Time, dose and fractionation in radiotherapy
In 1978 JF Fowler from Mount Vernon Hospital reviewed the current state and future possibilities of radiotherapy in his Presidential Address (Fowler BJR 1979; 52(610): 523-535). By the end of the 1970s there had been a rapid application of knowledge gained in the laboratory into clinical practice. In the 1970s there were trials in hyperbaric oxygen, neutron therapy and hypoxic-cell radiosentisers. Major advances were being made in radiotherapy, chemotherapy and the combination of both with surgery.
The concept of the nominal standard dose (NSD) had been first devised by Frank Ellis in 1965 and he returned to the subject in February 1971 (Ellis BJR 1971; 44(518); 101-108) following criticisms by WE Liversage (Liversage BJR 1971; 44(518): 91-100). The assumption was that the normal tissue tolerance was the limiting factor in the treatment of tumours. Frank Ellis had been a member of the ICRU. In July 1973 GC Orton and Frank Ellis presented a simplification of the use of the NSD concept by introducing time, dose and fractionation factors (Orton and Ellis BJR 1973; 46(547): 529-537).
Image source: Orton and Ellis BJR 1973; 46(547): 529-537
The 1972 Silvanus Thompson Memorial Lecture was given by LF Lamerton (Lamerton BJR 1972; 45(531): 161-170) on the important topic of cell proliferation and the differential responses of normal and malignant tissues. His particular hope was that chemotherapy would be able to treat early metastatic disease.
The chemotherapy of cancers had advanced by the end of the 1970s and the topic was reviewed in October 1978 by ES Newlands who was a medical oncologist from Charing Cross Hospital (Newlands BJR 1978; 51(610); 756-770).The author believed that since the majority of cancer patients died from metastatic disease that the major therapeutic advances would now come from better systemic therapy. By 1978 there were some 30 to 40 anti-cancer agents available for clinical use and the numbers continue to grow.
Mary Catterall and others from the Fast Neutron Clinic at the Hammersmith Hospital investigated the clinical effect of fast neutron treatment in August 1971 (Catterall, Rogers, Thomlinson and Field BJR 1971; 44(524): 603-611). Fast neutrons had first been used in treatment in the early 1940s but had been abandoned because of late damage to normal tissues. The BIR had held a symposium in 1963 (Fowler, Morgan and Wood BJR 1963; 36(422); 77-80) and it was believed that the main advantage fast neutrons is the reduced oxygen enhancement effect which enabled the anoxic tumour cells to be killed more readily than normal tissues. In a ‘Radiology Now’ in March 1976 Mary Catterall gave her views on fast neutrons (Catterall BJR 1976; 49(579): 203-205). W Duncan from Edinburgh gave his ‘current thoughts’ on fast neutron therapy in his Mackenzie Davidson Memorial Lecture of 1977 (Duncan BJR 1978; 51(612): 943-952). Many of the patients in the early studies of fast neutrons had advanced tumours however he reported that in some studies the patients treated with fast neutrons had a higher number of serious complications compared to the photon treated group.
Other agents for therapy were discussed in the pages of the BJR. JE Coggle and others from St Bartholomew’s Hospital looked at 70 MeV π-mesons (Coggle, Gordon, Lindop, Shewelll and Mill BJR 1976; 49(578): 161-165) and EJ Hall and H Rossi from New York looked at californium-252 (252Cf) (Hall and Rossi BJR 1975; 48(574): 777-790), which allowed neutron treatment in interstitial and intracavity applications. The use of electrons in mycosis fungoides was described by PC Williams and others from Manchester in April 1979 (Williams, Hunter and Jackson BJR 1979; 52(616): 302-307) and in skin tumours by Elizabeth Grosch and HE Lambert from Mount Vernon Hospital in July 1979 (Grosch and Lambert BJR 1979; 52(618): 472-477).
An important article in four parts was published in the September 1978 BJR comparing the various heavy particles that may be used in therapy. Heavy particles are used because of a desire to minimise the effects on surrounding tissues whilst giving a high dose to the tumour. This is accomplished because of the Bragg peak effect of heavy particles and the well-defined range. There is also a wish to increase the biological effect on tumour cells compared to the normal cells. The four articles covered depth dose distributions (Raju, Amols, Dicello, Howard, Koehler and Samthers BJR 1978; 51(609): 699-703), cell survival verses depth (Raju, Bain, Carpenter, Cox and Robertson BJR 1978; 51(609): 704-711), oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) (Raju, Amols, Bain, Carpenter, Cox and Robertson BJR 1978; 51(609): 712-719) and acute and late reactions (Raju and Carpenter BJR 1978; 51(609): 720-727). There is still a considerable interest in the use of heavy particles and research and development continues.
Image source: Raju, Bain, Carpenter, Cox and Robertson BJR 1978; 51(609): 704-711
In December 1977 DD Loshek and others from Glasgow wrote an interesting account of the interaction of hyperthermia and radiation (Loshek, Orr and Solomonides BJR 1977; 50(600): 893-901). Hyperthermia causes and increased sensitivity to radiation and radiation causes an increased sensitivity to hyperthermia. Following initial experimentation they developed a mathematical model of this interaction.
Hyperbaric oxygen and radiotherapy
A number of papers were presented at the Annual Congress of the BIR in 1977 presenting the results of the Medical Research Council’s (MRC) trials of hyperbaric oxygen in radiotherapy of the head and neck, uterine cervix, bladder and bronchus. A number of papers appeared the November 1978 introduced by Sir Brian Windeyer (Windeyer BJR 1978: 51(611): 875). Patients had been treated for the previous 20 years and the MRC group had been established for 15 years. There followed papers on hyperbaric oxygen in bladder cancer (Cade, McEwan, Dische et al BJR 1978; 51(611): 876-878) and cervical cancer (Watson, Hainan, Dische, Watson, Halnan, Wiernik, Perrins and Sutherland BJR 1978; 51(611): 879-887). There was a final discussion by S Dische from Mount Vernon Hospital (Dische BJR 1978; 51(611): 888-894). Dische concluded that the trials had shown improvement for patients with head and neck and cervical cancer and that the trials had yielded much data of general relevance to radiotherapy. Dische had found no benefit of hyperbaric oxygen in the treatment of bladder cancer in 1973 (Dische BJR 1973; 46(541): 13-17) and cervical cancer in 1974 (Dische BJR 1974; 47(554): 99-107).
Techniques continue to improve and the first therapy paper for 1970 is an account of automatic source placements for Cathetron treatments for the treatment of uterine tumours by D H Twiss and A L Bradshaw (Twiss and Bradshaw BJR 1970; 43(505): 48-53). These techniques had previously been described in the BJR by Charles Joslin and co-workers (Joslin, Liversage and Ramsey BJR 1969; 42(494): 108-112), (O’Connell, Joslin, Howard, Ramsey and Liversage BJR 1967; 40(480): 882-887), (Liversage, Martin-Smith and Ramsey BJR 1967; 40(480): 887-894) & (Joslin, O’Connell and Howard BJR 1967; 40(480): 895-904). The Cathetron had been designed to produce the same dose distribution as the Manchester radium technique. In April 1972 Charles Joslin and others from Velindre Hospital in Cardiff described their treatment of 144 patients and their results compared favourably with those of conventional radiotherapy (Joslin, Smith and Mallik BJR 1972; 45(532(: 257-270). In July 1978 AV Santhamma and JR Das from Bombay examined the dosimetry of Cathetron applicators and compared them to the conventional Manchester loading (Santhamma and Das BJR 1978; 51(607): 507-514).
Image source: Santhamma and Das BJR 1978; 51(607): 507-514
In February 1975 JJ Davy and others from the Royal Free Hospital (Davy, Johnson, Redford and Williams BJR 1975; 48(566): 122-130) gave a detailed account of the principles and applications of the tracking technique using an automated cobalt teletherapy unit. Their technique utilises a moving table and arcing techniques to shape the irradiated volume and so match the tumour volume in three dimensions.
Robert Morrison from the Hammersmith Hospital reviewed laryngeal radiotherapy in July 1971 (Morrison BJR 1971; 44(523): 489-504). Morrison felt that laryngeal cancer was one of the most rewarding tumours for the radiotherapist to treat. In August 1971 M Lederman from the Royal Marsden Hospital published a long study of cancer of the larynx looking at the natural history in relation to treatment (Lederman BJR 1971; 44(524): 569-578) and with MA Whall the technique of treatment (Lederman and Whall BJR 1971; 44(524): 578-589). There is an interesting review of the history of the treatment of laryngeal tumours. The BIR fractionation study on the treatment of the larynx and pharynx continued to publish progress reports (Ellis, Bleehan, Brindle, Brown, Churchill-Davidson, Davidson, Finney, Fowler, Hadden, Hainan, Haybittle, Howard, Mahy, Monypenny, O'Connell, Phillips, Sambrook, Shanks, Sicher, Skeggs, Stewart, Tudway and Wiernik BJR 1971; 44(519): 211-213).
Computers in radiotherapy
Computers were increasingly used in radiotherapy in the 1970s. In November 1971 RE Bentley and J Milan from the Royal Marsden Hospital described the successful use of a digital computer for radiotherapy treatment planning (Bentley and Milan BJR 1971; 44(527): 826-833). In September 1975 RO Kornelsen and MEJ Young from Vancouver (Kornelsen and Young BJR 1975; 48(573): 739-748) wrote on empirical equations for the representation of depth dose data for computerised treatment planning. In the preparation of radiation treatment plans by computer it is necessary to provide information from which depth doses can be obtained. The paper considered pre-measured standard fields. In October 1975 DG Jameson from the Middlesex Hospital described the preparation of the data for interstitial and intracavity dose calculation using interactive and graphic computer techniques (Jameson BJR 1975; 48(574): 827-831). RG Dale was using a computer to calculate the dose distributions of superficial gold-198 implants and made a comparison to the data derived from the Paterson-Parker rules (Dale BJR 1976; 49(582): 533-539). By 1977 AT Redpath and others from Edinburgh had a comprehensive radiotherapy planning system developed on a small computer (Redpath, Vickery and Duncan BJR 1977; 50(589): 51-57) and LM Rosenstein were using computers to optimise source loading in cervical intracavity applicators (Rosenstein BJR 1977; 50(590):119-122). Also in 1977 ME Rosenbloom and others from the Royal Marsden Hospital were monitoring their linear accelerator (Rosenbloom, Killick and Bentley BJR 1977; 50(597): 637-644) with a computer hoping to assess and prevent mistakes and to assist in record keeping.
By 1978 a commercially available dedicated computer treatment planning system (TPS) was described by RG Dale from Charing Cross Hospital (Dale BJR 1978; 51(608): 613-621). The method involved the mathematical generation of the isodose curves and only a limited amount of data retrieval was required. The compute only had a 32K memory.
Image source: Redpath, Vickery and Duncan BJR 1977; 50(589): 51-57