Halvor Vermund

Treatment of advanced cancer of the head and neck

The combination of radiation plus 5‐FU produced a significantly increased survival in patients with advanced tonsil and intra‐oral cancer compared to patients who received radiotherapy alone. There was no significant difference in survival between these 2 treatment modalities in advanced cancer of the nasopharynx, hypopharynx, extrinsic larynx, or primary unknown. Similarly, there was no significant difference in survival resulting from these 2 methods of treatment in patients with T1 and T2 as well as T4 head and neck cancers, but a highly significant difference in those with T3 lesions.

Radiation dosage and complications in cervical cancer therapy

Computerized dosimetry in 346 patients treated by a combination of intracavitary and supervoltage radiotherapy has permitted a detailed analysis of dose delivered. The radiation delivered to the bladder, rectum, paracervical area, and the pelvic wall is described for a technique in which a calculated bladder and rectal tolerance was used as the limiting factor for total central dose. Rectovaginal and vesicovaginal fistulas occurred in only 1.4 per cent of the patients, but other serious bowel and ureteral complications were seen in 6.4 per cent. These later complications occurred significantly more frequently when intracavitary therapy was emphasized, producing high paracervical total doses. No individual correlation between dose delivered and complications could be demonstrated.

Mechanisms of action of radiotherapy and chemotherapeutic adjuvants: A review

A review of the rationale for application of combined radiation and chemotherapy in the treatment of certain malignant tumors has been presented. The mechanisms of action of ionizing radiations and many of the commonly employed chemotherapeutic agents are intimately related to the nucleic acid metabolism of proliferating cells. Modification of the DNA‐molecule by certain chemotherapeutic agents results in sensitization of the cell to subsequent irradiation. Reduction in the total number of malignant cells by preirradiation chemotherapy facilitates subsequent radiotherapy of advanced tumors. Certain chemotherapeutic antitumor agents exert a beneficial effect by restraining the growth of distant metastases which often escape clinical detection.

Role of radiotherapy in the treatment of cancer of the tongue. A retrospective analysis on TNM-staged tumors treated between 1958 and 1968.

A total of 154 patients with carcinoma of the tongue received a course of radiation therapy between the years 1958 and 1968. Of these, 112 were previously untreated and 42 had tumors which had been treated previously and persisted. Of these, 20 are alive without disease, 22 died of intercurrent disease without recurrence, 11 of second primary tumors, and 101 of cancer. Thirty‐four of the 42 patients with recurrence and 67 of 112 previously untreated patients died of cancer. Tumors of limited extent without lymph node metastases were controlled by irradiation in 67% of patients (18 of 27 T1T2N0 lesions). Nine of 27 patients with T1T2N0 lesions and 10 of the 22 patients with T3T4N0 lesions died of cancer of tie tongue. The 5‐year survival depended on the extent of the primary tumor varying between 67% for patients with T1N0 to 6 for T4N0 lesions. When the nodes in the neck became clinically involved, the local control rate and the survival rate decreased. However, the majority of patients with an isolated, small, mobile upper cervical node may be cured with radiation therapy (14 of 22 patients with N1 lesions had local control of neck nodes with radiation therapy and only one required radical neck dissection). However, seven of these developed local recurrence in the tongue. Fourteen of the 22 died of cancer. Patients with multiple, bilateral, or fixed cervical nodes have a poor prognosis. We recommend interstitial radiation therapy in early cancers of the tongue, and external high energy beam with supplemental interstitial radiation therapy in the more advanced cases. Weekly examinations of irradiated tumor are carried out to determine if there is any sign of reactivation. If so, radical surgery is performed provided the tumor is operable.

Clinical and theoretical aspects of the treatment of surgically unresectable retroperitoneal malignancy with combined intra-arterial actinomycin-d and radiotherapy

A small pilot series (eight patients) of surgically unresectable retroperitoneal tumors treated with radiotherapy and a selective, prolonged, continuous intraarterial infusion of actinomycin‐D is discussed, in addition to the possible theoretical advantages for this therapy. For such tumors, there is a very low probability of obtaining local control with conventional radiotherapy alone. However, on the basis of recent knowledge from radiobiology and molecular biology, the technique is a rational attempt to improve the local control probability. Geographic miss with radiotherapy portals is another major cause for local failure with such tumors. We also emphasize the importance of detailed tumor localization procedures. The local responses, some of the local controls, the palliation achieved, and the lack of significant morbidity with this technique have been encouraging. We therefore consider it worthy of further clinical investigation.

High-dose radiotherapy for carcinoma of the cervix. Method and results.

A method of radiotherapy of invasive carcinoma of the cervix has been devised utilizing rectal and bladder tolerance as the limiting factor for total central dose. The resulting milligram hours and paracervical doses have been high, especially when intracavitary therapy has been emphasized. The survival statistics on 450 patients treated between 1961 and 1967, mostly by this plan, are good but show that no striking improvement has resulted from the increased doses.

Current Trends in Radiotherapy of Breast Cancer

Abstract Current trends in radiotherapy of breast cancer are toward a greater emphasis on adequate dosage to the internal mammary, supraclavicular and apical axillary nodes after radical mastectomy, especially in tumors with axillary nodes and in tumors without axillary nodes when located in the medial or subareolar regions of the breast. In patients with histologically proved lymph node metastases in the internal mammary and/or apical axillary region, high energy radiotherapy alone may give as good or better five year survivals as extended radical mastectomy with en bloc resection of the internal mammary nodes. Radiotherapy to the chest wall including the operative site is also recommended when radical or simple mastectomy has been performed for locally advanced tumors. Preoperative radiotherapy may be limited to cases of borderline operability. Radiotherapy alone or in combination with palliative surgical resections is favored in lesions which are inoperable due to local extension. In recurrent or metastatic breast cancer radiotherapy may have much to offer, often in combination with hormones or chemotherapy. Newer technics in radiotherapy include the use of supervoltage radiations, radioisotopes and high energy electron beams. In spite of progress in surgery, radiotherapy and hormone chemotherapy, the annual death rate from breast cancer continues to rise, demanding greater efforts to control this disease. Controlled prospective, randomized clinical trials with rigid biometrical designs may be necessary to conciliate some of the present controversies regarding the efficacy of different methods of therapy practiced in different institutions.

MODIFICATION OF IRRADIATION EFFECTS IN THE PIGEON, COLUMBA LIVIA. II. EFFECTS OF DELAYED BONE MARROW IMPLANTATION

Summary 1. Delayed bone marrow transplantation, in contrast to immediate transplantation, resulted in an increased average survival time of approximately 20 days for both homologous and heterologous marrow in lethally irradiated pigeons. 2. Delayed homotransplantation resulted in only partial repopulation by donor derived erythrocytes. Chimera reversal occurred or the proportion of donor erythrocytes in circulation reached a maximum and then declined, while immediate homotransplantations resulted in eventual total repopulation by donor erythrocytes. 3. In the heterologously treated pigeons “in vivo agglutination” occurred between the 4th and 6th day after heterotransplantation regardless of the number of days after irradiation. 4. Delayed heterotransplantation did not result in elimination of all the hosts ertyhrocytes, as was the case for the immediate heterotransplants. However, host-species-specific hemagglutinins were detectable at titers ranging from 8 to 64 with host cells, and sufficiently potent to produce “in vivo agglutination”. 5. The host-species-specific hemagglutinins, which were present in the delayed heterotransplants, disappeared 15 to 20 days after the marrow implant and by the 30th day donor-species-specific hemagglutinins appeared in the circulation. In contrast, the longest survival time after immediate heterotransplantation was 19 days and total repopulation by donor erythrocytes ocurred in all animals which survived 10 days or longer.

RESPONSE OF MOUSE BREAST TUMORS TO L-TRIIODOTHYRONINE AND IRRADIATION

Conclusions 1. Growth rate of transplanted mammary tumor in ZxC57 black F1 hybrid mice treated with L-triiodothyronine was increased. 2. Average life span of tumor-bearing mice receiving L-triiodothyronine was significantly shortened. 3. In mice receiving L-triiodothyronine and x-ray, increased skin reaction was noted. 4. There was no significant difference between average life span of tumor-bearing groups receiving combined irradiation plus triiodothyronine and the group which received local irradiation only.

Modification of Irradiation Effects Through Actively Acquired Tolerance to Homologous Bone Marrow Grafts.

Summary Host and donor pigeons made immunologically tolerant in various combinations by skin grafting shortly after hatching were exposed to lethal doses of irradiation at the age of 8–10 months. Homologous bone marrow transplants gave the following results: 1) The tolerant state of the host did not appreciably affect survival; i.e., mean survival of Group 1 (host tolerant of donor) was 23.4 ± 5.6 and of Group 4 (no known tolerance) was 25.3 ± 4.1 days. 2) Tolerance of marrow donors for host increased mean survival by about 10 days (34.2 ± 4.3 for Group 2 and 35.6 ± 5.2 for Group 3). Differences in mean survival between combined Groups 1, 4 and 2, 3 were statistically significant (p<.05). 3) These data suggest that the immunologic mechanism of the donor is more important than that of the host in producing “homologous disease” in the pigeon.