1975, British Journal of Radiology, 48, 872 Correspondence THE EDITOR—SIR, ARE NEGATIVE PIMESONS REALLY NECESSARY?
There are three reasons for developing the use of negative pimesons and heavy ions for the treatment of cancer. These are: (1) The high RBE of these radiations at a depth, in the region of the peak dose. (2) The low OER. (3) The improved dose distribution in a phantom. Unless the desired dose distribution in the patient can be made to coincide with the position of the cancer the advantages of the first two of these reasons is lost. Indeed, it is possible that errors in positioning could result in a high RBE seriously damaging a sensitive organ such as the kidney. On the other hand it must be assumed that the facilities and expertise available in connection with such costly installations will be such as to ensure avoiding vital and sensitive normal structures even if the exact position of the malignant process cannot be known. Some disadvantages of such installations are: (1) The high cost resulting in too few centres to deal with the patients requiring treatment. (2) Deterioration of dose distribution with increasing area of single beams. (3) Diminished dose-rate if all the beams in a multiple beam machine cannot be used {e.g. in the Stanford multiple beam machine). (4) The difficulties always inherent in radiation therapy, of knowing the precise position and size of the malignant process. (5) The production of other particles which can reach and damage other tissues. On the other hand, the use of 4TT curietherapy with suitable radioactive sources and afterloading techniques has much to recommend it. (The term 4TT is more logical than brachytherapy as a distinction from beam therapy.) 1. The dose distribution can be limited to the region of the target volume with a rapid fall-off outside it. 2. The shape of the treated volume can be varied, e.g. a curved plane on the chest wall or an ellipsoid in the prostate gland. 3. The radiopaque active sources used for treatment can be used as markers for the position of the tumour so that supplementary external radiation can be used. 4. Such sources can be inserted at a surgical operation. What is needed to exploit the use of active sources is more ingenuity in devising methods of applying them so that the geometry is good, and in producing the necessary isotopes in suitable form and quantity. For temporary implants they should be available for afterloading at a suitable time after an operation. For permanent implants they should be available immediately. In addition the training of radiation therapists to think in terms of such treatment and of surgeons to become awake to the possible advantages is most desirable. It may be that the local application of heat could be facilitated by the presence in microwave beams of the radioactive sources and their metal jackets. If primary tumours in difficult situations such as the lung, pancreas and prostate can be dealt with consistently well by local methods, the further cooperation of chemical oncologists and immunological oncologists in dealing with systemic metastases may have greater success. AT: curietherapy can be used more widely, less expensively and more immediately than negative pimesons. It would seem to be worthwhile to put a larger slice of the financial pie into such methods and into the appropriate training than has so far been the case. Yours, etc., F.
Memorial Hospital for Cancer and Allied Diseases, New York, 10021, U.S.A.
ELLIS.
THE EDITOR—SIR, A NEW SCREEN/FILM COMBINATION APPLICABLE TO MAMMOGRAPHY
We have read with interest the letter by G. M. Ardran, W. A. Langmead and H. E. Crooks in your March issue discussing a new screen/film combination. In this they mention a reduction in radiation exposure in mammography obtained by using Trimax XD film in conjunction with an Alpha 8 back screen and compared it with Medichrome film and a high definition calcium tungstate back screen. Recently Agfa-Gevaert Ltd. have provided us with new rare earth intensifying screens which we have used as a vacuum packed back screen with Medichrome film for mammography. The screen has the advantage of emitting blue light and thus normal blue-sensitive black and white and Medichrome film can be used and handled under conventional darkroom conditions. Tests with a standard Kodak Pathe mammogram phantom showed that a 50 per cent reduction of exposure time could be achieved when compared with Medichrome and an Ilford high definition screen. Photomicrographs of the 50 /xm mesh on this phantom showed that resolution and sharpness were identical, and similar to that of Cronex "Lo dose" film. White fused bauxilite (white fused alumina) particles embedded in paraffin wax of a mean size of 145 fim could be identified readily on all these films with a hand lens. (On an industrial film, Structurix D4 used without an intensifying screen, 105 yu,m particles were identifiable.) This system has been used on 50 patients and we have found that mammograms taken with Medichrome and the rare earth screen are indistinguishable from those taken with an Ilford high definition screen and the radiation exposure is cut by a half. The exposure conditions are 100 mAs, 30 kVp and 60 cm FFD; the skin dose is in the range of 0-15-0-3 rad per exposure, measured by thermoluminescent dosimetry. Yours etc., J. L. PRICE, P. D. BUTLER.
Royal Surrey County Hospital, Guildford.
THE EDITOR—SIR, ENHANCED KILLING OF HYPOXIC TUMOUR CELLS BY HYPERTHERMIA
There is abundant evidence that cancer cells grown in vivo or in vitro are sensitive to elevated temperature (Cavaliere, 1967; Overgaard and Overgaard, 1972). Clinically, Coley (1893), near the beginning of this century, achieved a considerable success in the regression of tumours by inducing high temperatures in cancer patients with bacterial toxins. Since then, the literature contains numerous cases of the arrest or total disappearance of cancer after prolonged fever (Cavaliere, 1967). Recently, renewed interest in the combined use of hyperthermia and radiotherapy or chemotherapy has been generated at both the laboratory and the clinical level (Suit and Shwayder, 1974). In the case of radiotherapy, a single most important radiobiological concept relevant to therapy is the fact that large solid tumours contain a population of hypoxic cells which are still clonogenic. These cells constitute the most radioresistant fraction, and require two to three times more radiation dose compared with well-oxygenated cells. It is generally thought that this radioresistant tumour cell fraction results in failure of local tumour control by radiation therapy. Various means have been employed to overcome this problem: hyperbaric oxygen chambers have been used to increase the oxygenation of tumours and high LET radiations are being explored because of their relative independence from an oxygen effect on cell killing.
872
There are three reasons for developing the use of negative pimesons and heavy ions for the treatment of cancer. These are: (1) The high RBE of these radiations at a depth, in the region of the peak dose. (2) The low OER. (3) The improved dose distribution in a phantom. Unless the desired dose distribution in the patient can be made to coincide with the position of the cancer the advantages of the first two of these reasons is lost. Indeed, it is possible that errors in positioning could result in a high RBE seriously damaging a sensitive organ such as the kidney. On the other hand it must be assumed that the facilities and expertise available in connection with such costly installations will be such as to ensure avoiding vital and sensitive normal structures even if the exact position of the malignant process cannot be known. Some disadvantages of such installations are: (1) The high cost resulting in too few centres to deal with the patients requiring treatment. (2) Deterioration of dose distribution with increasing area of single beams. (3) Diminished dose-rate if all the beams in a multiple beam machine cannot be used {e.g. in the Stanford multiple beam machine). (4) The difficulties always inherent in radiation therapy, of knowing the precise position and size of the malignant process. (5) The production of other particles which can reach and damage other tissues. On the other hand, the use of 4TT curietherapy with suitable radioactive sources and afterloading techniques has much to recommend it. (The term 4TT is more logical than brachytherapy as a distinction from beam therapy.) 1. The dose distribution can be limited to the region of the target volume with a rapid fall-off outside it. 2. The shape of the treated volume can be varied, e.g. a curved plane on the chest wall or an ellipsoid in the prostate gland. 3. The radiopaque active sources used for treatment can be used as markers for the position of the tumour so that supplementary external radiation can be used. 4. Such sources can be inserted at a surgical operation. What is needed to exploit the use of active sources is more ingenuity in devising methods of applying them so that the geometry is good, and in producing the necessary isotopes in suitable form and quantity. For temporary implants they should be available for afterloading at a suitable time after an operation. For permanent implants they should be available immediately. In addition the training of radiation therapists to think in terms of such treatment and of surgeons to become awake to the possible advantages is most desirable. It may be that the local application of heat could be facilitated by the presence in microwave beams of the radioactive sources and their metal jackets. If primary tumours in difficult situations such as the lung, pancreas and prostate can be dealt with consistently well by local methods, the further cooperation of chemical oncologists and immunological oncologists in dealing with systemic metastases may have greater success. AT: curietherapy can be used more widely, less expensively and more immediately than negative pimesons. It would seem to be worthwhile to put a larger slice of the financial pie into such methods and into the appropriate training than has so far been the case. Yours, etc., F.
Memorial Hospital for Cancer and Allied Diseases, New York, 10021, U.S.A.
ELLIS.
THE EDITOR—SIR, A NEW SCREEN/FILM COMBINATION APPLICABLE TO MAMMOGRAPHY
We have read with interest the letter by G. M. Ardran, W. A. Langmead and H. E. Crooks in your March issue discussing a new screen/film combination. In this they mention a reduction in radiation exposure in mammography obtained by using Trimax XD film in conjunction with an Alpha 8 back screen and compared it with Medichrome film and a high definition calcium tungstate back screen. Recently Agfa-Gevaert Ltd. have provided us with new rare earth intensifying screens which we have used as a vacuum packed back screen with Medichrome film for mammography. The screen has the advantage of emitting blue light and thus normal blue-sensitive black and white and Medichrome film can be used and handled under conventional darkroom conditions. Tests with a standard Kodak Pathe mammogram phantom showed that a 50 per cent reduction of exposure time could be achieved when compared with Medichrome and an Ilford high definition screen. Photomicrographs of the 50 /xm mesh on this phantom showed that resolution and sharpness were identical, and similar to that of Cronex "Lo dose" film. White fused bauxilite (white fused alumina) particles embedded in paraffin wax of a mean size of 145 fim could be identified readily on all these films with a hand lens. (On an industrial film, Structurix D4 used without an intensifying screen, 105 yu,m particles were identifiable.) This system has been used on 50 patients and we have found that mammograms taken with Medichrome and the rare earth screen are indistinguishable from those taken with an Ilford high definition screen and the radiation exposure is cut by a half. The exposure conditions are 100 mAs, 30 kVp and 60 cm FFD; the skin dose is in the range of 0-15-0-3 rad per exposure, measured by thermoluminescent dosimetry. Yours etc., J. L. PRICE, P. D. BUTLER.
Royal Surrey County Hospital, Guildford.
THE EDITOR—SIR, ENHANCED KILLING OF HYPOXIC TUMOUR CELLS BY HYPERTHERMIA
There is abundant evidence that cancer cells grown in vivo or in vitro are sensitive to elevated temperature (Cavaliere, 1967; Overgaard and Overgaard, 1972). Clinically, Coley (1893), near the beginning of this century, achieved a considerable success in the regression of tumours by inducing high temperatures in cancer patients with bacterial toxins. Since then, the literature contains numerous cases of the arrest or total disappearance of cancer after prolonged fever (Cavaliere, 1967). Recently, renewed interest in the combined use of hyperthermia and radiotherapy or chemotherapy has been generated at both the laboratory and the clinical level (Suit and Shwayder, 1974). In the case of radiotherapy, a single most important radiobiological concept relevant to therapy is the fact that large solid tumours contain a population of hypoxic cells which are still clonogenic. These cells constitute the most radioresistant fraction, and require two to three times more radiation dose compared with well-oxygenated cells. It is generally thought that this radioresistant tumour cell fraction results in failure of local tumour control by radiation therapy. Various means have been employed to overcome this problem: hyperbaric oxygen chambers have been used to increase the oxygenation of tumours and high LET radiations are being explored because of their relative independence from an oxygen effect on cell killing.
872
