). Every tenth patient of whole material had surveved for over seven years. Both surgery and radiotherapy as practiced in our clinics had better survival rates than for previous esophageal carcinoma series.

Liver scanning in short interval autopsy material of cancer patients.

The accuracy of liver scanning, alkaline phosphatase and 5'-nucleotidase in the detection of the hepatic metastases was studied in short interval autopsy material of 243 cancer patients. The highest percentage of correct diagnosis was by 5'-nucleotidase, alkaline phosphatase was the second, and scanning third. The overall accuracy of liver scan was 68 per cent. It was the better the shorter the time interval between scanning and autopsy. The higher percentage of incorrect diagnoses of the scan was related to a larger number of false positives, the causes of which were to be verified only in half of the cases.

Treatment of small cell lung cancer. Two-drug versus four-drug chemotherapy and loco-regional irradiation with or without prophylactic cranial irradiation.

Fifty-five patients with untreated small cell lung cancer were allocated randomly to receive either a standard 2-drug or a 4-drug chemotherapy regimen. The patients were further randomized to receive or not to receive prophylactic cranial irradiation (PCI) 40 Gy/20 fractions/4 weeks. Each patient also received split-course irradiation against the primary tumour (55 Gy/25 fractions/8 weeks), the mediastinum, and the supraclavicular areas. The standard 2-drug regimen consisted of cyclophosphamide 10 mg/kg i.v. days 1-4 and vincristine 1 mg i.v. days 1 + 4; every 4 weeks. The 4-drug regimen comprised cyclophosphamide 10 mg/kg i.v. days 1-3, vincristine 2 mg i.v. day 1 and 1 mg i.v. day 5, methotrexate 30 mg i.v. days 3 and 5, CCNU 80 mg/m2 i.v. day 2; every 7 weeks. The total treatment time for both protocols was 9 to 12 months. Objective response after 2 cycles of chemotherapy was seen in 46% of patients with the 2-drug regimen and in 56% with the 4-drug regimen. Local radiotherapy increased the response rates to 58% and 90% respectively. The median survival time was 12 months with the 2-drug regimen and 14 months with the 4-drug regimen. The 2-year and 3-year survival rates were 11% and 0% in the 2-drug group and 19% and 15% in the 4-drug group respectively. Toxicity was more severe in the 4-drug group with 4 deaths due to myelosuppression. Altogether, 25 patients received PCI. This did not in any subgroup increase median survival significantly but a reduction of relapses in the central nervous system was seen. Median survival was 13 months with versus 10 months without PCI; 2-year survival rates were 15% and 6% respectively. Morbidity due to PCI did not occur. Although no statistically significant survival advantage could be documented, there was obviously a higher rate of complete responses with multidrug therapy, and longer median duration of remission, median survival and maximal survival.

Radiotherapy in emergency treatment of malignant exophthalmos.

18 patients with severe Graves' ophthalmopathy were treated with retrobulbar irradiation. 14/18 (78%) had at least a satisfactory immediate result to the radiotherapy, and every fourth patient had a good late result with normal eyes. A total depth dose of about 4000 cGy, with about 350 cGy daily fraction dose, and a total depth dose of about 2000 cGy, with about 200 cGy daily fraction dose, gave equal immediate and late results according to the exophthalmos. One patient lost her vision and is discussed in detail in the light of the literature.

Response of postmastectomy lymphangiosarcoma to radiotherapy: report of four cases.

We have reported on four previously unpublished cases of postmastectomy lymphangiosarcoma. All of these cases had suffered from a long-lasting lymphedema of the upper extremity. Only one patient had survived over one year. After radiotherapy she lived four years from first lesion of lymphangiosarcoma. She died locally disease-free in spite of two earlier recurrences, which were also treated with radiotherapy. We believe that only in early cases can the radiotherapy give a good palliation in postmastectomy lymphangiosarcoma.

Preoperative radiotherapy of cancer of the larynx.

A series of 128 patients was treated with preoperative radiotherapy, 3000 to 4500 rd, and surgery in 1968 to 1972 at the Radiotherapy Clinic and Otolaryngological Clinic, University Central Hospital, Helsinki. The absolute three-year and five-year survival rates for the total material were 71.1 and 53.2 per cent, respectively. The postoperative complications were two deaths from pneumonia, one of them after aspiration. In addition, 21.3 per cent of the patients had a postoperative fistula. All the fistulae healed spontaneously.

Unconventional fractionation in clinical radiotherapy.

Radiotherapy with decreasing individual tumour doses has been used in treatment of lung metastases and carcinomas. Treatment given with this unconventional schedule is more effective than conventional radiotherapy based upon equal doses and equal intervals. Tumours could be classified into 2 groups according to the shrinkage rate. In the group shrinking more rapidly, tumours totally disappeared in most instances; furthermore in most instances, tumours in this more responsive group could be identified because in the week after the first fraction they had already started to shrink.

Local management in primary breast cancer. Our experience of 331 cases.

The peroperative exploration of axillary content gave wrong result from the stage of axillary nodes in every fourth case compared with the final result of axillary evacuation. There were no locoregional recurrences in stage I-patients irradiated after mastectomy. In postoperatively irradiated stage II-patients there were locoregional recurrences in 2.5% of cases, which was 1/8 of recurrences of patients not irradiated postoperatively.

Late cardiac effects of mediastinal radiotherapy in patients with Hodgkin's disease.

Twenty-eight patients younger than age 40 years, treated for Hodgkin's disease with mediastinal irradiation, were examined no less than 5 years after the irradiation in order to evaluate the frequency of cardiac abnormalities. Twelve patients (43%) had had some pericardial event after radiation: a diagnosed pericarditis, remarkably increased heart volume, or a conspicuous change of cardiac silhouette, suggesting pericardial fluid. On evaluation, 50% of the patients complained of symptoms, and 13 patients had to stop the exercise test on a low level because of chest pain, dyspnea, or general fatigue. In 13 patients some of the following abnormalities in the electrocardiogram (ECG) was found: right bundle branch block (four), first-degree atrioventricular block (four), abnormal P terminal force (five), or a low voltage (two). In ten patients (38%) an increase of the pericardial fluid was seen in the echocardiogram, and in nine patients the right ventricle wall thickness had increased. In two patients a severe coronary artery disease was found. One died suddenly after an acute myocardial infarction (AMI), and the other had a large anterior AMI. Two patients with chronic pericardial fluid underwent partial pericardectomy. Two cases of mild pulmonary valve stenosis, one pulmonary subvalvular stenosis and two aortic valve deformities were discovered. Eight patients went through cardiac catheterization, and in all but one case the pressures were slightly elevated suggesting diminished diastolic compliance. In summary, 19 of 28 patients had some abnormal cardiac findings, but only three of them were serious ones.