Therapeutic dosimetry for Cf-252 neutron brachytherapy of pelvic cancer.

252Cf (Cf) was used to treat tumors of the cervix and uterus with neutron brachytherapy (NT) in an ongoing clinical trial. Tandem and ovoids insertions were used and combinations of single and multiple applications along with high dose whole pelvic irradiation. Dosimetric analysis of treated cases for patterns of tissue dose were carried out. Tissue dose for Cf-NT was, in general, high for neutron components in the central pelvis only, and fell off rapidly with distance from the applicators. The majority and balance of therapeutic dose was contributed by low linear energy transfer (LET) high energy photon beam radiation to the whole pelvis. Comparison with fast neutron beam therapy (NBT) isodose curves showed that much more homogeneous neutron dose was delivered to the pelvic tumor and organs by NBT. Complication frequency has been reported to be higher for neutron beam therapy than for Cf-NT. It appears that the higher integral neutron biological dose to normal tissues for NBT compared to intracavitary Cf-NT probably contributed to the frequency of side effects.

RTOG Phase I study on fast neutron teletherapy for squamous cell carcinoma of the esophagus.

From August, 1977, through January, 1981, the Radiation Therapy Oncology Group sponsored a Phase I study (RTOG 77-09) on the use of fast neutrons for treating inoperable squamous cell carcinomas of the esophagus. A total of 39 evaluable patients were treated with curative intent using either fast neutrons alone or in combination with low LET irradiation as part of a mixed beam fractionation scheme. Actuarial survival curves are presented for both the "neutrons alone" and the "mixed beam" treatment groups. There was no significant survival difference between these groups of patients. The projected survival at two years is less than 10%, which is comparable with megavoltage photon results for an unselected series of patients. The size of the primary lesion and the initial Karnofsky performance status were found to be the most important prognostic indications for prolonged survival. Sixteen of 39 patients were felt to have achieved local clearance of their tumor at some time during their follow-up with the median time until a local recurrence being 17 months. Treatment related complications and patterns of metastatic spread are discussed. In general, it appeared that the response of large tumors to neutron irradiation resulted in necrosis and fistula formation. In many cases this was accompanied by persistent/recurrent tumor within the high dose radiation volume.

Carcinoma of the cervix: surgical staging and radiotherapy with 32 MeV betatron.

Fifty-six patients with squamous cell carcinoma of the cervix were staged by exploratory laparotomy. Twenty-eight of them received radiotherapy with 32 MeV Betatron and intracavitary radium. Twenty-one patients with Stage IB or IIA had a radical hysterectomy, five had post-operative pelvic irradiation, and two had primary exenteration. An overall 23.2% of patients had metastases in the paraaortic fields. Four patients with paraaortic node disease received extended field irradiation: 4500 rad in 5 weeks to paraaortic nodes. Two of them are alive and disease-free at 5.5 to 6.5 years.

Comparison of dose-time-fractionation schemes in non-oat cell lung cancer.

A series of 205 patients with inoperable, non-oat cell carcinoma of the lung were treated with three different dose-fractionation schedules. Fifty-six patients received 5000 rads in 25 fractions over five weeks (continuous, A); 79 patients received 2000 rads in five fractions over five days, with two weeks' rest, followed by 2000 rads in five fractions over five days (split-course, B); 70 patients received 3000 rads in 10 fractions over two weeks, followed by three weeks' rest and another 3000 rads (split course, C). The 24-month survival was 33% for A, 15% for B and 25% for C. The split course was better tolerated and radiation fibrosis was dose-related.

Radiotherapy and head and neck cancer. Role of lymphocyte respontse and clinical stage.

The mean number of lymphocytes, response to phytohemagglutinin (PHA), and response to concanavalin A (Con A) in whole-blood cultures for 106 patients with head and neck cancer were 83%, 73%, and 64%, respectively, of values for healthy control individuals. During radiotherapy, lymphocyte counts declined to 44% and PHA and Con A responses declined to about one third of control values. Lymphocyte counts slowly increased after treatment to 77% of control values after two years, but responses to mitogens remained at about 40%. Responses to PHA and Con A for 38 patients who lived beyond 18 months were significantly greater before and after treatment than responses for 39 patients who died within 18 months. In general, a poor pretreatment response to PHA and Con A correlated with a poor clinical course, whereas responses near the control level indicated a good clinical course.

Correlation between macrophage intracellular electrical potentials and malignant melanoma growth in a murine model.

Peritoneal macrophages were collected from mice at varying periods after transplantation of an allogeneic malignant melanoma in the hind limb. The intracellular electrical potentials of these macrophages were measured and a correlation was found to exist between tumor growth measured by size and pathological examination, and the development of large negative intracellular potentials. We propose that this change in intracellular potential is correlated with changes in the immune system and may be triggered by membrane permeability changes possibly in response to calcium ions.

Lymphokine-induced changes in macrophage transmembrane electrical potentials.

Intracellular electrical potentials have been measured in nonactivated and immunologically-activated macrophages obtained from the peritoneal cavities of mice. Normal macrophage potentials were established and found to become significantly more electronegative after in vitro exposure for 10 minutes to a lymphokine-containing supernatant which induced macrophage activation. This approach may reflect very early concomitants of such activation and is also useful in the study of other immunologic systems.

Preliminary report of the M. D. Anderson Hospital/Texas A & M variable energy cyclotron fast-neutron therapy pilot study.

The records of 248 patients treated with fast neutrons and of 102 comparable but nonrandomized control patients treated conventionally with photons, surgery, or combined surgery and photon irradiation were reviewed. Fast neutron therapy included treatment with neutrons alone, a neutron boost after photon therapy, or a schedule of alternating neutron and photon treatments (mixed beam). The results with mixed beam irradiation were superior to those obtained with the other neutron therapy techniques, and compared favorably with the results of standard treatment methods. However, the lack of a conclusive advantage for neutron therapy in this pilot study illustrates the need for on-going randomized clinical trials.

Stereotactic implantation of iridium192 into CNS neoplasms.

A new method of stereotactic implantation of Iridium192 into CNS neoplasms is presented along with a method for tumor localization by computerized axial tomography, stereotactic angiography and stereotactic serial biopsies. A case treated with this technique is presented with an encouraging short term result.

Lymphocyte response in patients with head and neck cancer: effect of clinical stage and radiotherapy.

Ffty-three patients with head and neck cancer tested before radiation treatment to determine numbers of blood lymphocytes and immunologic responses to mitogens of lymphocytes in whole-blood cultures had mean values that were 19% to 26% less than values for healthy individuals. Thirty patients whose disease was in stages III or IV had values similar to those in 23 patients whose disease was in stages I or II. Values for 45 patients tested at end of radiotherapy decreased to about 50% of pretreatment values; however, patients with advanced lesions experienced greater decreases (to 24% to 50%) than patients with localized lesions (to 71% to 84%). Patients with advanced lesions usually received radiation to larger areas than patients with localized lesions; therefore, the extent of decline in laboratory values was most likely dependent on volume of tissue treated.

Effect of therapeutic radiation on peripheral blood lymphocytes in patients with carcinoma of the breast.

Effects of radiation therapy for carcinoma of the breast on responsiveness to mitogens of blood lymphocytes of patients at different clinical stages were analysed. Patients at different clinical stages had comparable numbers and responses of lymphocytes. During therapy the mean lymphocyte numbers decreased to 31 per cent of the pre-treatment value and mean responses to mitogens in whole-blood cultures decreased to 15 to 39 per cent of pre-treatment values. Similar decreases occurred whether or not mastectomy was performed.