Sakari Mustakallio--pioneer in cancer research: a Finnish pioneer in cancer education, medical radiology and radiotherapy.
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Breast Neoplasms↗
Biomedical subjects
L R Holsti
Publications and source records attributed to L R Holsti.
Biweekly dose escalation in curative accelerated hyperfractionation for advanced head and neck cancer: a feasibility study.
PURPOSE: To study the feasibility of a dose-escalated accelerated hyperfractionation schedule for patients with advanced head and neck cancer. MATERIALS AND METHODS: Twenty-nine previously untreated patients with advanced squamous cell carcinoma were treated with the following biweekly dose-escalated accelerated hyperfraction schedule: during the first 2 weeks 1.2 Gy twice a daily (bid) up to 24 Gy, thereafter during the next following 2 weeks 1.4 Gy bid to 28 Gy in 20 fractions, and thereafter 22.4 Gy in 1.6 Gy bid fractions during 1 1/2 weeks. Thus, the the total dose was 74.4 Gy in 54 fractions given in 5 1/2 weeks. RESULTS: The planned total dose was given within the planned time to 19 (66%) patients. For seven patients the treatment time was prolonged with 1 to 6 days because of department closure for holidays or machine-down days, and in three cases the treatment time was prolonged more than 8 weeks. When the tumor responses were evaluated at 3 months after given radiotherapy, 27 (93%) patients showed complete tumor clearance, 1 patient had a recidual focus, and 1 patient showed progressive disease. The ultimate 1-, 2-, and 3-year local control rates were: 87, 71, and 60%. Four patients had a salvage laryngectomy. The 1-, 2-, and 3-year survival rates for all patients were as follows: 96, 81, and 73%. All patients developed confluent mucositis, 15 patients were hospitalized for nutritional support, and 11 patients had moist desquamation. However, all acute reactions healed completely, and no serious late complications were observed. CONCLUSIONS: This is a safe and effective treatment schedule for patients with advanced head and neck cancer.
Adult↗
Altered fractionation of hemithorax irradiation for pleural mesothelioma and failure patterns after treatment.
Malignant pleural mesothelioma is a rare malignancy with a bleak prognosis. The role of radiotherapy has not yet been clarified. Our aim was to study the effect of altered fractionation on mesothelioma. We have treated 57 patients, 41 males and 16 females, with hemithorax irradiation with six different fractionation schedules. All the patients have been included in a combined modality program consisting of surgery followed by chemotherapy and finally by hemithorax irradiation. The radiotherapy schedules used were: I. Conventional fractionation of 20 Gy in 10 fractions over 12 days. II. Split-course radiotherapy 55 Gy in 25 fractions of 2.2 Gy over 7 weeks (a two weeks rest halfways) followed by a boost dose of 15 Gy over 8 days to the major tumour area. III. Hyperfractionation of 70 Gy over 7 weeks, 1.25 Gy BID with a 6-h interval and a 10-day rest halfways. IV. Combined hyperfractionation and hypofractionation, 35 Gy hyperfractionation in 28 fractions (1.25 Gy BID with a 6-h interval) over three weeks followed by 36 Gy hypofractionation 9 fractions of 4 Gy given every other day over 3 weeks to the major tumour areas only. V. Hypofractionation of 38.5 Gy over 15 days (9 x 3.5 Gy). VI. Combined conventional radiotherapy and hypofractionation with 20 Gy given conventionally in 10 fractions followed by 10 fractions of 3 Gy over two weeks, overall time 4 weeks. The 2-year survival rate of all patients was 21% and the 5-year survival rate 9%. Two patients are still alive more than 6 and 9 years after radiotherapy. Progression occurred after surgery in four patients, during and after chemotherapy in 22 patients and after completed radiotherapy in 29 patients. The pattern of progression was similar in each treatment group.
Adult↗
How radiation oncology emerged as a discipline in Finland.
The news about the discovery of Röntgen's new rays spread over Finland quite early, and the first Finnish writing about the rays appeared in February 1896. The first x-ray machine was installed in 1897. Proper training of radiologists began, however, at a comparatively late date. For a long time the position of radiologists remained a subordinate one. Radiology had the nature of a spare time hobby, because in most hospitals surgeons treated x-ray machines as a sideline. Because of this, scientific research work was delayed. The specialty of x-ray diagnosis and therapy was, however, established in 1921, and the Finnish Society of Radiology was founded in 1924. The first radiotherapy department with its own beds was opened in 1936 in Helsinki. In 1950, the first professor of medical radiology was appointed at the University of Helsinki. The Finnish Cancer Society played an important role in developing the radiotherapy net in the country by supplying cobalt devises and auxiliary hospital activities in the 1960s. In the early 1960s roentgen diagnosis and radiotherapy were separated into two distinct disciplines. There are now five medical faculties with chairs in radiation oncology. The country is divided into five regions for cancer care. The managing groups in each region are headed by the professor of radiotherapy and oncology. The radiation oncologists in Finland are involved in diagnosis and staging of cancer and are responsible for radiation therapy, chemotherapy and hormones. They are responsible for follow-up of treated patients, their own wards, and the general care of their patients.
Finland↗
[The era of 100 years radiotherapy].
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Finland↗
Development of clinical radiotherapy since 1896.
From the discovery of x-rays in November 1895 and the first publication in December 1985 it did not take long for the first x-ray therapy of cancer in January 1896. The first 25 years in the history of radiotherapy was not a very flattering period for the discipline. During the following 25 years, however, important developments in clinical radiotherapy occurred and in some countries the speciality of radiotherapy was established in the 1930s. In the last 50 years gradual changes have taken place and now modern radiotherapy is an established curative method in the treatment of cancer. The scientific background of radiotherapy is solid, and the understanding of cancer biology and radiobiology has improved drastically. The radiotherapists of today are cancer specialists, oncologists. The technical development has been enormous. The future of radiation oncology looks very promising, with local cancer treatment being shown to be most effective.
Europe↗
Effect of split-course radiotherapy on survival and local control in advanced localized prostatic carcinoma.
PURPOSE: to analyze the effect of overall treatment time of radiotherapy on survival and local control in locally advanced prostatic cancer in a split-course treatment setting. METHODS AND MATERIALS: 168 patients with Stage C prostatic cancer treated during 1979-1989 by the split-course method where the overall treatment time is protracted. Treatment consisted of whole pelvis irradiation of 40 Gy in 4 weeks, followed by a planned 3-week interruption and an additional 26 Gy by the reduced field technique to a total dose of 66 Gy in 9 weeks and 30-33 fractions. The overall treatment time varied from 55 to 100 days. Thirty-eight percent (63) of the patients were treated primarily with radiotherapy, while the rest (105) had received androgen ablative therapy during 2 to 4.5 years before radiotherapy. To examine the effect of treatment time on local control, the patients were divided into three groups ( < or = 63 days, 64-70 days, and > 70 days) by treatment time. RESULTS: the 5-year actuarial survival rates, calculated from the date of diagnosis, were 91% for the hormonally manipulated patients and 69% for the patients treated with radiotherapy alone. The 5-year actuarial local control rates, counted from the start of radiotherapy, were 84% for radiotherapy and 80% for the hormonally manipulated group. Overall, no significant effect of treatment time could be seen, either for radiotherapy alone or for the hormonally manipulated group. The results were similar when the material was further divided by T category and histologic grade. CONCLUSIONS: no significant effect of overall treatment time (55 to 100 days) on survival or local control was found in either group. The survival time from diagnosis was longer in the hormonally pretreated group. Apparently, with adequate doses ( > or = 65 Gy) the overall treatment time becomes less important for local control of advanced prostatic cancer, even in a split-course treatment setting.
Adenocarcinoma↗
Radical surgery and postoperative split-course radiotherapy in squamous cell carcinoma of the head and neck--factors influencing local control and survival.
During the period 1970-1989, 256 patients with squamous cell carcinoma of the head and neck were treated with radical surgery and postoperative split-course radiotherapy. The 3-week rest period was compensated by a 10% increase in the total radiation dose to 66 Gy. The 5-year actuarial local control rate was 66% in tonsillar, 60% in mobile tongue, 64% in floor of the mouth, 51% in lower gingiva, 63% in laryngeal, and 35% in hypopharyngeal cancer. Failures were observed in 102 patients (40%) and 51 (20%) died of intercurrent diseases. Except in mobile tongue cancer, the results in the logistic regression analyses showed that T- and N-category and pretreatment Karnofsky index had the strongest association with local control, whereas in Cox's proportional hazard's regression analyses T-category and pretreatment Karnofsky had the strongest association with survival. In mobile tongue cancer, the histologic grade and the time interval between surgery and radiotherapy had the strongest association with local control and survival respectively. However, the lengthening of the time interval was often caused by factors or events which could have influenced the prognosis. On the basis of both univariate and multivariate analyses, when the tumour resection margins were free, a time interval of less than 3 months, the overall treatment time and the duration of the split of radiotherapy, became less important for local control and survival when doses of 65 Gy were given by fraction of 2 Gy or greater.
Adolescent↗
[Postoperative irradiation of head and neck carcinomas and prognosticators].
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Combined Modality Therapy↗
N-acetylcysteine in combination with radiotherapy in the treatment of non-small cell lung cancer: a feasibility study.
N-Acetylcysteine (NAC) is a free radical scavenger and could therefore act as a radioprotector. To test the feasibility of administering NAC in combination with radiotherapy, we studied 10 patients with inoperable non-small cell lung cancer who were receiving hyperfractionated radiotherapy (RT) of 1.25 Gy B.I.D. (6-h interval) up to a total dose of 60 Gy/48 fractions/32 days. They were given NAC concomitantly with RT: 100 mg/kg i.v. 30 min before the first RT session followed by 30 mg/kg as an i.v. infusion over 7 h; and 600 mg inhaled 30 min before and after each RT session. The patients were assessed by serial CT scans and lung function studies during a 1-year follow-up period. The treatment regime was feasible, but expensive in time and resources. Normal tissue reactions and tumour responses were similar to those in a control group.
Acetylcysteine↗
Natural alpha-interferon in combination with hyperfractionated radiotherapy in the treatment of non-small cell lung cancer.
Our previous study in patients with small-cell lung cancer indicated that natural alpha interferon might be a radiosensitiser. In this study we considered 20 patients with inoperable non-small cell lung cancer, who were randomly assigned to receive either hyperfractionation radiotherapy alone, 1.25 Gy twice a day (6 hr interval), 60 Gy/48F/32d; or the same radiotherapy concurrently with alpha interferon. Patients in the radiotherapy+alpha interferon arm received 3 x 10(6) IU natural alpha interferon intramuscularly and 1.5 x 10(6) IU inhaled via a dosimeter-equipped jet nebulizer 30 min before each radiotherapy session. Tumor response and radiation-induced lung injury were assessed by serial chest radiographs, computerized tomography scans and lung function studies, during a 1 year follow-up period. No patient in either arm achieved complete response. On the other hand, five patients in the radiotherapy arm and six in the radiotherapy+interferon arm experienced partial response, and the corresponding figures for stable disease were three and one. Combined treatment with radiotherapy and inhaled and intramuscular interferon proved feasible but laborious, for both patients and staff. Pneumonitis and/or oesophagitis in the radiotherapy+interferon arm were moderate to severe, and only two patients tolerated the treatment without any modifications. No treatment modifications were necessary in the radiotherapy arm. The early deaths in the radiotherapy+interferon arm may have been treatment-related. The optimal way to combine interferon and radiotherapy to further evaluate its role as a radiosensitiser needs further studies in larger series.
Adenocarcinoma↗
Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation.
The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.
Adult↗
Natural interferon alfa as maintenance therapy for small cell lung cancer.
We performed a 3-armed phase III study between 1982 and 1990 to evaluate low dose natural interferon alfa (nIFN-alpha) as a maintenance therapy in small cell lung cancer (SCLC) following induction chemotherapy (CT) and consolidation radiotherapy (RT). All patients received four cycles of CT (cyclophosphamide, vincristine, etoposide), followed by split-course RT (55 Gy in 20 fractions over 7 weeks). 410 patients entered the study. 237 patients who completed induction CT + RT and were classified as responders (complete response + partial response) were randomly assigned to arm 1: low dose nIFN-alpha (91 patients); arm 2: maintenance CT, six cycles of CAP (cyclophosphamide, doxorubicin, cisplatin) (59 patients); or arm 3: control arm (no maintenance treatment) (87 patients). Halfway through the study the CAP arm was discontinued. There was no difference in median survival between the groups (IFN: 11 months, CAP: 11 months, control: 10 months), but a clear difference in long-term survival and in survival in the limited disease group, favouring nIFN-alpha maintenance therapy. Proportional hazards regression analysis also showed a significant effect of IFN treatment on survival. Our results suggest a role for nIFN-alpha in maintaining a clinically disease-free status achieved with other treatment modalities.
Aged↗
Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients.
This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma.
Adult↗
Disease stabilization by leukocyte alpha interferon and survival of patients with metastatic melanoma.
Thirty-one patients, 13 males and 18 females, with metastatic malignant melanoma were treated with human leukocyte interferon (IFN) alpha. The dose was 3 x 10(6) IU daily s.c. for 6 weeks followed by 6 x 10(6) IU/day 3 times a week. Only 1 patient (3%) achieved a partial response (PR) while 14 patients (45%) had disease stabilization for 2-8 months. Three patients experienced mixed responses, where some of the metastases responded, while the others were only stabilized. Interestingly, 1 patient showed regression of lung and disappearance of liver metastases after termination of IFN treatment. Two female patients are still alive without evidence of disease. After IFN they were treated with radiotherapy or surgery. The median survival for all the patients was 48 weeks. Our conclusion is that in IFN therapy long-term follow-up is indicated even in the absence of objective responses. In spite of poor response rate IFN may contribute beneficially to survival in a proportion of patients.
Adult↗
Postoperative radiotherapy of squamous cell carcinoma of the tonsil. Factors influencing survival and time to recurrence.
From 1970 to 1988, 40 patients with squamous cell carcinoma of the tonsillar region were treated with surgery and postoperative split-course radiotherapy. The 5-year survival rate for all the patients was 52.5%; the corresponding figure was 100% in stage I, 75% in stage II, 63% in stage III and 15% in stage IV. The local control rate was 100% in stage I, 89% in stage II, 87% in stage III and 38% in stage IV. In the proportional hazards regression analysis T- and N-category and pretreatment Karnofsky index had the strongest association to survival, whereas T- and N-category and total radiation dose were most strongly associated to time to recurrence.
Carcinoma, Squamous Cell↗
Radical surgery and postoperative split-course radiotherapy in squamous cell carcinoma of the mobile tongue: factors influencing local control and the time to recurrence.
During 1981-1988 63 patients with squamous cell carcinoma of the oral tongue (27 females and 36 males) were treated with radical surgery and postoperative split-course radiotherapy. The 3-week rest period was compensated with a 10% increase in the total radiation dose to 66 Gy. The local control rate was 76% in stage I, 71% in stage II, 45% in stage III and 0% in stage IV. Failures were observed in 25 (40%) patients, and 8 patients died of intercurrent diseases. For further analysis the material was stratified in three groups according to the time interval between surgery and postoperative radiotherapy: less than 6 weeks, 6-8 weeks and greater than 8 weeks. The local control rate in the three strata were 75, 57 and 44%, and the 5-year actuarial survival 61, 46 and 30%, respectively. In the logistic regression analysis and the proportional hazard's regression analysis the histologic grade of the primary tumour and the time interval between surgery and the start of radiotherapy were the most important factors influencing respectively local control and time to recurrence. However, it appeared that the lengthening of the time interval was often caused by factors or events which directly can influence the prognosis, such as surgical complications, infections and poor general condition. When cases with such special causes for lengthening of the interval were excluded, the effect of the time interval nearly completely disappeared. It would seem that a final evaluation of the effect of the time interval requires a prospective randomized trial. The same may well hold true for reliable evaluation of the influence of overall treatment time.
Carcinoma, Squamous Cell↗
Diploid predominance and prognostic significance of S-phase cells in malignant mesothelioma.
70 histologically verified, malignant mesotheliomas were analysed by flow cytometry for DNA content and S-phase fraction (SPF) of tumour cells. 60% (42/70) were DNA diploid. 18 of the 28 aneuploid tumours were near-diploid with DNA indices of 1.3 or less. SPF could be calculated in 51 cases. SPF was significantly higher in aneuploid (median 16.0%) than in diploid tumours (median 5.6%). DNA ploidy was not a prognostic determinant; survival was the same for both aneuploid and diploid tumours. SPF, however, was significantly correlated (P = 0.039) with prognosis. Patients who had tumours with a low SPF survived almost twice as long as those with a high SPF. Thus malignant mesothelioma has a peculiar DNA ploidy pattern compared with many other solid tumours, with a predominance of diploid or near-diploid type cells. As in many other tumours, SPF may be used as a clinically relevant prognostic indicator.
Adult↗