Multifactorial approach to radiotherapy
Stanley Dische from Mount Vernon Hospital in Northwood gave the Mackenzie Davidson Memorial Lecture in 1991 (Dische BJR 1991; 64(768): 1081-1091) and discussed whether advances in the basic sciences had benefited cancer patients. This paper is worth reading and many of the questions are still relevant. As he says: “We must constantly renew our work otherwise standards of care will fall. It is in this that research is so important.”
The 1990 Silvanus Thompson Memorial Lecture for 1990 was given by Juliana Denekamp from Mount Vernon Hospital in Northwood (Denekamp BJR 1993; 66(783): 181-196) on angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. The early concept that tumour growth was uncontrolled had been recognised to be an oversimplification. She reviewed the multifactorial approach to new radiotherapy protocols that was allowing several different aspects of radiobiological research to be integrated into a single treatment. The effects of prodrug activation, hyperthermia, photodynamic therapy, chemotherapy and cytokines were assessed.
Image source: Denekamp BJR 1993; 66(783): 181-196
Effective imaging is essential for the diagnosis, accurate treatment and follow-up of patients with cancer. In 1994 the Mackenzie Davidson Memorial Lecture was given by Janet Husband from the Royal Marsden Hospital on the imaging of treated cancer (Husband BJR 1995; 68(805): 1-12).
The intrinsic radiosensitivity as a predictor of patient response to radiotherapy was reviewed by CML West from Manchester in July 1995 (West BJR 1995; 68(812): 827-837) and the results were correlated to clinical data.
Charles Joslin commented on brachytherapy in gynaecological cancer in July 1996 (Joslin BJR 1996; 69(824): 689-692) considering clinical dosimetry and the integration of therapies.
The British Institute of Radiology fractionation study
The BIR Fractionation Working party successfully completed two prospective, randomised, multicentre clinical trials of radiotherapy on the treatment of carcinoma of the laryngo-pharynx. This was a major achievement.
The preliminary report had appeared in May 1963 (BJR 1963; 36(425): 382-383). This was an important long-term study and the trial had been thought desirable because some fractionation regimens may produce better results than others and this could be investigated using a prospective study and some fractionation regimens would be economically more desirable or more convenient to the patient.
A report from the BIR fractionation study of 3F/week verses 5F/week in radiotherapy of the laryngo-pharynx was published in February 1990 (Barrett, Dixon-Brown, Goodman, Lawson, Ormsby, Saunders, Williams, Fowler and Wiernik BJR 1990; 63(746): 125-127). The Working Party had been divided into three separate groups (Retrospective Survey, Prospective Trial and Radiobiological Data). The final report of the second BIR fractionation study was published in March 1991 (Wiernik, Alcock, Bates, Brindle, Fowler, Gajek, Goodman, Haybittle, Henk, Hopewell, Hunter, Lindup, Phillips and Rezvani BJR 1991; 64(759): 232-241).
In March 1993 M Rezvani and others (Rezvani, Fowler, Hopewell and Alcock BJR 1993; 66(783): 245-255) looked at the sensitivity of human squamous cell carcinoma of the neck to fractionated radiotherapy and combined and studied the data from the two prospective BIR Fractionation multicentre clinical trials. Of interest was the finding that the longer the overall treatment time was the greater was the chance of recurrence. The influence of radiotherapy treatment time was again discussed by SA Roberts in August 1994 (Roberts, Hendry, Brewster and Slevin BJR 1994; 67(800): 790-794).
Image source: Rezvani, Fowler, Hopewell and Alcock BJR 1993; 66(783): 245-255
There was a considerable interest in different treatment regimens:
In February 1991 DJ Brenner and EJ Hall assessed brachytherapy of the cervix and assessed fractionated high dose rate verses low dose rate regimens (Brenner and Hall BJR 1991; 64(758): 133-141).
GG Khoury and others from Cookridge Hospital in Leeds assessed the combination of radiotherapy and chemotherapy in advanced carcinoma of the cervix (Khoury, Bulman, Joslin and Rothwell BJR 1991; 64(759): 252-260) and in November 1991 the long-term results of Cathetron high dose intracavity radiotherapy was reviewed (Khoury, Bulman and Joslin BJR 1991; 64(767): 1036-1043).
In October 1991 CH Macmillan and others (Macmillan, Carrick, Bradley and Morgan BJR 1991; 64(766): 941-946) assessed concomitant chemotherapy and radiotherapy for advanced carcinoma of the head and neck.
B Jones and others (Jones, Dale, Bleasdale and Davies BJR 1994; 67(800): 805-812) produced a mathematical model for intraluminal and intracavity brachytherapy in August 1994. In September 1996 B Jones and RG Dale looked at mathematical considerations of the reduction of tumour control with increasing overall time (Jones and Dale BJR 1996; 69(825): 830-838).
GP Swanson and others from the Mayo Clinic in Rochester (Swanson, Cupps, Utz, Ilstrup, Zincke and Myers BJR 1994; 67(801): 877-889) discussed the definitive treatment of prostate cancer and gave their results at 15 years after treatment. They expressed the opinion that caution must be used in interpreting any prostate study with less than 10 years of follow-up. M Oldham and S Webb from the Institute of Cancer Research and the Royal Marsden Hospital gave an overview of the optimisation and inherent limitations of 3D conformal radiotherapy treatment plans of the prostate in August 1995 (Oldham and Webb BJR 1995; 68(812): 882-893).
Radiotherapy was becoming increasingly sophisticated. R Ramani and others described in July 1995 the implementation of a multiple isocentric treatment for dynamic radiosurgery (Ramani, O’Brien, Davey, Schwartz, Young, Lightstone and Mason BJR 1995; 68(811): 731-735). This had been introduced in the Toronto-Bayview Regional Cancer Centre in 1988. Such radiosurgery is an example of conformal radiotherapy with stereotactic localisation and precision treatment to minimise the dose to the surrounding normal tissue.
Image source: Ramani, O’Brien, Davey, Schwartz, Young, Lightstone and Mason BJR 1995; 68(811): 731-735
Computers were utilised to operate radiotherapy machines in an increasingly complex manner. In April 1992 AR Hounsell and others (Hounsell, Sharrock, Moore, Shaw, Wilkinson, and Williams BJR 1992; 65(772): 321-326) from the Christie Hospital and Holt Radium Institute described techniques for the computer-assisted generation of multi-leaf collimator settings for conformal radiotherapy. There is a detailed and illustrated description of the technique.
In May 1992 HM Morgan from the Royal Free Hospital (Morgan BJR 1992; 65(773): 409-416) described the necessary quality control needed for such computer controlled radiotherapy treatment.
In February 1995 SW Hughes was describing the use of computers for stereotactic iodine-125 brachytherapy for recurrent malignant gliomas (Hughes, Sofat, kitchen, Brown, Beaney, Timothy, Saunders and Thomas BJR 1995; 68(806): 175-181).
JA O’Donoghue and others gave a most interesting account of the use of 131I radiolabelled meta-iodobenzylguanidine (mIBG) for the treatment of neuroblastoma in 1991 (O’Donoghue, Wheldon, Babich, Boyes, Barrett and Meller BJR 1991; 64(761): 428-434). This technique involves biological targeting of the neuroblastoma with a cytotoxic agent. The dosimetry of such therapy was described by AA Bolster and others in May 1995 (Bolster, Hilditch, Wheldon, Gaze and Barrett BJR 1995; 68(809): 481-490).
In October 1993 DE Bonnett and others from Clatterbridge in Merseyside (Bonnett, Kacperek, Sheen Goodall and Saxton BJR 1993; 66(790): 907-914) gave an interesting account of the second treatment room that had been installed in the MRC Cyclotron unit and its use in the treatment of ocular melanomas. In their first three years of operation over 300 patients had been treated.
Risks of radiotherapy
TE Schultheiss and L Clifton Stephens reviewed the serious complication of radiation-induced myelopathy in September 1992 (Schultheiss and Clifton Stevens BJR 1992; 65(777): 737-753).
Image source: Schultheiss and Clifton Stevens BJR 1992; 65(777): 737-753
In October AWM Lee and others (Lee, Law. Ng, Chan, Poon, Foo, O, Tung, Cheung and Ho BJR 1992; 65(778): 918-928) reviewed the long-term complications of megavoltage treatment for nasopharyngeal carcinoma (1976-1985). As they say “To achieve the highest cure rate with the lowest morbidity is undoubtedly the ideal goal of every oncologist. This is especially difficult in the treatment of nasopharyngeal carcinoma ………. The balance risk of lethal local failure and that of fatal treatment complications poses a constant dilemma.”
The same group described the local control of nasopharyngeal carcinoma in June 1993 (Lee, Law, Foo, Poon, Chan, O, Tung, Cheung, Thaw, and Hoet 1993; 66,(786): 528-536).