Hywel Madoc-Jones

Radiation therapy alone in the treatment of carcinoma of the uterine cervix. II. Analysis of complications

A retrospective analysis was carried out on 811 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. A correlation was made of the doses of irradiation delivered to the pelvic organs with external beam and intracavitary insertions. Approximately 3% of the patients exhibited grade 2 gastrointestinal complications, and 2% developed grade 2 urinary complications; 5% of the patients developed grade 3 gastrointestinal complications, and 3% developed grade 3 urinary complications. Other types of complications, primarily grade 2, such as vaginal necrosis, pelivic abscess, thrombophlebitis, etc, were seen in approximately 5% of the patients. Thus, the total percentage of patients developing grade 2 complicatins was 10% and grade 3 complications, approximately 8%. About 25% of the patients who had complications showed more than one sequela. The most frequently observed grade 2 complications were proctitis, cystitis, vaginal stenosis, and partial small bowel obstruction which were treated with conservative management. Grade 3 complications required surgical treatment and consisted most frequently of ureteral stricture, vesicovaginal fistula, rectovaginal fistula, sigmoid stricture, small bowel obstruction, proctitis, and large rectal ulcers. The most significant factor affecting the appearance of complications was the total dose of irradiation delivered to the pelvic organs by the whole pelvis external irradiation and intracavitary insertions. With maximum total doses up to 8000 rad the incidence of grade 2 and 3 complications was less than 5%. However, with higher doses the incidence of complications increased to 10% to 15%. In patients receiving total doses of 6000 rad to the bladder or rectum, more complications were noted when only one intracavitary insertion was performed, as compared with two or three. Eighty percent of the rectosigmoid complications occurred within 30 months of initial therapy, in contrast to 48 months for the urinary complications. Patients who developed complications had survival rates comparable to those without complications. This underscores the need to rapidly institute treatment on patients who have severe injury after radiation therapy. Even though it is difficult to determine the exact total dose delivered to a specific volume within the pelvis, the current study strongly indicates that dose calculations to specific anatomical points may be reliable parameters to use in modifying treatment techniques to deliver doses of irradiation that will not exceed tolerance limits for the pelvic structures, when treating patients with carcinoma of the uterine cervix with irradiation alone.

Radiation therapy alone in the treatment of carcinoma of uterine cervix I. Analysis of tumor recurrence

This is a retrospective analysis with emphasis on the patterns of failure in 849 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. In 281 patients with Stage IB tumors, the total incidence of pelvic failure was 6.4% (two without and 16 combined with distant metastasis). In 88 patients with Stage IIA, 12.5% failed in the pelvis (one without and ten combined with distant metastasis). The total pelvic failure rate in Stage IIB was 17.4% (22 without and 22 combined with distant metastasis). In 212 patients with Stage III, the overall pelvic failure rate was 35.8% (31 without and 45 combined with distant metastasis). Approximately 25% of the pelvic recurrences were central (cervix or vagina) and 75% parametrial. The overall incidence of distant metastasis was 13.5% for Stage IB, 27.3% for Stage IIA, 23.8% for Stage IIB, and 39.6% in Stage III. Higher doses of irradiation delivered to the medial and lateral parametrium with external beam irradiation and intracavitary insertions were correlated with a lower incidence of parametrial failures in all stages, except IB. In Stage IIA, medial parametrial doses below 9000 rad resulted in 10/78 = 12.8% pelvic failures, in contrast to one recurrence in 10 patients treated with doses over 9000 rad. In Stage IIB, doses below 9000 rad yielded a pelvic recurrence rate of 36/203 (17.7%) compared to 5/49 (10.2%) with higher doses. In Stage III there were 66/167 (39.5%) recurrences with doses below 9000 rad and 10/44 (22.7%) with larger doses. Statistically significant differences were observed among the Stage IIB (P = 0.02) and III patients (P = 0.005) respectively. The lateral parametrial dose also showed some correlation with tumor control, although the differences were not statistically significant. The survival in patients with Stage IIB and III was 10% higher in the patients treated with higher parametrial doses. However, the differences are not statistically significant. These results strongly suggest that higher doses of irradiation must be delivered to patients with Stage IIB and III, but improvement in tumor control must be weighed against an increasing number of complications. Factors other than the total doses of irradiation, such as the characteristics of the tumor and the quality of the intracavitary insertion influence the therapeutic results in irradiation of carcinoma of the uterine cervix. Other therapeutic approaches must be designed to improve the effect of irradiation in the tumor without further injury to the normal tissues. Hypoxic cell sensitizers, hyperthermia and high LET particles are under investigation.

FURTHER FOLLOW-UP OF RESULTS OF TREATMENT IN 90 LAPAROTOMY-NEGATIVE STAGE I AND II HODGKIN'S DISEASE PATIENTS: SIGNIFICANCE OF MEDIASTINAL AND NON-MEDIASTINAL PRESENTATIONS

Abstract A preliminary report described the results of radiotherapy treatment in 90 patients with laparotomy-negative stage I and II Hodgkins disease. 15 This group has now been followed a minimum of five years. The maximum follow-up is just over ten years. The findings in the preliminary report are now confirmed. The projected ten year survival is approximately 93%; the projected ten year disease free survival is about 60%. None of the patients received total nodal radiotherapy. More than half of the patients received no elective irradiation below the diaphragm and some of them received less than full mantle treatment. Present philosophy in the management of Hodgkins disease is tentatively based on combining the results of the treatment of patients variously staged, either with or without laparotomy or with or without lymphangiography. Analysis of patterns of failure in patients who have had a laparotomy strongly suggest that a more conservative radiotherapy approach than is currently the norm in most institutions can be equally effective. Indications for a combined chemotherapy/ radiotherapy program for mediastinal presentations is discussed.

Correlation between radiation dose and tumor recurrence and complications in carcinoma of the uterine cervix: Stages I and IIA

Abstract A retrospective analysis is reported on 330 patients with carcinoma of the uterine cervix, 23 with Stage IA, 233 with Stage IB and 74 with Stage IIA disease treated with irradiation alone. The dose of irradiation delivered to the cervix, paracervical tissues or the pelvic lymph nodes was correlated with tumor control. There were no central or parametrial failures in patients with Stage IA disease. There were 4 local or marginal (central) recurrences (1.6%) and 15 (6.5%) parametrial failures in the patients with Stage IB disease. Of 74 patients with Stage IIA disease, 3 developed cervical failures (3.9%) and 4 had both central and parametrial recurrences (5.2%). A definite correlation was found between the dose of irradiation delivered to the pelvic lymph nodes and the incidence of recurrences in the patients with Stage IB disease, (about 20%) parametrial failures with doses below 4000 rad in contrast to about 5% with 4000–5000 rad and 2% with doses over 6000 rad). Among patients with Stages IB and IIA disease, the survival of those who were treated with radiation alone and who received doses less than 4000 rad was about 10% less than patients who were treated with higher doses. This difference is not statistically significant; however, it suggests strongly that higher doses of irradiation to the parametria correlate with better tumor control in the pelvis and survival. Complications were slightly higher with doses to the bladder or rectum over 8000 rad. Although it was not statistically significant, patients who had non-standard intracavitary insertions had approximately 18% complications in contrast to only 6.6% in 135 patients with adequate insertions. Factors other than total dose of irradiation, such as geometry of the pelvis, characteristics of the tumor, position of the applicator, type of applicators used, loading and dose rate are important in evaluating the effects of irradiation in tumor control and complications of carcinoma of the uterine cervix.

Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia : Results of daily and intermittent fractionation with and without concomitant hydroxyurea

Seventeen patients with either chronic myelogenous leukemia (CML) or myelofibrosis with myeloid metaplasia (MMM) received 24 courses of splenic irradiation at this institution from 1973 to 1982. Eleven of the 17 patients had received prior chemotherapy. Patients were treated with 60Co gamma rays or 6 MV photons. The fraction size ranged from 15 to 100 rad and the total dose per treatment course from 15 to 650 rad, with the exception of one patient who received 1650 rad. Fourteen of 19 courses (71%) given for splenic pain yielded significant subjective relief while 17 of 26 courses given for splenomegaly obtained at least 50% regression of splenic size. Blood counts were carefully monitored before each treatment to limit hematologic toxicity. From this experience, the authors conclude that splenic irradiation effectively palliates splenic pain and reverses splenomegaly in the majority of patients with CML and MMM. Intermittent fractionation (twice or thrice weekly) is more convenient for the patient, appears to be as effective as daily treatment, and may be associated with less hematologic toxicity. Preliminary results of concurrent treatment with splenic irradiation and oral hydroxyurea show promise and warrant further study.

Monte Carlo Based Dosimetry and Treatment Planning for Neutron Capture Therapy of Brain Tumors

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces (with RBE weighting) a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction. With parallel-opposed lateral irradiation, the planar advantage depth contour for this beam (with the B-10 distribution defined above) encompasses nearly the whole brain. Experimental calibration techniques for the conversion of normalized to absolute treatment plans are described.

Total body irradiation not effective in inclusion body myositis

Four patients with inclusion body myositis were treated with 150 rad of total body irradiation given in 5 weeks. One patient responded subjectively and transiently, but no patient showed clear benefit. This treatment is not recommended for inclusion body myositis.

Boron neutron capture therapy and radiation synovectomy research at the Massachusetts Institute of Technology Research Reactor

In this paper, current research in boron neutron capture therapy (BNCT) and radiation synovectomy at the Massachusetts Institute of Technology Research Reactor is reviewed. In the last few years, major emphasis has been placed on the development of BNCT primarily for treatment of brain tumors. This has required a concerted effort in epithermal beam design and construction as well as the development of analytical capabilities for {sup 10}B analysis and patient treatment planning. Prompt gamma analysis and high-resolution track-etch autoradiography have been developed to meet the needs, respectively, for accurate bulk analysis and for quantitative imaging of {sup 10}B in tissue at subcellular resolutions. Monte Carlo-based treatment planning codes have been developed to ensure optimized and individualized patient treatments. In addition, the development of radiation synovectomy as an alternative therapy to surgical intervention is joints that are affected by rheumatoid arthritis is described.

Ultrasound used for assessing the in situ position of intrauterine tandems

Intracavitary radiation is an integral part of the treatment in many gynecologic cancers. The intrauterine tandem has a well-established role in treating both cervical and endometrial malignancies. The effectiveness of this therapy and its complications are directly related to the proper intracavitary position of the tandem. To date, there has been no objective technique appropriate for routine use in assessing the precise in situ location of these devices, apart from plain abdominal films. As such, little is known about the incidence or types of procedural complications and the sequelae associated with improper tandem placement. Here it is reported that ultrasound is an effective tool for evaluating the in situ position of the intrauterine tandem. Two cases are presented demonstrating important applications of this method.

Preparations for Clinical Trials at the MIT Reactor and the New England Medical Center

The NEMC/MIT group is planning to initiate Phase I clinical trials of BNCT for deep-seated melanoma on the extremities. These trials will be carried out using the epithermal neutron beam at the 5 MW MIT Research Reactor (MITR-II). This paper outlines some of the preparations for these trials.