Search PubMed⌕ Search

Biomedical subjects

L R Holsti

Publications and source records attributed to L R Holsti.

At least 37 records · Page 2Linked to original sources
PubMed1991

Procollagen-III in serum, plasminogen activation and fibronectin in bronchoalveolar lavage fluid during and following irradiation of human lung.

In the search for predictors of late radiation-induced lung injury we studied procollagen type III peptide concentration (P-III-P) in serum as well as fibronectin and plasminogen activation in bronchoalveolar lavage (BAL) fluid during and following irradiation of human lung. The patients received either high-dose hemithorax irradiation for pleural mesothelioma (11 patients) or high-dose irradiation with individually shaped fields for non-small cell lung cancer (12 patients). The severity of radiation fibrosis was assessed clinically from CT scans 6 months and 12 months after treatment. Four scores were used: severe, moderate, mild, or normal. Radiological lung injury varied from "severe" (9 patients) to near absence of injury-"normal" (6 patients). Serum levels of P-III-P, when measured weekly during the 5-week period of radiotherapy or at several time-points after treatment, did not show consistent changes, nor did the levels correlate with the score for radiation fibrosis as assessed by CT scanning. Changes in fibronectin levels or in markers of plasminogen activation in BAL fluid did not correlate with the development of late lung injury. The levels of BAL fluid plasmin and plasminogen activator as assessed zymographically, but not the free net enzyme values, showed a tendency to be elevated in patients with severe radiation-induced lung injury, suggesting a possible role for inhibitors of the plasminogen activation cascade in the process of radiation-induced lung injury.

Adult↗
PubMed1991

The effect of fractionated irradiation on cell kinetics.

The effects of single and split-dose irradiation were compared by in vitro experiments on HeLa cells. Changes in rate of cell proliferation were detected by flow cytometry, simultaneously determining the DNA content and the bromodeoxyuridine incorporation of individual cells. Cell cultures were irradiated with either a single dose of 1-6 Gy or with a corresponding dose divided into multiple fractions given at 1-6-h intervals. A dose-dependent accumulation of cells in G2/M phase was observed. The method was sensitive enough for the detection of G2/M block even after 1 Gy. The block disappeared completely within a 24-h follow-up time at dose levels up to 3 Gy. Interestingly, no differences in cell kinetics were observed between the single and split-dose regiments. This approach proves to be valuable in evaluating novel fractionation models and the effects of radiation on the cell kinetics of human tumor cells.

Cell Division↗
PubMed1991

Radiographic chest assessment of lung injury following hemithorax irradiation for pleural mesothelioma.

To characterize the nature, extent and time-course of radiation-induced lung injury, and to evaluate the usefulness of serial chest radiographs in this assessment, we studied 253 chest radiographs of 46 patients with pleural mesothelioma given hemithorax irradiation according to one of four different regimens: I 20 Gy; II 55 Gy; III hyperfractionation 70 Gy; IV hyperfractionation 35 Gy followed by local hypofractionation 36 Gy. Lung injury on the chest radiograph was graded from 0 (none) to V (maximal) based on the degree of loss of aerated lung tissue. Grade I changes were present 1-2 mths after radiotherapy in regimens II-IV. Grade V injury had developed in all but 3 out of 4 patients of the 20 Gy group by 6-12 months after irradiation. The extent and time-course of radiation-induced lung injury could be defined by serial chest radiographs alone. However, the documentation of tumour status and/or infections needed additional imaging or laboratory investigation, especially when grade IV-V lung injury was present. For research protocols evaluating radiation-induced lung injury serial chest X-rays are recommended at the following time-points: before treatment and 2, 6 and 12 mths after treatment, with additional computerized tomographic (CT) scans as required for differential diagnosis.

Female↗
PubMed1990

Treatment of advanced breast cancer with 20 mg toremifene, a phase II study. Preliminary communication.

Fourteen postmenopausal women with estrogen-receptor positive advanced breast cancer and no prior cytostatic treatment received 20 mg toremifene daily as a single dose after a loading dose (120----60----60 mg) for the first 3 days. All were evaluable and had undergone at least 6 weeks' treatment. Results were: no complete remissions (CR), 3 partial remissions (PR), 8 no change (NC) and 3 cases of progressive disease (PD). Three patients had mild side effects: nausea, insomnia, sweating and arm pain.

Aged↗
PubMed1990

Safety and efficacy of toremifene in breast cancer patients. A phase II study.

46 postmenopausal women with estrogen receptor positive breast cancer entered a phase II study with a novel antiestrogen, toremifene. Patients had either recurrent or primarily inoperable advanced disease. No prior or concurrent cytostatic or hormonal treatment was allowed. Eight patients (17%) achieved complete response (CR), 17 (37%) partial response (PR) and 13 (28%) had stabilization of their disease at least for three months. The mean durations of responses were 52 +, 53 + and 27 + weeks, respectively, with 5 patients in CR, 6 in PR and 1 with no change (NC) still continuing the treatment. No significant differences could be seen in response rates according to the concentration of estrogen receptors or presence of progesteron receptors in this group of patients. Toxicity was not a problem, in general, the treatment was well tolerated. Two side effects (sweating and vertigo) were classified as severe and one patient after achieving PR interrupted the treatment because of tremor.

Aged↗
PubMed1990

Natural interferon-alpha alone and in combination with conventional therapies in non-small cell lung cancer. A pilot study.

Fourteen previously untreated patients with non-small cell lung cancer (NSCLC) were treated with natural interferon-alpha (IFN) in combination with conventional therapies. The planned dose of IFN was 6 x 10(6) IU/d.i.m. 5 days a week for 12 weeks. After 12 weeks of IFN monotherapy patients with M0 disease underwent twice-daily fractionated radiotherapy (RT), 55 Gy/4F/30 d, while IFN continued. Patients with M1 disease received 3 cycles of chemotherapy (CT) concomittantly with IFN. CT consisted of cisplatinum (P) 90 mg/m2 i.v. on days 1, 28, and 56 and of vindesine (VDS) 3 mg/m2 i.v. once a week 5 times and every other week thereafter for up to 8 courses. Thirteen patients were evaluable for response and toxicity. There were 9 patients with epidermoid, 3 with adeno- and one with large cell carcinoma. In 12 of 13 patients, the disease remained stable for 1 month during IFN monotherapy and one acheived a minimal response, which lasted 4 weeks. Of seven patients who completed the 12-week course of IFN monotherapy, 4 achieved stable disease (SD) and 3 had progressive disease. Three patients received RT and one received CT in combination with IFN as their subsequent treatment. There were 3 partial responses (2/3 after RT + IFN, 1/1 after CT + IFN), and 1 SD. Fatigue and weight loss were the most severe side-effects during IFN monotherapy. The combination of IFNs with conventional therapies might be clinically useful. We recommend further testing in larger studies.

Aged↗
PubMed1989

A comparison of cis-platinum-vindesine and cis-platinum-etoposide combined with radiotherapy for previously untreated localized inoperable non-small cell lung cancer.

Seventy-two previously untreated patients with localized inoperable non-small cell lung cancer were randomized to a study comparing the efficacy of cis-platinum-vindesine (P-VDS) and of cis-platinum-VP16 (P-VP16), both combined with split-course radiotherapy. Fifty-nine patients were evaluable for response after the minimum requirement of two chemotherapy cycles. Both arms were further randomized to two split intervals, 3 or 5 weeks. The response rate to chemotherapy only (three cycles) was 66% for P-VDS and 50% for P-VP16. Radiotherapy increased the response rates to 83 and 67%, respectively. A Karnofsky score of 80% or more and the 3-week split interval were significant positive prognostic factors. Of all patients, 66% had local or combined recurrences and 17% relapsed at a distant site only. Since the 2-year survival rates are not strikingly better than those obtained by radiotherapy alone, we feel that these regimens should be restricted to further investigations of the role of chemotherapy in the treatment of different clinical presentations of NSCLC.

Aged↗
PubMed1988

Inoperable non-small cell lung cancer: radiation with or without chemotherapy.

We report a randomized multicentre study of split-course radiotherapy (RT), with or without combination chemotherapy (CT), in 238 patients with inoperable non-small cell lung cancer (NSCLC), previously untreated, confined to one hemithorax and the mediastinal nodes. In both treatment groups RT consisted of 55 Gy in 20 F given over 7 weeks with a 3-week rest interval. CT consisted of the 3-drug regimen CAP: C = cyclophosphamide 400 mg/m2, A = adriamycin 40 mg/m2, P = cisplatin 40 mg/m2; 2 cycles of CAP given before RT, one during the rest interval and six after RT. Seventy per cent in the RT arm and 67% in the RT-CT arm had epidermoid carcinoma. No significant difference was apparent between the RT and the RT-CT arms with respect to objective response rates (CR + PR) (44 and 49%, respectively), median duration of response (278 and 320 days), local failure (31 and 20%), distant progression (23 and 20%) or median survival (311 and 322 days). The survival figures showed an almost significant (P = 0.05) therapeutic advantage of the combined regimen with stage IIIM0 disease. Progressive disease was the cause of death in 92% and 88%. We conclude that chemotherapy did not contribute significantly to either local control or survival as compared to radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Split-course versus continuous radiotherapy. Analysis of a randomized trial from 1964 to 1967.

A randomized clinical trial was performed from 1964 to 1967 to compare the therapeutic results of split-course external beam radiotherapy with those of continuously fractionated treatment. Altogether 439 consecutive patients with carcinoma of larynx, nasopharynx, hypopharynx, oropharynx, oral cavity, oesophagus and urinary bladder were included in the series. 227 patients received split-course treatment and 212 were treated by the continuous-course method. In the split-course treatment there was a 2-3 weeks' interruption after 25-30 Gy. This break was compensated by a 10% increase in the total dose. For each tumour site local control and failure rates for the 2 treatment techniques were similar. No significant differences in 5- and 10-year survival were noted. Acute side effects were milder in all patients treated with split-course. The occurrence of late reactions was similar in both treatment groups. However, severe late reactions in the urinary bladder were somewhat more frequent in patients treated with split-course technique; the difference was not statistically significant. We conclude that there were no significant differences in local control, long-term survival and late normal tissue reactions between the treatment groups. The acute normal tissue reactions were milder in the split-course treated groups. We still regard split-course as a useful treatment modality provided the interruption is compensated with about 10% increase in total dose. However, more studies are needed to show which tumours proliferate during prolonged radiotherapy.

Cell Division↗
PubMed1988

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Adult↗
PubMed1987

Enhancement of radiation effects by alpha interferon in the treatment of small cell carcinoma of the lung.

The effects on lung tissue and tumor of natural human alpha interferon (IFN) and radiotherapy were investigated in a multimodality treatment program for selected patients with small cell carcinoma of the lung (SCLC). Interferon was given first as a single agent, then concomitantly with radiotherapy to 12 previously untreated patients with limited disease. At disease progression outside the chest, interferon was discontinued and combination chemotherapy was initiated. In the first series, 7 patients received a high interferon induction dose (800 X 10(6) IU i.v. over 5 days) followed by low-dose maintenance therapy (6 X 10(6) IU i.m. TIW), median total dose 1380 X 10(6) IU (range 794-2074). At local progression, split-course radiotherapy, 55 Gy/20 F/7 wk, was added to interferon therapy. In the second series, 5 patients received low-dose interferon from the start (6 X 10(6) IU i.m. daily) combined with twice-a-day fractionated radiotherapy 44 Gy/40 F/4 wk. Median total dose of interferon in this series was 698 X 10(6) IU (range 354-828). Tumor response and normal tissue reactions were evaluated by monthly chest X rays, 3-monthly CT scans, restaging bronchoscopies and by serial respiratory function tests. Autopsy specimens from both lungs within and outside the radiation field were systematically evaluated when available. After the completion of radiotherapy, there were 4/7 CR in the high-dose IFN group compared to 3/5 CR in the low-dose IFN group. Rapid shrinkage of huge tumor masses was observed. At 2 months post radiotherapy radiological grade III fibrosis occurred in 4/7 patients in the high-dose and 1/5 patients in the low-dose group. Lung function studies showed a significant decrease in diffusing capacity and in lung volumes. Seven patients died within 12 months from start of interferon treatment, one of them from treatment complication. At autopsy the tumor area was in most cases replaced by severe fibrosis. Outside the radiation field lung fibrosis was mild. Our results suggest enhancement of radiation effect by interferon with a possible dose and/or schedule dependence of interferon and radiotherapy and call for more clinical studies of IFN and radiotherapy in combination.

Carcinoma, Small Cell↗
PubMed1987

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)

Adult↗
PubMed1987

Radiation pneumonitis and fibrosis following split-course radiation therapy for lung cancer. A radiologic and physiologic study.

Radiographic signs of radiation pneumonitis and fibrosis were assessed and pulmonary function monitored in lung cancer patients after two different split-course radiation therapy schedules, one with a rest interval of 3 weeks and the other with a rest interval of 5 weeks, the total radiation dose being the same in both treatments (55 Gy/20 fractions/7 or 9 weeks). Post-mortem findings were analysed when available. Spirometric measurement of vital capacity, determination of diffusing capacity for carbon monoxide (DL) and alveolar volume with the single breath technique, and determination of regional distribution of lung perfusion by two different techniques, radiospirometry and gamma camera digital display following intravenous injection of 133Xe, were carried out before and at various times after the completion of irradiation. Of the physiologic parameters, only DL showed a significant decrease 6 as well as 9 months post-treatment (p less than 0.05). No difference between the two treatment schedules could be shown with regard to grade or time pattern of radiologic changes or decrease in DL. The findings suggest that measurement of DL may be of value in monitoring patients included in research protocols for radiation therapy of lung cancer as well as in selection of patients for this treatment.

Aged↗
PubMed1985

Human leukocyte interferon as part of a combined treatment for previously untreated small cell lung cancer.

Human leukocyte interferon, HuIFN-alpha (LE), has been tested in combination with radiotherapy and chemotherapy for previously untreated small cell lung cancer. Nine patients with limited disease received high-dose IFN followed by a low-dose regimen; and six patients had a low-dose regimen from the beginning. The high dosage of IFN consisted of 800 X 10(6) IU given as a continuous intravenous infusion for 5 days, followed by 6 X 10(6) IU i.m. three times weekly. If the first site of disease progression was local or in a central nervous system location, radiotherapy (55 Gy/20 F/7 weeks locally and/or 30 Gy/10 F/2 weeks whole brain) was applied and IFN was continued. Chemotherapy was administered only if there was disease dissemination outside the chest. Three patients achieved minor response for as long as 20, 25, and 42 weeks, respectively, with IFN alone. Three of five complete responders to IFN-radiotherapy died 18, 33, and 41 weeks from the start of IFN treatment without chemotherapy. Autopsy did not reveal macroscopic or microscopic tumor at any site, but there was severe radiation pneumonitis. Four of nine patients were administered chemotherapy subsequent to IFN-radiotherapy because of disease dissemination. The median length of survival of the entire group was 41 weeks. On the low-dose regimen, one patient achieved partial response with IFN alone (duration, 12 weeks); of five evaluable patients three achieved complete remission and two partial remission to IFN-radiotherapy, and one of the three complete responders to IFN-radiotherapy died of severe radiation pneumonitis at 21 weeks from the start of IFN treatment. No tumor was detected at autopsy. The study is in progress. Average survival at present is 33 weeks. The results derived from both our studies suggest a growth-delaying effect of HuIFN-alpha (Le) on small cell lung cancer. They also suggest potentiation of radiation by HuIFN-alpha (Le). Memory and psychomotor dysfunction, fatigue, and anorexia were dose limiting with both short-duration, high-dose and long-duration, low-dose IFN therapy. We feel that IFN, as part of a combined multimodality treatment of small cell lung cancer, may play a role by delaying metastatic dissemination.

Adult↗
PubMed1983

Hair transplantation in alopecia due to radiation.

Two cases of alopecia due to radiation of the scalp are presented in which it has been possible to achieve a technically and cosmetically satisfactory reconstruction by punch hair grafting. This does not mean that every case is suitable, but it does mean that those without contraindications should at least be given a try.

Adult↗