3-D beams need unambiguous names ??A. BAILLIE ANDC. L~pomrn angles with maximum values of 90” (or better yet 45”) for intuitive ease of use. These desires are mutually incompatible. The choice of option 1 means that the desires b, d and e are not met; this is the least satisfactory option. The choice of option 2 means that desire d is not fulfilled for patients not lying prone or supine. It also implies that the pole should follow any small rotations in patient position. We propose that option 3 be used and that desire e be denied for patients not lying prone or supine. Specifically, the pole shall always be defined by the axis about which the couch rotates. This pole, and lines along the length and across the width of the couch, shall each be labelled by the closest anatomical axis of the patient. All angles shall be quoted from the closest axis using the polar coordinate system with the pole defined above. The axes shall be given in order of the size of their components in a ray along the central axis of the beam (or perpendicular to the section). In cases where angles are 45”, Anterior/Posterior shall have precedence, followed by Left/Right, and then by Superior/Inferior. Similarly, coronal shall precede sagittal, which shall in turn precede transverse sections. This proposal makes it trivial to establish the couch and gantry angles for a treatment regardless of patient position. The difficulty is that a beam described as A 30 L 20 I for a sitting patient will be slightly different from one labelled A 30 L 20 I for a patient lying supine. We argue that this is not clinically relevant since the patient’s anatomy will have also deformed substantially in this case, and no exactly equivalent beam could be found in any case; any complete description of a radiological examination must include the patient position. PETERDICKOF COLINLADYKA Allan Blair Memorial Clinic Saskatchewan Cancer Foundation 4101 Dewdney Avenue Regina, Saskatchewan S4T 7Tl Canada 1. Ballie, A.; Lapointe, C. 3-D beams need unambiguous 3-d names. hit. J. Radiat. Oncol. Biol. Phys. 2l:OOOOXlOOO; 1991. 2. Goitein, M. Oblique sections need 3-D names also. Int. J. Radiat. Gncol. Biol. Phys. 19:797-798; 1990. 3. Sailer, S. L.; Bourland, J. D.; Rosenman, J. G.; Sherouse, G. W.; Chaney, E. L.; Tepper, J. E. 3-D beams need 3-D names. Int. J. Radiat. Oncol. Biol. Phys. 19:797-798; 1990.
THE USE OF INTRAOPERATIVE TRANSABDOMINAL ULTRASOUND IN GYNECOLOGIC BRACWTHERAPY To the Editor: A relative indication for interstitial implantation in gynecologic brachy-therapy is cervical stenosis in the patient with squamous cell carcinoma of the cervix. We have recently treated such a patient with Stage II B squamous cell carcinoma of the cervix. The patient received 4500 cGy in 25 fractions using a 15MV linear accelerator. She was taken to the operating room 2 weeks later and a sound was unable to be passed. An interstitial implantation was then performed. To ensure that the needles passed are through the cervix into the uterus with good trajectory, it is possible to use digital examination of the recmm and stay parallel to the axis of the anterior rectal wall. We investigated the use of intra-operative transabdominal ultra-sound in this particular case. In Figure 1 the image of the uterus and cervix are well dileanated. Bright signals representing the interstitial needles are seen to pass through the cervix into the lower uterine segment. We found that the use of intraoperative transabdominal ultrasound aids in confirming needle placement in this circumstance. STEPHEN RUSH RI~AG~TTESMAN JOHNLOVECCHIO Divisions of Radiation Oncology, Uhrasonography, and Division of Gynecologic Oncology, North Shore University Hospital Manhasset, NY 11030
1107
EXACT CALCULATION OF ISODOSES WITH THE LEKSELL GAMMA UNIT To the Editor: We would like to thank the authors (John Flickinger, M.D. et al.) for their comprehensive paper on Treatment Volume Shaping With Selected Beam Blocking Using the Leksell Gamma Unit, which was published in Vol. 19, ~8.783-789 of your journal. The authors found that there were significant differences in the lo%, 30%, and 90% isodoses generated by the dose planning computer and obtained by film dosimetry, respectively. They appear to be unaware of the fact that the treatment planning system that is used with the Leksell Gamma Unit incorporates a function which allows exact calculations if necessary. The exact calculation should be performed when the 14 mm and 18 mm collimeter helmets are extensively plugged. For the 8 mm and 4 mm helmets the exact calculations are unnecessary and only prolong the total time required for planning. The limitation of the computerized planning system of the Leksell Gamma Unit, pointed out by the authors, is not due to the algorithm used for the dose calculation, but rather to the hardware used. With new hardware, which we understand is under development, the calculation times will be significantly reduced and it will be practical to do exact calculations more often or even routinely. SHUNSUKE KAWAM(~TO, M.D. Department of Neurosurgery University of Tokyo Hospital 7-3-l. Hongo, Bunkyo-Ku Tokyo- 113, Japan
RESPONSE TO KAWAMOTO To the Editor: Dr. Kawamoto was quite correct in pointing out that the exact calculation mode of the gamma unit treatment planning system was not used in the isodoses presented in our article on treatment volume shaping with selective beam blocking. In our experience, the isodoses calculated using the rapid “cut and modify” approximation appear to be adequate for daily treatment. The disadvantage of the exact calculation mode is that it takes approximately 20 min per isocenter. As a precaution, we have routinely repeated isodose calculations with the exact calculation mode whenever extensive plugging is used, but we have found no significant differences in the shape of isodose curves. When the computer isodose distributions from Figure 3 in our article were recalculated with both the “cut and modify” and exact calculation modes, all the isodoses were completely superimposable with the exception of some insignificant differences in the 90% isodose contour. The differences between the computer generated isodoses and the film dosimetry remain to be resolved. JOHNC. FLICKWGER, M.D. ANNH. M~rtz ANDREW WU, PH.D. Department of Radiation Oncology University of Pittsburgh School of Medicine 230 Lothrop Street Pittsburgh, PA 15213 1. Flickinger, J. C.; Maitz, A. M.; Kalend, A.; Lunsford, L. D.; Wu, A. Treatment volume shaping with selective beam blocking using the Leksell gamma unit. Int. J. Radiat. Oncol. Biol. Phys. 19:783-789; 1990.
ELECTRON BEAM IRRADIATION OF CONJUNCTIVAL LYMPHOMAS To the Editor: We appreciated (“en connaisseurs”) the article recently published in your journal by Dunbar and colleagues, reporting on the Boston experience of irradiation in conjunctival lymphomas (1). We share with this group the same treatment philosophy and the same clinical experience, with a similar number of treated patients (2).
1108
I. J. Radiation Oncology ??Biology 0 Physics
At the Institut Gustave Roussy, as in Boston, we feel that this particular type of lymphoma should be considered apart from the other lymphomas of the orbit. After dosimetric studies in phantoms, we also used a direct anterior electron beam (4 to 6 MeV) which appeared to be the most appropriate method due to the very anterior topography of the lesions. Fourteen patients (and 19 eyes) with conjunctival lymphomas were treated. The technique benefited from a custom-made individual lead mask with an aperture allowing the irradiation of the entire conjunctiva. The way we shielded the lens and cornea was slightly different from the Dunbar’s technique. A small cylindrical lead block was held 1 to 2 cm above the cornea by a thin metallic wire with both ends fixed on each edge of the aperture of the mask, and bridge-shaped over the aperture. The doses ranged from 36 to 53.7 Gy with conventional fractionation, with most patients being given 40 Gy (a dose slightly higher than the dose delivered in the Dunbar’s series). Immediate tolerance was satisfactory; five interruptions were necessary during treatment but irradiation could be completed to the planned doses in all cases. Out of the 19 treated conjunctivas, only 2 relapses were observed. These 2 relapses occurred in the same patient who suffered from a bilateral involvement. It is worth noting that he was the only patient of our series who was given a first part of his irradiation by conventional roentgentherapy. The patient was salvaged by a second-line electron irradiation which delivered a complete dose to both conjunctivas without any significant late sequelae. As for late complications, four patients subsequently developed a cataract but the link with irradiation was questionable. Two patients developed a bilateral cataract, although only one eye had been treated (DUNBAR and colleagues reported a similar case). For the two other patients, cataract pre-existed and worsened in the treated eye. In conclusion, in our hands, as in Boston, this sophisticated electron beam irradiation of conjunctival lymphomas appears to be efficient and well tolerated, since it was able to achieve a control rate of about 1008, along with a very low percentage of late complications.
September 1991, Volume 21, Number 4 purposes of calculation, for example, mean TPOf= 5 days, SD = 1 day; mean Tpt = 10 days, SD = 2 days. From the probability distribution of a normal Gaussian curve, the tumor cell population can be subdivided into histograms with known ranges of Tpot. By comparing the amount of proliferation in each histogram with the dose required to counteract repopulation within the two halves of a conventional radical treatment course [(l) 30 Gy in 15 fractions over 21 days and (2) 60 Gy in 30 fractions over 42 days], the average dose per day required to counteract proliferation can be estimated. This will be given by:
(SJ”= 1.
1 T P(h)e 0.693 Tp, (h)
c
where S, is surviving fraction after 2 Gy, n = number of fractions to counteract proliferation, P(h) = probability value of each histogram, T = overall time, Tpt (h) = mean TpI value for each histogram. For calculations, 9 histograms extending from 3.6 standard deviations above and below the mean Tpot value were used with CL= 0.35, p = 0.035 as in (3). In this way, for Tpot = 5 days (SD = 1 day) an additional dose of 0.4 Gy per day is required over the first 21 days but 0.8 Gy per day is required during the second 21 days. For a mean Tpot of 10 days (SD = 2 days) an average dose 0.2 Gy per day is required initially while 0.3 Gy per day is required during the final 21 days. This effect is seen to be greater for tumors with lower mean T,,, values. These results show that natural selection of more rapidly proliferating clonogens may account for accelerated repopulation, which has considerable implications for the design of radiotherapy schedules. BLEDDYN JONES,M.Sc.,
L. VmJ T. GIFZNSKY E. BRI~T J. M. COSSET
Department of Radiotherapy and Unite INSERM 247f Institut Gustave Roussy, 94805 Villejuif, France 1. Dunbar, S. F.; Linggood, R. M.; Doppke, M. S.; Duby, A.; Wang, C. C. Conjunctival lymphoma: results and treatment with a single anterior field. A lens sparing approach. Int. J. Radiat. Oncol. Biol. Phys. 91249-257; 1990. 2. Vitu, L.; Cosset, J. M.; Briot, E.; Girinsky, T.; Droz, J. P.; Laumonnier, M.; Bloch-Michel, E. I_es lymphomes malins non hodgkiniens de la conjonctive. A propos de 14 cas trait& a 1’Institut Gustave Roussy. Bull. Cancer Radiother. 77:61-68; 1990.
CELL EEPOPULATION
AND OVERALL TREATMENT TIME
To the Editor: The eloquent article by Trott (4) summarized the possible biological mechanisms for the increase in dose per day required to counteract tumor cell proliferation during fractionated radiotherapy. The contribution of reoxygenation was rejected and that of the inflammatory response was suggested as being the causal mechanism for accelerated repopulation. Neither of these mechanisms are necessary to explain the findings of Maciejewski er al. (2) and Withers et al. (6). Natural selection of tumor cells with TPOtvalues below that of the mean tumor Tpot can explain this effect. Reoxygenation and the inflammatory response could theoretically enhance this process. The Tpt values usually quoted are mean values from single biopsies. Estimates of standard deviation values are obtainable from BrdUrd labelling techniques when multiple biopsies are taken (5). Alternatively, Tpof values can be found by Stathmokinetic experiments since Tpot is the reciprocal of the slope of metaphase arrest lines and linear regression analysis yields the 95% confidence limits (7). From a previous study (1) in C,H mammary carcinoma, mean Tpot values with standard deviations of between 14% and 35% of the mean can be obtained. A value of 20% of the mean Tpt can reasonably be taken as the standard deviate for the
F.R.C.R.
MRCRO Clatterbridge Hospital Bebington, Wirral, Merseyside U.K. 1. Jones, B.; Camplejohn, R. S. Stathmokinetic measurement of tumour cell proliferation in relation to vascular proximity. Cell Tissue Kinet. 16:351-355; 1983. 2. Maciejewski, B.; Preuss-Bayer, G.; Trott, K. R. ‘Ihe influence of the number of fractions on overall treatment time on local control and late complication rate in squamous cell carcinoma of the larynx. Int. J. Radiat. Oncol. Biol. Phys. 9:321-328; 1983. 3. Scott, 0. C. A. Mathematical models of repopulation and reoxygenation in radiotherapy. Br. J. Radiol. 63:821-823; 1990. 4. Trott, K. R. Cell repopulation and overall treatment time. Int. J. Radiat. Oncol. Biol. Phys. 19:1071-1075; 1990. 5. Wilson, G. D.; McNally, N. J.; Dische, S.; Saunders, M. I.; Des Rochers, C.; Lewis, A. A.; Bennett, M. H. Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry. Br. J. Cancer 58:423-432; 1988. 6. Withers, H. R.; Taylor, J. M. G.; Maciejewski, B. The hazard of accelerated tumour clonogen repopulation during radiotherapy. Acta Oncol. 27:131-144; 1988. 7. Wright, N. A.; Appleton, D. R. The metaphase arrest technique: a critical review. Cell Tissue Kinet. 13643-663; 1980.
RESPONSE TO “CELL REPOPULATION AND OVERALL TREATMENT TIME” To the Editor: Accelerated repopulation of tumor stem cells is the hypothetical explanation for the observed dependence of local tumor control dose for squamous cell carcinomas on overall treatment time. Since much data on different types of human cancers are unlikely to be precise enough to derive sound conclusions about the mechanism of tumor stem cell repopulation during the course of radiotherapy, such considerations have to be based on experimental data on animal tumors.
THE USE OF INTRAOPERATIVE TRANSABDOMINAL ULTRASOUND IN GYNECOLOGIC BRACWTHERAPY To the Editor: A relative indication for interstitial implantation in gynecologic brachy-therapy is cervical stenosis in the patient with squamous cell carcinoma of the cervix. We have recently treated such a patient with Stage II B squamous cell carcinoma of the cervix. The patient received 4500 cGy in 25 fractions using a 15MV linear accelerator. She was taken to the operating room 2 weeks later and a sound was unable to be passed. An interstitial implantation was then performed. To ensure that the needles passed are through the cervix into the uterus with good trajectory, it is possible to use digital examination of the recmm and stay parallel to the axis of the anterior rectal wall. We investigated the use of intra-operative transabdominal ultra-sound in this particular case. In Figure 1 the image of the uterus and cervix are well dileanated. Bright signals representing the interstitial needles are seen to pass through the cervix into the lower uterine segment. We found that the use of intraoperative transabdominal ultrasound aids in confirming needle placement in this circumstance. STEPHEN RUSH RI~AG~TTESMAN JOHNLOVECCHIO Divisions of Radiation Oncology, Uhrasonography, and Division of Gynecologic Oncology, North Shore University Hospital Manhasset, NY 11030
1107
EXACT CALCULATION OF ISODOSES WITH THE LEKSELL GAMMA UNIT To the Editor: We would like to thank the authors (John Flickinger, M.D. et al.) for their comprehensive paper on Treatment Volume Shaping With Selected Beam Blocking Using the Leksell Gamma Unit, which was published in Vol. 19, ~8.783-789 of your journal. The authors found that there were significant differences in the lo%, 30%, and 90% isodoses generated by the dose planning computer and obtained by film dosimetry, respectively. They appear to be unaware of the fact that the treatment planning system that is used with the Leksell Gamma Unit incorporates a function which allows exact calculations if necessary. The exact calculation should be performed when the 14 mm and 18 mm collimeter helmets are extensively plugged. For the 8 mm and 4 mm helmets the exact calculations are unnecessary and only prolong the total time required for planning. The limitation of the computerized planning system of the Leksell Gamma Unit, pointed out by the authors, is not due to the algorithm used for the dose calculation, but rather to the hardware used. With new hardware, which we understand is under development, the calculation times will be significantly reduced and it will be practical to do exact calculations more often or even routinely. SHUNSUKE KAWAM(~TO, M.D. Department of Neurosurgery University of Tokyo Hospital 7-3-l. Hongo, Bunkyo-Ku Tokyo- 113, Japan
RESPONSE TO KAWAMOTO To the Editor: Dr. Kawamoto was quite correct in pointing out that the exact calculation mode of the gamma unit treatment planning system was not used in the isodoses presented in our article on treatment volume shaping with selective beam blocking. In our experience, the isodoses calculated using the rapid “cut and modify” approximation appear to be adequate for daily treatment. The disadvantage of the exact calculation mode is that it takes approximately 20 min per isocenter. As a precaution, we have routinely repeated isodose calculations with the exact calculation mode whenever extensive plugging is used, but we have found no significant differences in the shape of isodose curves. When the computer isodose distributions from Figure 3 in our article were recalculated with both the “cut and modify” and exact calculation modes, all the isodoses were completely superimposable with the exception of some insignificant differences in the 90% isodose contour. The differences between the computer generated isodoses and the film dosimetry remain to be resolved. JOHNC. FLICKWGER, M.D. ANNH. M~rtz ANDREW WU, PH.D. Department of Radiation Oncology University of Pittsburgh School of Medicine 230 Lothrop Street Pittsburgh, PA 15213 1. Flickinger, J. C.; Maitz, A. M.; Kalend, A.; Lunsford, L. D.; Wu, A. Treatment volume shaping with selective beam blocking using the Leksell gamma unit. Int. J. Radiat. Oncol. Biol. Phys. 19:783-789; 1990.
ELECTRON BEAM IRRADIATION OF CONJUNCTIVAL LYMPHOMAS To the Editor: We appreciated (“en connaisseurs”) the article recently published in your journal by Dunbar and colleagues, reporting on the Boston experience of irradiation in conjunctival lymphomas (1). We share with this group the same treatment philosophy and the same clinical experience, with a similar number of treated patients (2).
1108
I. J. Radiation Oncology ??Biology 0 Physics
At the Institut Gustave Roussy, as in Boston, we feel that this particular type of lymphoma should be considered apart from the other lymphomas of the orbit. After dosimetric studies in phantoms, we also used a direct anterior electron beam (4 to 6 MeV) which appeared to be the most appropriate method due to the very anterior topography of the lesions. Fourteen patients (and 19 eyes) with conjunctival lymphomas were treated. The technique benefited from a custom-made individual lead mask with an aperture allowing the irradiation of the entire conjunctiva. The way we shielded the lens and cornea was slightly different from the Dunbar’s technique. A small cylindrical lead block was held 1 to 2 cm above the cornea by a thin metallic wire with both ends fixed on each edge of the aperture of the mask, and bridge-shaped over the aperture. The doses ranged from 36 to 53.7 Gy with conventional fractionation, with most patients being given 40 Gy (a dose slightly higher than the dose delivered in the Dunbar’s series). Immediate tolerance was satisfactory; five interruptions were necessary during treatment but irradiation could be completed to the planned doses in all cases. Out of the 19 treated conjunctivas, only 2 relapses were observed. These 2 relapses occurred in the same patient who suffered from a bilateral involvement. It is worth noting that he was the only patient of our series who was given a first part of his irradiation by conventional roentgentherapy. The patient was salvaged by a second-line electron irradiation which delivered a complete dose to both conjunctivas without any significant late sequelae. As for late complications, four patients subsequently developed a cataract but the link with irradiation was questionable. Two patients developed a bilateral cataract, although only one eye had been treated (DUNBAR and colleagues reported a similar case). For the two other patients, cataract pre-existed and worsened in the treated eye. In conclusion, in our hands, as in Boston, this sophisticated electron beam irradiation of conjunctival lymphomas appears to be efficient and well tolerated, since it was able to achieve a control rate of about 1008, along with a very low percentage of late complications.
September 1991, Volume 21, Number 4 purposes of calculation, for example, mean TPOf= 5 days, SD = 1 day; mean Tpt = 10 days, SD = 2 days. From the probability distribution of a normal Gaussian curve, the tumor cell population can be subdivided into histograms with known ranges of Tpot. By comparing the amount of proliferation in each histogram with the dose required to counteract repopulation within the two halves of a conventional radical treatment course [(l) 30 Gy in 15 fractions over 21 days and (2) 60 Gy in 30 fractions over 42 days], the average dose per day required to counteract proliferation can be estimated. This will be given by:
(SJ”= 1.
1 T P(h)e 0.693 Tp, (h)
c
where S, is surviving fraction after 2 Gy, n = number of fractions to counteract proliferation, P(h) = probability value of each histogram, T = overall time, Tpt (h) = mean TpI value for each histogram. For calculations, 9 histograms extending from 3.6 standard deviations above and below the mean Tpot value were used with CL= 0.35, p = 0.035 as in (3). In this way, for Tpot = 5 days (SD = 1 day) an additional dose of 0.4 Gy per day is required over the first 21 days but 0.8 Gy per day is required during the second 21 days. For a mean Tpot of 10 days (SD = 2 days) an average dose 0.2 Gy per day is required initially while 0.3 Gy per day is required during the final 21 days. This effect is seen to be greater for tumors with lower mean T,,, values. These results show that natural selection of more rapidly proliferating clonogens may account for accelerated repopulation, which has considerable implications for the design of radiotherapy schedules. BLEDDYN JONES,M.Sc.,
L. VmJ T. GIFZNSKY E. BRI~T J. M. COSSET
Department of Radiotherapy and Unite INSERM 247f Institut Gustave Roussy, 94805 Villejuif, France 1. Dunbar, S. F.; Linggood, R. M.; Doppke, M. S.; Duby, A.; Wang, C. C. Conjunctival lymphoma: results and treatment with a single anterior field. A lens sparing approach. Int. J. Radiat. Oncol. Biol. Phys. 91249-257; 1990. 2. Vitu, L.; Cosset, J. M.; Briot, E.; Girinsky, T.; Droz, J. P.; Laumonnier, M.; Bloch-Michel, E. I_es lymphomes malins non hodgkiniens de la conjonctive. A propos de 14 cas trait& a 1’Institut Gustave Roussy. Bull. Cancer Radiother. 77:61-68; 1990.
CELL EEPOPULATION
AND OVERALL TREATMENT TIME
To the Editor: The eloquent article by Trott (4) summarized the possible biological mechanisms for the increase in dose per day required to counteract tumor cell proliferation during fractionated radiotherapy. The contribution of reoxygenation was rejected and that of the inflammatory response was suggested as being the causal mechanism for accelerated repopulation. Neither of these mechanisms are necessary to explain the findings of Maciejewski er al. (2) and Withers et al. (6). Natural selection of tumor cells with TPOtvalues below that of the mean tumor Tpot can explain this effect. Reoxygenation and the inflammatory response could theoretically enhance this process. The Tpt values usually quoted are mean values from single biopsies. Estimates of standard deviation values are obtainable from BrdUrd labelling techniques when multiple biopsies are taken (5). Alternatively, Tpof values can be found by Stathmokinetic experiments since Tpot is the reciprocal of the slope of metaphase arrest lines and linear regression analysis yields the 95% confidence limits (7). From a previous study (1) in C,H mammary carcinoma, mean Tpot values with standard deviations of between 14% and 35% of the mean can be obtained. A value of 20% of the mean Tpt can reasonably be taken as the standard deviate for the
F.R.C.R.
MRCRO Clatterbridge Hospital Bebington, Wirral, Merseyside U.K. 1. Jones, B.; Camplejohn, R. S. Stathmokinetic measurement of tumour cell proliferation in relation to vascular proximity. Cell Tissue Kinet. 16:351-355; 1983. 2. Maciejewski, B.; Preuss-Bayer, G.; Trott, K. R. ‘Ihe influence of the number of fractions on overall treatment time on local control and late complication rate in squamous cell carcinoma of the larynx. Int. J. Radiat. Oncol. Biol. Phys. 9:321-328; 1983. 3. Scott, 0. C. A. Mathematical models of repopulation and reoxygenation in radiotherapy. Br. J. Radiol. 63:821-823; 1990. 4. Trott, K. R. Cell repopulation and overall treatment time. Int. J. Radiat. Oncol. Biol. Phys. 19:1071-1075; 1990. 5. Wilson, G. D.; McNally, N. J.; Dische, S.; Saunders, M. I.; Des Rochers, C.; Lewis, A. A.; Bennett, M. H. Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry. Br. J. Cancer 58:423-432; 1988. 6. Withers, H. R.; Taylor, J. M. G.; Maciejewski, B. The hazard of accelerated tumour clonogen repopulation during radiotherapy. Acta Oncol. 27:131-144; 1988. 7. Wright, N. A.; Appleton, D. R. The metaphase arrest technique: a critical review. Cell Tissue Kinet. 13643-663; 1980.
RESPONSE TO “CELL REPOPULATION AND OVERALL TREATMENT TIME” To the Editor: Accelerated repopulation of tumor stem cells is the hypothetical explanation for the observed dependence of local tumor control dose for squamous cell carcinomas on overall treatment time. Since much data on different types of human cancers are unlikely to be precise enough to derive sound conclusions about the mechanism of tumor stem cell repopulation during the course of radiotherapy, such considerations have to be based on experimental data on animal tumors.
