Conformation therapy using a computer controlled telecobalt unit for advanced cervical carcinoma.

This retrospective analysis evaluates the results of conformation radiotherapy for patients with advanced cervical carcinoma. Between January 1980 and September 1987, 16 patients with high common iliac/para-aortic node metastases from advanced carcinoma of the uterine cervix were treated using conformation radiotherapy. A large area from L1/L2 to the pelvis, with an average length of 23 cm, was treated to a total tumour dose of 5000-5500 cGy, with a daily tumour dose of 180-200 cGy in 28-30 daily fractions, using a computer controlled tracking cobalt unit (CCTCU). Before external beam irradiation, 11 patients underwent laparotomy/hysterectomy, seven were given chemotherapy and eight received brachytherapy. The preliminary results are encouraging. The actuarial 1-year, 3-year and 5-year survival rates after treatment were 81%, 44% and 37%, respectively. The locoregional control rate was 62.5%. None of the patients relapsed in the para-aortic nodes. All patients tolerated the large area of tracking irradiation therapy very well. None had any severe acute or delayed radiation complications. Use of the conformation radiotherapy technique to include the pelvic and para-aortic nodes has been shown to be an effective form of radiotherapy with minimal morbidity.

Incidence of cataracts after single fraction total body irradiation: the role of steroids and graft versus host disease.

Eighty-eight patients who received single fraction total body irradiation (sfTBI) as part of their conditioning for allogeneic BMT have been evaluated for the risk of cataract formation. Thirty-eight (43%) have developed cataracts; 11 required surgery. With 9.5-13.6 years follow-up (median 10.7 years), all 12 recipients of unmanipulated marrow allografts have developed cataracts; the actuarial risk of needing surgery was 32 (+/- 18%, 95% confidence intervals (CI)). Ten of these 12 required high-dose steroids (prednisolone > 1 mg/kg/day) for the treatment of GVHD. Seventy-six patients received T cell-depleted allografts; 14 of 76 required post-transplant immunosuppression with high-dose steroids. With 1-9.4 years follow-up (median 5 years), the actuarial risk of cataract formation in T cell-depleted allograft recipients is 72% (+/- 52% CI), the actuarial risk for needing surgery is 20% (+/- 9% CI). Recipients of sfTBI and non-T cell-depleted allografts had a significantly greater risk of developing cataracts (p = 0.003, long rank test) and of needing surgery (p < 0.05, log rank test) than patients receiving T cell-depleted BM. Cataracts occurred more frequently in patients requiring post-transplant immunosuppression with steroids (relative risk 2.12, p < 0.01 log rank test).

Graft rejection following HLA matched T-lymphocyte depleted bone marrow transplantation.

Bone marrow graft rejection following HLA-matched bone marrow transplantation (BMT) for leukaemia has been a rare problem. However, with the introduction of T-lymphocyte depleted BMT, graft rejection is recognized as a new complication. At the Royal Free Hospital (RFH) in London T-depletion is achieved using two monoclonal antibodies with complement mediated lysis. The methodology was extended to other centres and in total 56 patients have received T-depleted, HLA matched BMT. Twelve of 56 patients have had graft rejection. At the RFH three of 41 (7%) patients have had rejection whereas at collaborating centres nine of 15 (60%) patients have had rejection. We have investigated these rejections in order to identify factor(s) responsible. Rejection was not restricted by patient or donor characteristics, nor disease status. Patient management, chemotherapy conditioning, efficiency of T-depletion, graft versus host disease (GvHD), and infection post BMT, were not consistently implicated. The major difference between the RFH and all other centres was in the radiotherapy (RT) conditioning: The RFH prescribed a single fraction of 7.5 Gy total body irradiation (TBI) whilst collaborating centres gave 10 or 12 Gy fractionated TBI. We conclude that the different incidence of rejection (7% v. 60%) relates primarily to the RT conditioning although the mechanisms(s) of rejection remain unknown. We conclude that where T-depleted BMT is used, compensation by more intensive RT conditioning is required in order to avert graft rejection.

Conformation therapy: a method of improving the tumour treatment volume ratio.

Restriction of the volume irradiated is a fundamental tenet of radiotherapy. Conventional two-dimensional treatment results in geometrically shaped high-dose regions, the sizes of which are defined by the greatest dimensions of a tumour mass. Conformation therapy permits a tumour to be considered for treatment as multiple short segments, and the radiation field to be tailored to fit each segment accurately. This paper demonstrates that this results in a reduction of the treatment volume of between 10% and 80%, depending on the shape of the tumour. Also, it is shown that a greater proportion of the high-dose region is occupied by tumour, thus reducing the volume of normal tissue treated to a high dose. Smaller treatment volumes allow the prescription of tumoricidal doses and improve the tolerance of radiation by patients.

Treatment of medulloblastoma using a computer-controlled tracking cobalt unit.

Radiation therapy of the length of the spinal column presents various clinical and physical problems. The completed plan may be complicated to set up, be time-consuming and require daily variation to achieve reasonable dose homogeneity. A case of medulloblastoma is used to illustrate the steps in producing a plan for dynamic treatment using a computer-controlled tracking cobalt unit. After definition by computed tomography, the target is considered in segments in order to develop a plan which keeps the spinal cord constantly positioned at the beam isocentre. The main computer is used to develop the patient treatment file and information is transferred to a second computer which controls and monitors the safe functioning of the cobalt unit. The cranial fields are treated separately in a conventional way. Good and consistent control of the dose distribution is achieved along the entire target volume. This technique is a marked improvement over all existing methods of treating the spinal axis.

Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukaemic marrow transplant recipients.

For more than 15 years preclinical studies have suggested that acute graft-versus-host disease (aGvHD) might be prevented by the removal of immunocompetent T lymphocytes from the donor marrow inoculum. To test this observation in man 14 patients were given marrows virtually (greater than 99%) depleted of identifiable donor marrow T lymphocytes by the use of a "cocktail" of specific anti-T-cell monoclonal antibodies (MBG6 and RFT8) and rabbit complement. Patients were not given immunosuppressive prophylaxis after bone-marrow transplantation. Moderate to severe (grades II-IV) GvHD was totally prevented. 2 of 13 evaluable patients showed mild (grade I) skin GvHD only. Although peripheral blood recovery was slower than that obtained with other forms of GvHD prophylaxis, no fatal infections occurred. All patients survived the early post-transplant period.

Five years hospital experience with the Amersham caesium 137 manual afterloading system.

The Amersham caesium 137 manual afterloading system for treatment of cancer of the uterine cervix and endometrium has been in use at the Royal Free Hospital for more than five years. The system uses permanently loaded flexible source pencils in combination with standard packs of disposable plastic applicators. Both sources and applicators have proved trouble-free in use. The sources are transported in special containers designed and built at the Royal Free Hospital and are inserted and removed on the ward by nursing staff. A set of sources is used in theatre for rectal and bladder dose measurements when the applicators are inserted. Staff radiation doses are low. The system is mainly used to produce pear-shaped dose distributions similar to those of the Manchester system, but simple cylindrical distributions are possible using symmetrically loaded source pencils.

Seventh interim progress report of the british institute of radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

A fresh analysis of the data entered into the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngopharynx has been undertaken. Completed records of the 732 patients initially entered into the trial have now risen from 687 at the last report to 706. The data have been analysed in a manner similar to that adopted previously so as to measure the effects of the two regimes on both tumour and normal tissues, and some additional analyses have now also been made. There have been some modifications in the results in the various sub-groups which may be due to an inadequate number of patients having been followed up for long enough at the time of the previous analyses. More data for late radiation damage to normal tissues and new radiobiological findings have suggested possible explanations for the differences which have emerged between the two groups. The apparent differences between the sub-groups containing patients with highly localized tumours, which were reported in our previous report, are now less marked and not statistically significant.

Use of anti-T-cell monoclonal antibody OKT3 to prevent acute graft-versus-host disease in allogeneic bone-marrow transplantation for acute leukaemia.

Seventeen patients who received allogeneic bone-marrow transplants from matched or slightly mismatched (in four patients) siblings were observed for at least 60 days or until acute graft-versus-host disease (GvHD) developed. All donor marrows after preliminary manipulation were incubated with 1 mg of the murine monoclonal antibody OKT3 before infusion in an attempt to deplete them of immunocompetent T lymphocytes (opsonisation). In three of the seventeen patients acute GvHD of grade II or greater developed. Two of these patients died, but they had disseminated cytomegalovirus infection as well as GvHD. Eleven patients showed no evidence of acute GvHD, and four had transient limited skin rashes (grade I GvHD). Opsonisation of T lymphocytes has reduced the incidence of severe acute GvHD in this unit from 79% in an earlier group of 14 patients to 18% when added to prophylactic methotrexate.

Conformation therapy at the Royal Free Hospital. A progress report on the tracking cobalt project.

A computer-controlled tracking cobalt unit (CCTCU) was commissioned for treating patients in January 1980. The system has proved to be reliable and acceptable in routine use for conventional and conformation therapy. The system comprises a modified TEM MS90 Mobaltron, a Hewlett-Packard System 1000 Model 30 mini-computer and user programmes. Tracking techniques are suitable for the treatment of tumours of the oesophagus, thyroid, bronchus, chains of lymph nodes or medulloblastoma. Tumours 85 cm long can be treated at the isocentre. The high dose volume may be considerably reduced when tracking techniques are used instead of conventional techniques. The major obstacle to the routine use of conformation therapy is treatment planning. Work in progress is designed to produce a computerized planning system linking a CT scanner and the CCTCU. It is expected that the system will produce both a plan optimized in 3-D and the necessary control data in machine readable form within an hour of a patient being scanned. The present planning system is based on a Rad-8 planning system and an Alderson phantom to verify the dose distribution in 3-D. An outline of the tracking technique is given. The computer control system is described briefly, with its methods of use for treating patients. Brief reverence is made to work at other centres using conformation therapy.

Sixth interim progress report of the British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

The results are reported of the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx. 687 patient records have been analysed with respect to survival rates, recurrence-free rates and laryngectomy-free rates. For the group as a whole these analyses show no difference between the two fractionation regimes. Analysis of the sub-group which had early disease confined to the vocal cords does, however, show a better recurrence-free and laryngectomy-free rate for those patients treated with 5F/week, though the survival rate for the two groups remains similar. Acute and late normal tissue reactions are reported for up to six years after treatment. It appears that treatment with 3F/week can be given safely to patients with advanced disease. The differences between the two treatment groups who had early disease of the vocal cords are discussed, but until more data become available in the future the problems raised cannot be resolved.