Gudrun Svahn-Tapper

Improvements in the radiotherapy of medulloblastoma, 1946–1975

The prognosis in medulloblastoma has often been reported to be gloomy, and five‐year survival rates of approximately 25% are often reported. In recent years, however, some centers have published results that indicate a possible cure rate of 60% or even more. During the years 1946–1975, 50 children received radiotherapy for medulloblastoma at the University Hospital, Lund, Sweden. During this period the target volume had been defined in three different ways, whereas the target‐absorbed dose had not differed. When only the demonstrated tumor was treated, the ten‐year survival rate was 5%. If the spinal subdural space also was included, it rose to 25%, and when the whole subdural space was treated in addition to the demonstrated tumor, the projected ten‐year survival rate was 53%. It is apparent that the target volume in the radiotherapy of medulloblastoma should include not only the demonstrated tumor but also the whole subdural space from the tip of the frontal lobes down to and including the second sacral segment. The size of the target‐absorbed dose to be aimed at is not settled, but should consider not only the cure rate but also the performance status of the survivors. It seems from the present series that an absorbed dose of 45 Gy in not more than 30 fractions over six weeks to the demonstrated tumor and 30 Gy in 20 fractions over four weeks to the subdural space resulted in a fair frequency of tumor healing and minimal side effects. The delivery of this complicated treatment demands a high degree of precision in the technique. In this material the performance status of the children was not affected by the radiation treatment. Cancer 45:670‐678, 1980.

Radiation dose as a risk factor for malignant melanoma following childhood cancer

The aim of this study was to determine therapy-related risk factors for the development of melanoma after childhood cancer. Among 4401 3-year survivors of a childhood cancer in eight French and British centres and 25120 patients younger than 20 years old at first malignant neoplasm (FMN) extracted from the Nordic Cancer Registries, 16 patients developed a melanoma as a second malignant neoplasm (SMN). A cohort study of the French and British cohorts was performed. In a nested case-control study, the 16 patients who developed a melanoma as a SMN (cases) were matched with 3-5 controls in their respective cohort according to gender, age at the first cancer, the calendar year of occurrence of the first cancer and follow-up. Radiotherapy appeared to increase the risk of melanoma for local doses >15 Gy, Odds Ratio (OR)=13 (95% Confidence Interval (CI): 0.94-174). Regarding chemotherapy, we observed an increased OR for both alkylating agents and spindle inhibitors, OR=2.7 (95% CI: 0.5-14). Children treated for a gonadal tumour as a FMN were found to be at a higher risk of melanoma, OR=8.7 (95% CI: 0.9-86). The adjusted OR for the local radiation dose was 1.07 (95% CI: 1.00-1.15). In conclusion, radiotherapy may contribute to an increased risk of melanoma as a SMN, but only at very high doses of low linear energy transfer radiation. Common genetic origins between gonadal tumours and malignant melanomas are likely.

Radiation dose and relapse are predictors for development of second malignant solid tumors after cancer in childhood and adolescence: A population-based case-control study in the five Nordic countries

The aim of the study was to assess the risk with radiation therapy and chemotherapy of the first cancer in childhood and adolescence for the development of a second malignant solid tumor (SMST). Also, the role of relapse of the primary tumor was studied. It is a nested case-control study within a Nordic cohort of patients less than 20 years of age at first diagnosis 1960 – 1987. SMSTs were diagnosed in 1960–1991. There were 196 cases and 567 controls. The risk was increased only for radiotherapy given more than five years before the development of the SMST. A significantly increased relative risk of 1.8 was found already at doses below 1 Gy. The risk increased rapidly up to a maximum of 18.3 for doses above 30 Gy. Chemotherapy alone did not increase the risk to develop an SMST. However, in combination with radiotherapy, chemotherapy showed a significant potentiating effect. Relapse was found to be an independent risk factor for development of an SMST, with a higher relative risk for females than for males.

SECOND MALIGNANT NEOPLASMS IN DIGESTIVE ORGANS AFTER CHILDHOOD CANCER: A COHORT-NESTED CASE-CONTROL STUDY

PURPOSE Cancers of the digestive system constitute a major risk for childhood cancer survivors treated with radiotherapy once they reach adulthood. The aim of this study was to determine therapy-related risk factors for the development of a second malignancy in the digestive organs (SMDO) after a childhood cancer. METHODS AND MATERIALS Among 4,568 2-year survivors of a childhood solid cancer diagnosed before 17 years of age at eight French and British centers, and among 25,120 patients diagnosed as having a malignant neoplasm before the age of 20 years, whose data were extracted from the Nordic Cancer Registries, we matched 58 case patients (41 men and 17 women) of SMDO and 167 controls, in their respective cohort, for sex, age at first cancer, calendar year of occurrence of the first cancer, and duration of follow-up. The radiation dose received at the site of each second malignancy and at the corresponding site of its matched control was estimated. RESULTS The risk of developing a SMDO was 9.7-fold higher in relation to the general populations in France and the United Kingdom. In the case-control study, a strong dose-response relationship was estimated, compared with that in survivors who had not received radiotherapy; the odds ratio was 5.2 (95% CI, 1.7-16.0) for local radiation doses between 10 and 29 Gy and 9.6 (95% CI, 2.6-35.2) for doses equal to or greater than 30 Gy. Chemotherapy was also found to increase the risk of developing SMDO. CONCLUSIONS This study confirms that childhood cancer treatments strongly increase the risk of SMDO, which occur only after a very long latency period.

Mantle Treatment of Hodgkin's Disease: Results and side effects

Eighty-seven patients were treated with the mantle technique for Hodgkins disease. Usually 40 Gy in 27 fractions in two series over 71 days were given. A local recurrence was diagnosed in 3 of 87 patients. An analysis of radiation reactions of the lung tissue, heart and pericardium, and spinal cord is reported. It is recommended to give mantle treatment for Hodgkins disease over a relatively long period of time such as in split-course in two series.

Mantle treatment. Absorbed dose measurements in patients compared with dose planning.

In vivo dose measurements were performed in the hypopharnyx-oesophagus for 60 adult patients receiving mantle treatment with 60Co. The measurements of absorbed dose in more than 1 600 points were analysed and compared with dose plans for the same patients. For the technique used the mean difference between in vivo measured and planned absorbed dose is within +0.4 and -1.3 per cent with a standard error of the mean of 0.4 per cent.

Radiation sensitivity of tissues irradiated during mantle treatment of Hodgkin's disease.

irradiation of supradiaphragmatic Hodgkin’s disease. It is hoped that this technique will produce better results than the involved-field technique. The value of such improvement may however possibly be reduced by an increased frequency and severity of late adverse effects of radiation, since the mantle field usually includes much more tissue than the involved-field treatment. LANDBERG et coll. ( 1971) in a preliminary report reviewed the literature and described some of the side effects of mantle treatment. The sequelae that have attracted most interest are those due to irradiation of the lung tissue, the heart and pericardium, the nervous system and the bone marrow and to some extent the mucous membranes, the thyroid and cdnnective tissue. This paper reports autopsy findings in different organs within the irradiated volume in two cases that had received mantle treatment with a split-course technique for Hodgkin’s disease. It also reviews the radiation sensitivity of some of these tissues.

Whole-body-casts for patient immobilization in mantle treatment, treatment of the inverted-Y and moving strip

A reliable patient fixation is mandatory in order to minimize the frequency and magnitude of beam geometry mistakes in radiotherapy.2 If large and irregular beams are used such as the upper mantle, the inverted-Y-beams and the moving strip, the treatment may be very prone to such mistakes, which may influence cure rate and side effects.’ Often it is necessary to treat the patient in both supine and prone positions, and such a shift of position further introduces the possibility of a change in both the outline of the patient and the position of internal organs. These two changes also may significantly influence the outcome of therapy. We have used large “whole-body”-casts for some years when treating large fields. The casts cover the patient from above the vertex of the skull down to the thighs. The immobilization and repositioning of the patient has been found to be very good with these large casts as judged from repeat treatment verification films. In case the patient is treated in both supine and prone positions, one cast is made for each position. Both casts are then produced with the patient in one position only. Thus the change of contour upon change of position is minimized. If the patient is treated only in one position with anterior-posterior beams, the low bulk density of the cast has not caused the 8 MV X-ray irradiation to give any detectable skin reaction. With the use of whole-body-casts in the treatment of the upper mantle in combination with individual dose planning with correction for tissue heterogeneity and checking the absorbed dose with extensive in viuo dose measurements only a 3% local recurrence has occurred in Hodgkin’s disease.3 The patient is first placed in prone position on a large sheet of paper, and the vertical outline is then drawn on the paper with a margin of 2 cm. The drawn outline is transferred to a 100 x 50 x 15 cm3 large styrofoam block. The block is cut vertically with a heated wire along the patient’s outline. The bottom of the cut block is sealed with a 2 cm thick Styrofoam slice and the two pieces are glued together. Pieces are cut

Calculation and measurements of absorbed dose in total body irradiation

A method which is simple, reliable, and rapid to use in clinical routine for basic dose calculation in total body irradiation (TBI) has been tested with 8 MV x-rays. The dosimetry follows, as far as possible, national and international recommendations for conventional radiotherapy. The dose rate at different locations and depths is calculated from the absorbed dose rate at dose maximum for a phantom size of 30 x 30 x 30 cm in the TBI field (Dc), an inverse square law factor (SAD2/SPD2), the tissue-maximum ratio (TMR), an equivalent phantom and patient size correction factor (A), a factor for lack of back-scattering material (B), an off-axis output correction factor (O), and a factor that corrects for off-axis variations in effective photon beam energy and for oblique beam penetration of the patient (R). The collimator opening is constant for all patient sizes. It is shown that TMR, A, B and R can be measured in conventional geometry in ordinary phantoms but at an extended distance, while Dc, O and SAD2/SPD2 must be measured in TBI geometry. Tests in Humanoid phantoms showed an agreement in measured and planned AP/2 doses of 2% or better. If the calculation method is used for lower photon energies or in other TBI geometries it may be necessary to correct for the elliptical shape of the patient and for back-scattered radiation from the walls or floor.

Hodgkin's Disease Irradiated with the Inverted-Y Technique

Thirty-four patients with Hodgkins disease were treated with the inverted-Y technique. Target absorbed dose was 40 Gy given in a split-course schedule to all but one patient. Only one recurrence occurred. Seventeen patients remained symptom-free after treatment and another 9 were rescued by further therapy. Eight patients died. All 7 patients in stages I and II are alive. In stage III A more patients with upper abdominal disease remained symptom-free after treatment than patients with lower abdominal disease. Of 7 patients in stage III B, 5 died. Actuarial survival at 10 years was significantly better for patients without systemic symptoms. Radiation side effects were mild. One serious complication occurred, acute gastrointestinal ulceration in the patient given the total dose in one series. No permanent symptom-producing side effects from liver, kidneys, spinal cord or bone marrow occurred.