The value of postoperative radiotherapy as an adjuvant to radical neck dissection.

In this study the results of combined radiotherapy and surgery are compared with the results of surgery alone in patients with neck node metastases from squamous cell carcinomas of the head and neck region. Postoperative radiotherapy decreases the recurrence rate in the neck, especially in cases with histologically established extranodal spread. Results of preoperative radiotherapy were similar to those of irradiation after surgery. Postoperative radiotherapy is favored, because it allows a selection of patients for extra treatment on the base of prognostic information, provided by the histologic characteristics of the neck dissection specimen.

Clinical data from irradiated growing long bones in children.

The growth retardation following irradiation of long bones during childhood has been studied. In 9 patients, irradiation was given for treatment of hemangioma localized in the extremities. In another 13 patients, irradiation was administered because of different malignancies localized either in the long bones themselves or in the soft tissues surrounding the epiphyseal plates. The deficit in growth of the irradiated extremity could, in most of the patients, be assessed at the time when the period of growth was completed. An attempt was made to derive dose-effect curves as a function of the age of the children at the moment of irradiation and the administered irradiation dose. When the parameter used for estimating the radiation effect was the shortening of the irradiated extremity as compared to the unirradiated one, the effect was greater in younger bones. However, when the growth remaining after irradiation was taken into account the age at irradiation did not influence the final effect, the dose of irradiation being the most important factor.

Effect of hyperthermia and misonidazole on the radiosensitivity of a transplantable murine tumor: influence of factors modifying the fraction of hypoxic cells.

Hypoxia has been demonstrated to play an important role in the effect of hyperthermia on tumors. We have studied the influence of different factors modifying the oxygenation status of a transplantable murine mammary adenocarcinoma (tumor volume and pentobarbital sodium anesthesia). The effect of hyperthermia alone on the tumor is not significantly influenced by the change in oxygenation status during the growth of the tumor. Also, the large increase of the acutely hypoxic cell fraction, as a result of anesthesia, does not change the effect of hyperthermia alone. In the combined irradiation-heat treatment there is a clear influence of the chronically hypoxic cell fraction on the response to hyperthermia: an increase in tumor size, resulting in a larger hypoxic cell fraction, leads to an increase in thermal enhancement ratio. However, the increased acutely hypoxic cell fraction, resulting from anesthesia, did not lead to an increase in thermal enhancement ratio; in fact the enhancement ratio apparently decreased. In spite of the fact that hyperthermia was applied immediately after irradiation no potentiation of radiation effects was found. The thermal enhancement of the radiation response was never larger than the enhancement as a result of misonidazole. All thermal enhancement could be explained by effects of heat on the chronically hypoxic cell fraction. Misonidazole had no effect on the response of tumors to heat alone, but greatly enhanced the effect of heat combined with irradiation. Anesthesia of the animals did not influence these effects of misonidazole.

Radiotherapy of lymph node metastases in patients with squamous cell carcinoma of the head and neck region.

The results of radiotherapy alone in 233 patients with lymph node metastases of squamous cell carcinoma in the head and neck region were examined. It appeared that the recurrence rate in the neck was mainly related to: localization of the primary tumor; the recurrence of the primary tumor; the radiation dose; and the presence of a residual palpable tumor mass in the neck 6 weeks after radiation. The optimum radiation dose was about 2000 ret. An isoeffect curve was calculated, which differed only slightly with the nominal standard dose (NSD) formula. Elective irradiation of the contralateral neck appeared to diminish the outgrowth of neck node metastases at the side. Changes in the radiation treatment in the last treatment period, such as a higher radiation dose and a larger treatment area, resulted in a lower recurrence rate for the neck node metastases, and also in a higher survival rate.

Dose-effect relations for tumour control and complication rate after fast neutron therapy for pelvic-tumours.

The effects of fast neutrons and high-energy photons were analysed for tumour control and skin and bowel damage after treatment of bladder and rectal cancers. A combination of statistical models was used for this analysis. A steep dose-effect curve was found for local tumour control as well as for the risk of complications. Some estimates were made of RBE values for control of bladder tumour and for normal-tissue damage. The implication of these data for neutron therapy is discussed.

Radiosensitivity of microscopic tumours of a transplantable mammary adenocarcinoma in mice.

Evidence is presented that microscopic tumours (of a transplantable murine mammary carcinoma, M8013X) grow faster than larger, palpable, tumours. Microscopic tumours are also more radiosensitive than larger tumours. The decrease in radiosensitivity in larger tumours is prevented to a large extent by misonidazole, which has no significant effect on the radiosensitivity of microscopic tumours. The retardation in growth rate which occurs after the fast microscopic growth is probably related to the appearance of hypoxic cells. Both the decrease in growth rate and the progressive development of hypoxia may be caused by the relatively poorer blood flow in larger tumours. Part of the radioresistance in "large" tumours ( approximately 250 mm3) seems to be due to factors other than hypoxia; maybe cell-kinetic factors also play a role. The intrinsic radiosensitivity of tumour cells in microscopic tumours was assessed by means of a modified latency test: the Dq and Do were 2.2 and 2.5 Gy respectively. A number of factors which may influence the reliability of these estimates are discussed.

Prophylactic irradiation of the lungs to prevent development of pulmonary metastases in patients with osteosarcoma of the limbs.

A controlled clinical trial conducted by the European Organization for Research on Treatment of Cancer Radiotherapy Cooperative Group has shown that prophylactic lung irradiation is effective in preventing lung metastases in patients under 17 years of age. Recently, a new three-armed trial has started in which prophylactic chemotherapy and lung irradiation and chemotherapy combined with radiotherapy to the lungs will be compared for their ability to prevent the development of lung metastases.

Preliminary results in advanced head and neck cancer with radiotherapy by multiple fractions a day.

Nine patients with advanced head and neck cancer have been treated by irradiation consisting of three fractions a day of 180 rad administered with intervals of 4 h. The total dose was 4860--5400 rad in an overall time of 11--12 days. The acute mucosal reactions produced by this multifractionated schedule were similar to those observed with conventional fractionation. The acute skin reactions were minimal. The period of acute reactions were shorter than is generally observed with conventional fractionation. In six patients with a follow-up time of six months or longer no late reactions have been detected with the exception of one patient requiring permanent tracheostomy because of laryngeal oedema. In the whole group of patients loco-regional control of the disease has been achieved. Six patients have maintained the full response for six months or longer. The results so far obtained with this multiple fractions a day schedule are encouraging. More patients have to be entered in this study in order to draw definitive conclusions.

Role of metastatectomy without chemotherapy in the management of osteosarcoma in children.

In a series of 18 consecutive non metastatic osteosarcoma patients, metastases developed in 12 and successful metastatectomies could be performed in 6. No adjuvant chemotherapy was given. Four of these 6 patients survived. The importance of length of disease-free survival is described. Radiotherapy and chemotherapy as adjuvants to prevent or postpone the development of metastases are mentioned and an EORTC-SIOP trial on this subject is briefly discussed.

Dose-modifying effect of misonidazole on the radiation response of growing cartilage in mice.

Misonidazole administered before a single dose of 15 Gy X-rays enhances the radiation response of growing bone in mice by a factor 1.3. In combination with split-dose irradiation of twice 7.5 Gy the drug did not cause significant enhancement. These results are most likely due to the existence of hypoxic cells in growing cartilage as has been demonstrated already by other authors.