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173Influence of gap position on the response of the R1H-tumour to fractionated split-course irradiation treatment
$46 170 NATIONAL AUDITING SYSTEM FOR QA IN RADIOTHERAPY IN CZECH REPUBLIC I.Pfidal, T.Kl~Iov~,OacologicalClinic, UnivermtyHospital, Olonmuc J.Novo(~, St~eotacLRad.Ncurosurg.Dept.,Hosp.NsHomolce~Prague H~i~ NationalRad.Pretln~., P ~ C-~.~hRepublic According to a new "Atomic law" m~-ry radio0~'rapy department will be ohliged to ias~l a Quality Assurance programme from I.January 1997. The implmnmtation of QA progmnunes in radiotherapy will be faciliated if appropriate organisation at the counUy level is made respopnsible for : a) providing technical a ~ s ~ c e and co-ordinatinn in the set~ng up of QA programmes and in particular in the ta~'in£ of newly commissioned radio~erspy deparUnen~ b) asccft:~inin,e the adequacy of QA at radiotherapy department level and advising ~ r d i n g ] y , c) developing, adapting and disseminating reconanm~cm, codes of practice, regulations, norms, etc, produced by or endorsed by national organizations, d) ansuring the prov~on of, or access to cafibration facilities, e) providing assistance in the analysis of the results of QA programs in finding means of improving performance, 0 o~rEa"i'~"~ trainingon QA. A system for quality auditing of radiotherapy depemnents from the physical point of view, which is obligatory for all radiotherapy depanmems and which is supervisedby State Office for Nuclear and Radiation Safety (SONS) will be presented. The auditing group ( 10 medical physicim from radimhenpy departments) tice~ed by SONS and based in the National l~i:tton l~-o~ction Institutewillperform at the baginningtwo mains m k s : a) regularpostalTLD auditof all photonand electronbeams withinthe country, and b) in sire measure~ants whe~.ver a new instalation is announced and at regular cbecks (three yesrs period), l.X.vr on the itm~ listed above will be covered also. A mO.hodologyfor checking of basic parameters of therapy units, simulators and treatment planing systems is derived from national recommendations published few years ago. Geographical dislxibution of elemants of the system will be illustrated and preliminaryresultswillbe presented.
172 T H E STANDARD R A D I O B I O L O G I C A L P A R A M E T E R S MIGHT NOT EXPLAIN THE POOR RESPONSE OF GLIOBLASTOMA XENOGRAFTS TO RADIATION
A. Taghian, P. Huang, A. Allam, L. Perez, Y. Boucher, I. Lee, I. Azinovic, M. Duffy, A. DaCosta, K. Held, H. D. Suit Steele Lab, Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, M A 02114 U S A Baekeround: Glioblastoma Multiforme (GBM) is a highly malignant tumor-of the central nervous system with aggressive biological behavior and a fatal clinical outcome. Several radiobiological parameters might contribute to these poor results. Purnose: We investigated eighteen in vivo and in vitro radiobiological parameters of four GBM xonografts and compared the results with four other histological types of human tumor xenografts in nude mice. Methods and Materials: Most of the xenografts retained the individual histological features of their original tumor types. The corresponding cell lines were karyotyped. Four GBM xenografts (U87, HP555, MMCI and HGL21). two squamous cell carcinomas (SCC21 and FaDu), one soft tissue sarcoma (STS26T), and colon cancer (HCTI5) xenografts were used. The tumors were implanted in the hindleg of 5-6 Gy whole body irradiated nude mice. The following parameters were investigated for most of the xenografts: fractionated TCD50 (the dose of radiation which controls 50% of the tumors) using 30 fractions in 15 days. The parameters pO2, radiobiologic hypoxic fraction, IFP (interstitial fluid pressure), Tpot, SF2 (plastic and Courtenay), PE (plating efficiency), Do, GSH, TCDs0 single dose in oxic and hypoxic conditions, the rate of metastasis in SCID mice, VDT (volume doubling time), spontaneous apoptosis, induced apoptosis after 30 and 60 Gy and p53 over-expression. Results: Using the t-test, there was a significantly less spontaneous apoptosis in GBM xenografts when compared with the other histological types. However, no significant difference was found between both groups of xenografts in the remaining biological parameters investigated. Conclusion: These data demonstrate that, with the exception of spontaneous apoptosis, no significant difference was found in seventeen biological parameters between GBM xenografts and the other histological types implanted into the subcutaneous tissue of nude mice. The data suggests that the classical radiobiological parameters cannot explain the poor response of OBM xenografts to radiation. Supported by NCI Grant CA13311 awarded by DHHS.
171 Different impact of time, dose and fractionatioa on local control of two human H&N SCC in nude mice
Cordula Liertz and Michael Banma.,.n Dept. of R,di~tion Therapy,Technical University of Dresden, Germany Background: Only li~e is known about the degree of heteregnneity of the radiation response of tumors of the same entity after modificationx of clinical fractionation schedulcs. Purpose: To adress the question of intertumoral heterogeneity, the impact oftbe number of fractions (12, 30, 60fin 6 w) and overall treaUnant time (30f h 2, 3, 4.5, 6, 10w) on local tumor conUol was evaluated in two human bead and neck squamons cell catcinonm in nude mice. In addition local control after single doses aad recovmy fi'om sublethal radiation damage was studied in vivo. Mato'/a/s and Methods: FaDu-tumors (poorly differentiated, VDT 3.5¢1, T~=l,8-2.5d) and GL-tumors (moderatelyweft differentiated, V D T 9d, T~,=2.4-3.Sd) were transplanted s.c. into NMRI uu/nu mice (4 Gy WBI). Local irradiation (200 kV x-rays, 0.5 Cu) started when the tumors ~120mm3. The experimental emipoint was TCDso at day 120 (FaDu) or day 180 (GL) after end of ueetmt~. The data were evaluated by Direct Analysis according to the (extended) LQ-Modei. Results: Single dose (SD)-TCD~s under clamp hypoxin (el) were 41 Gy [95%C1 38;43] for FaDu and 43 Gy [40;47] for GL, and oJJ3-values detemtined fiom l, 2, 4, 8f,j4d (OER=2.7) were 15 G) [9,24] and 49 [26;122), respectively. TCDso values after 12, 30, 60~6w were constant in FaDe-tumors (63 Cry [55;73]), odl3e~was infinite with the lower 95%CL being 52 Gy. In contrast, in GL-tumors the TCDso increased significantly from 35 Cry [28;44] after 12f to 44 Gy [38;52] after 30f, and 56 Gy [50-64] after 60f. (a/[3w= 3 Cry [0.6-12]). In both tumors a significant time factor was observed when the overall t~ne of irr~di,,tlon with 30f was increased fi'om 2 to 10 weeks. The dose recovered per day was I Gy [0.7;1.3] in FaDu, but only 0.26 C-y [0.05; 0.5]) in GL. Conclusion: Despite of almost identical SD.,-TCD~, and similarly high a/13-values, the impact of time and fractionmion on local oontrol of FaDuand GL-SCC after clinical radiation schedules was markedly different. Supported by the Deutsche Fo~chungsgemeinachaR (Ba 1433)
173 Influence of gap imsition on the response of the R H l . t u m o u r to fractionated split-course irradiation treatment
JORGZIERON,M. OMNIC2YNSK1,H.-P. BEcK-BORNHOLDT Institute of Biophysics and Radiobiology, University of Hamburg, Germany Gaps, either planned or unplanned, are a common feature of clinical radiotherapy. Although there is good evidence for the negative effect of gaps on local turnout control rate, there is available little information about the influence of the position of the gap on treatment outcome. Subcutaneously growing rhabdomyosarcomas R1H of the rat were irr~iated with a fraclionafion schedule by applying five fractions per week over six weeks. This standard treatment was modified by inserting a two week gap either after the first (early gap), the third (cenual gap), or the fifth week Gate gap). In addition, an accelerated ueatmcnt arm with five fractions per week applied over five weeks, was examined for comparison. Turnout response was quantified by determination of local tomour control and net growth delay. TCD37 and corresponding 95% confidence intervals were calculated applying the Maximum-Likelihood method. The positionof the gap had a significant(p=0.018) influence on the TCD~, amounting to 97.5 G y (95%-C.L: 90.9-oo) for the early gap, 104.9 Gy (96.6-113.7)for the centralgap, and 92.5 G y (85.9-98.5),for the late gap. A significantincrease of T C D ~ was observed for all split-course ueatments, compared to the standard schedule, which showed a TCD37 of 83.0 Gy (78.5-91.2). In the accelerated schedule a TCDyl of 75.7 Gy (71.2-82.5) was observed. Comparison of early and lategap resultswith the accelerated schedule show that the five week course was decisive for local mmour control, whereas the dose applied in the short one week course was lost. The growth delay results obtained after a central gap show that tumour response to f~acfiounted ixradiation was identical in both three week courses before and after the gap. Supported by the Deutsche Forschungsgemeinschafl.
172 T H E STANDARD R A D I O B I O L O G I C A L P A R A M E T E R S MIGHT NOT EXPLAIN THE POOR RESPONSE OF GLIOBLASTOMA XENOGRAFTS TO RADIATION
A. Taghian, P. Huang, A. Allam, L. Perez, Y. Boucher, I. Lee, I. Azinovic, M. Duffy, A. DaCosta, K. Held, H. D. Suit Steele Lab, Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, M A 02114 U S A Baekeround: Glioblastoma Multiforme (GBM) is a highly malignant tumor-of the central nervous system with aggressive biological behavior and a fatal clinical outcome. Several radiobiological parameters might contribute to these poor results. Purnose: We investigated eighteen in vivo and in vitro radiobiological parameters of four GBM xonografts and compared the results with four other histological types of human tumor xenografts in nude mice. Methods and Materials: Most of the xenografts retained the individual histological features of their original tumor types. The corresponding cell lines were karyotyped. Four GBM xenografts (U87, HP555, MMCI and HGL21). two squamous cell carcinomas (SCC21 and FaDu), one soft tissue sarcoma (STS26T), and colon cancer (HCTI5) xenografts were used. The tumors were implanted in the hindleg of 5-6 Gy whole body irradiated nude mice. The following parameters were investigated for most of the xenografts: fractionated TCD50 (the dose of radiation which controls 50% of the tumors) using 30 fractions in 15 days. The parameters pO2, radiobiologic hypoxic fraction, IFP (interstitial fluid pressure), Tpot, SF2 (plastic and Courtenay), PE (plating efficiency), Do, GSH, TCDs0 single dose in oxic and hypoxic conditions, the rate of metastasis in SCID mice, VDT (volume doubling time), spontaneous apoptosis, induced apoptosis after 30 and 60 Gy and p53 over-expression. Results: Using the t-test, there was a significantly less spontaneous apoptosis in GBM xenografts when compared with the other histological types. However, no significant difference was found between both groups of xenografts in the remaining biological parameters investigated. Conclusion: These data demonstrate that, with the exception of spontaneous apoptosis, no significant difference was found in seventeen biological parameters between GBM xenografts and the other histological types implanted into the subcutaneous tissue of nude mice. The data suggests that the classical radiobiological parameters cannot explain the poor response of OBM xenografts to radiation. Supported by NCI Grant CA13311 awarded by DHHS.
171 Different impact of time, dose and fractionatioa on local control of two human H&N SCC in nude mice
Cordula Liertz and Michael Banma.,.n Dept. of R,di~tion Therapy,Technical University of Dresden, Germany Background: Only li~e is known about the degree of heteregnneity of the radiation response of tumors of the same entity after modificationx of clinical fractionation schedulcs. Purpose: To adress the question of intertumoral heterogeneity, the impact oftbe number of fractions (12, 30, 60fin 6 w) and overall treaUnant time (30f h 2, 3, 4.5, 6, 10w) on local tumor conUol was evaluated in two human bead and neck squamons cell catcinonm in nude mice. In addition local control after single doses aad recovmy fi'om sublethal radiation damage was studied in vivo. Mato'/a/s and Methods: FaDu-tumors (poorly differentiated, VDT 3.5¢1, T~=l,8-2.5d) and GL-tumors (moderatelyweft differentiated, V D T 9d, T~,=2.4-3.Sd) were transplanted s.c. into NMRI uu/nu mice (4 Gy WBI). Local irradiation (200 kV x-rays, 0.5 Cu) started when the tumors ~120mm3. The experimental emipoint was TCDso at day 120 (FaDu) or day 180 (GL) after end of ueetmt~. The data were evaluated by Direct Analysis according to the (extended) LQ-Modei. Results: Single dose (SD)-TCD~s under clamp hypoxin (el) were 41 Gy [95%C1 38;43] for FaDu and 43 Gy [40;47] for GL, and oJJ3-values detemtined fiom l, 2, 4, 8f,j4d (OER=2.7) were 15 G) [9,24] and 49 [26;122), respectively. TCDso values after 12, 30, 60~6w were constant in FaDe-tumors (63 Cry [55;73]), odl3e~was infinite with the lower 95%CL being 52 Gy. In contrast, in GL-tumors the TCDso increased significantly from 35 Cry [28;44] after 12f to 44 Gy [38;52] after 30f, and 56 Gy [50-64] after 60f. (a/[3w= 3 Cry [0.6-12]). In both tumors a significant time factor was observed when the overall t~ne of irr~di,,tlon with 30f was increased fi'om 2 to 10 weeks. The dose recovered per day was I Gy [0.7;1.3] in FaDu, but only 0.26 C-y [0.05; 0.5]) in GL. Conclusion: Despite of almost identical SD.,-TCD~, and similarly high a/13-values, the impact of time and fractionmion on local oontrol of FaDuand GL-SCC after clinical radiation schedules was markedly different. Supported by the Deutsche Fo~chungsgemeinachaR (Ba 1433)
173 Influence of gap imsition on the response of the R H l . t u m o u r to fractionated split-course irradiation treatment
JORGZIERON,M. OMNIC2YNSK1,H.-P. BEcK-BORNHOLDT Institute of Biophysics and Radiobiology, University of Hamburg, Germany Gaps, either planned or unplanned, are a common feature of clinical radiotherapy. Although there is good evidence for the negative effect of gaps on local turnout control rate, there is available little information about the influence of the position of the gap on treatment outcome. Subcutaneously growing rhabdomyosarcomas R1H of the rat were irr~iated with a fraclionafion schedule by applying five fractions per week over six weeks. This standard treatment was modified by inserting a two week gap either after the first (early gap), the third (cenual gap), or the fifth week Gate gap). In addition, an accelerated ueatmcnt arm with five fractions per week applied over five weeks, was examined for comparison. Turnout response was quantified by determination of local tomour control and net growth delay. TCD37 and corresponding 95% confidence intervals were calculated applying the Maximum-Likelihood method. The positionof the gap had a significant(p=0.018) influence on the TCD~, amounting to 97.5 G y (95%-C.L: 90.9-oo) for the early gap, 104.9 Gy (96.6-113.7)for the centralgap, and 92.5 G y (85.9-98.5),for the late gap. A significantincrease of T C D ~ was observed for all split-course ueatments, compared to the standard schedule, which showed a TCD37 of 83.0 Gy (78.5-91.2). In the accelerated schedule a TCDyl of 75.7 Gy (71.2-82.5) was observed. Comparison of early and lategap resultswith the accelerated schedule show that the five week course was decisive for local mmour control, whereas the dose applied in the short one week course was lost. The growth delay results obtained after a central gap show that tumour response to f~acfiounted ixradiation was identical in both three week courses before and after the gap. Supported by the Deutsche Forschungsgemeinschafl.