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68 oral: Meta-Analysis of Survival Curves of 3 Radiotherapy Modalities on Biochemical Control and Overall Survival for the Treatment of Prostate Cancer; a Systematic Review
S 24
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Proffered paper Brachytherapy Complementary to External Beam Radiation 68 oral META-ANALYSIS OF SURVIVAL CURVES OF 3 RADIOTHERAPY MODALITIES ON BIOCHEMICAL CONTROL AND OVERALL SURVIVAL FOR THE TREATMENT OF PROSTATE CANCER; A SYSTEMATIC REVIEW B. Pieters1 , D. de Back1 , C. Koning1 , A. Zwinderman2 1 ACADEMIC M EDICAL C ENTER, Department of Radiation Oncology, Amsterdam, Netherlands 2 ACADEMIC M EDICAL C ENTER, Department of Clinical Epidemiology Biostatistics, Amsterdam, Netherlands Purpose: For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be performed by dose escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or highdose rate (HDR) brachytherapy (EBHDR). Differences in outcome between the modalities were assessed by a systematic review. Materials: A systematic search in electronic databases was performed resulting in 40 articles to be used. Data was extracted on biochemical control and overall survival (OS) at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. The average survival curve per treatment modality was estimated by linear meta-regression of the log-minus-log transformed survival points on logtransformed time weighted with the inverse of the squared standard errors of the log-minus-log transformed survival points. In a multivariable regression model Hazard Ratio’s (HR) with 95% confidence intervals (95% CI) were estimated, adjusting for several covariates such as median age, PSA value, Gleason score, clinical T stage, use of hormonal therapy, and year of publication. Results: The majority of studies have used the 1997 ASTRO Consensus Panel definition of biochemical failure to define a biochemical failure (n = 28), however other criteria were also often used. Of the 40 studies 31 reported on biochemical control and 18 on overall survival. The HR for biochemical free survival was 1.40 (95% CI 1.31 to 1.51) for EBRT relative to that of EBHDR and 1.37 (95% CI 1.26 to 1.49) for EBSeeds relative to that of EBHDR, respectively.The HR for OS was 1.50 (95% CI 1.29 to 1.73) for EBRT relative to that of EBHDR, and 2.33 (95% CI 2.04 to 2.66) for EBSeeds relative to that EBHDR, respectively.
S ATURDAY, M AY 16, 2009 PROSTATE CANCER G. Morton1 , D. Loblaw1 , R. Sankreacha2 , A. Deabreu3 , L. Zhang4 , P. Cheung1 , C. Danjoux1 , E. Szumacher1 , E. Vigneault5 , C. Springer6 1 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Radiation Oncology, Toronto, Ontario, Canada 2 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Medical Physics in Radiation Oncology, Toronto, Ontario, Canada 3 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Clinical Epidemiology Biostatistics, Toronto, Ontario, Canada 4 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Biostatistics, Toronto, Ontario, Canada 5 C ENTRE DE RECHERCHE DE L’H ÔTEL -D IEU DE Q UÉBEC DU CHUQ, Department of Radiation Oncology, Québec, Canada 6 W INDSOR R EGIONAL C ANCER C TRE, Department of Radiation Oncology, Windsor, Ontario, Canada Purpose: High dose rate brachytherapy (HDR) for prostate cancer is commonly delivered in 2 or more fractions combined with external beam radiotherapy (EBRT) over 4 to 5 weeks. A single HDR fraction of 15 Gy combined with an EBRT dose of 37.5 Gy in 15 fractions is calculated to be biologically equivalent to 20 Gy HDR in 2 fractions combined with 45 Gy EBRT in 25 fractions. The purpose is to compare short and medium term outcomes of these two fractionation protocols. Materials: Two prospective sequential clinical trials are compared. Eligible patients had intermediate risk prostate cancer (Stage 1 or 2, with either Gleason 6 and PSA of 10-20 ng/ml, or Gleason 7 and PSA < 20 ng/ml). Androgen deprivation was not allowed and prostate volume was < 60 cc. The single fraction (SF) and conventional fraction (CF) groups were well matched for median age (67 vs. 66 yrs), median PSA (7.7 vs. 7.6), stage and baseline symptoms. The SF group had more Gleason 7 (93% vs. 82%) and smaller median prostate volume (32 vs. 39 cc). The 125 SF patients received 15 Gy HDR as a single fraction followed 2 weeks later by 37.5 Gy in 15 fractions over 3 weeks; the 60 CF patients received 20 Gy HDR in 2 fractions followed by 45 Gy in 25 fractions over 5 weeks. HDR was prescribed as a minimal prostate dose; EBRT was delivered to prostate and base of seminal vesicles. Toxicity was assessed prospectively using CTCAE v3 and the International Prostate Symptoms Score (IPSS). Health related quality of life was measured using the Expanded Prostate Index Composite (EPIC). Patients were monitored with PSA and repeat biopsy at 2 years. Median follow-up was 14 months and > 2 years, respectively. Results: SF patients had less acute grade 3 urinary toxicity (1.6% vs. 20%, p=.0005), with a similar incidence of acute grade 2 urinary (60% vs. 55%) and acute grade 2 rectal (6% vs. 11%) toxicity. Grade 2 late urinary toxicity occurred in 40% of SF and 20% of CF at some point (p=.03), but with a lower incidence of Grade 3 late toxicity (0 vs. 7%). Grade 2 late rectal toxicity occurred in 8% and 7%, respectively, with no Grade 3. SF and CF patients both experienced an increase in mean IPSS at 1 month from 6 to 13 and 7 to 13, respectively, but with more rapid return to baseline for SF patients (3 months vs. 6 months). Urinary and bowel EPIC scores were 5-10% lower than baseline at 1 and 2 years, with no difference between treatment groups. The greatest impact was on sexual function scores which decreased by 30% and 35%, respectively at 12 months. Median PSA decreased rapidly in both treatment groups to 1.8 ng/ml at 3 months and 1.1 ng/ml at 6 months, with no difference in median PSA between groups out to 2 years. Prostate biopsy at 2 years showed cancer cells in 11/49 CF patients and 0/17 SF patients (p=.09). PSA failure has occurred in 3/60 CF patients and no SF patient. Conclusions: Single fraction 15 Gy with hypofractionated EBRT is a well tolerated treatment regimen and compares very favourably in the short and medium term with patients treated on a more conventional regimen. 70 oral
Conclusions: The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer. The superior outcome of EBHDR can be explained by the higher dose delivered with this modality. Not all studies used the same criteria for biochemical recurrence, reason why the results must be interpreted with caution. More studies reported on biochemical control making this analysis more robust than on overall survival. Because of these uncertainties the result of this metaanalysis must be confirmed by randomized trials. 69 oral A COMPARISON OF SINGLE FRACTION 15 GY HIGH DOSE-RATE BRACHYTHERAPY BOOST WITH FRACTIONATED BOOST IN
CLINICAL OUTCOME OF INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY + EXTERNAL BEAM RADIOTHERAPY (EBRT) FOR EARLY STAGE PROSTATE CANCER S. Aluwini1 , P. van Rooij1 , P. Jansen1 , J. Praag1 , C. bangma2 , W. Kirkels2 1
E RASMUS M EDICAL C ENTER R OTTERDAM, Department of Radiation Oncology, Rotterdam, Netherlands E RASMUS M EDICAL C ENTER R OTTERDAM, Department of Urology, Rotterdam, Netherlands
2
Purpose: To report the clinical outcome, early and late complications in 264 patients with early stage prostate cancer treated with external beam radiotherapy (EBRT), and high-dose-rate brachytherapy in Rotterdam, the Netherlands. Materials: From February 2000 till August 2007, 264 patients underwent HDR brachytherapy in combination with EBRT as a treatment for their early stage prostate cancer (stage ≤ T2b, Gleason score (GS) ≤ 7, PSA ≤ 15 ng/ml). HDR brachytherapy was performed using ultrasound based implantation (according to IJROBP 1998: 41:3: 525-533), and CT based planning using the PLATO planning system and an 192Ir- microSelectron (according to R&O 2004: 73; 73-77). The total dose was 18 Gy/3 fractions within 24 hours. Conformal EBRT started 2 weeks later and was delivered in 25 fractions of
P ROFFERED PAPER
Proffered paper Brachytherapy Complementary to External Beam Radiation 68 oral META-ANALYSIS OF SURVIVAL CURVES OF 3 RADIOTHERAPY MODALITIES ON BIOCHEMICAL CONTROL AND OVERALL SURVIVAL FOR THE TREATMENT OF PROSTATE CANCER; A SYSTEMATIC REVIEW B. Pieters1 , D. de Back1 , C. Koning1 , A. Zwinderman2 1 ACADEMIC M EDICAL C ENTER, Department of Radiation Oncology, Amsterdam, Netherlands 2 ACADEMIC M EDICAL C ENTER, Department of Clinical Epidemiology Biostatistics, Amsterdam, Netherlands Purpose: For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be performed by dose escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or highdose rate (HDR) brachytherapy (EBHDR). Differences in outcome between the modalities were assessed by a systematic review. Materials: A systematic search in electronic databases was performed resulting in 40 articles to be used. Data was extracted on biochemical control and overall survival (OS) at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. The average survival curve per treatment modality was estimated by linear meta-regression of the log-minus-log transformed survival points on logtransformed time weighted with the inverse of the squared standard errors of the log-minus-log transformed survival points. In a multivariable regression model Hazard Ratio’s (HR) with 95% confidence intervals (95% CI) were estimated, adjusting for several covariates such as median age, PSA value, Gleason score, clinical T stage, use of hormonal therapy, and year of publication. Results: The majority of studies have used the 1997 ASTRO Consensus Panel definition of biochemical failure to define a biochemical failure (n = 28), however other criteria were also often used. Of the 40 studies 31 reported on biochemical control and 18 on overall survival. The HR for biochemical free survival was 1.40 (95% CI 1.31 to 1.51) for EBRT relative to that of EBHDR and 1.37 (95% CI 1.26 to 1.49) for EBSeeds relative to that of EBHDR, respectively.The HR for OS was 1.50 (95% CI 1.29 to 1.73) for EBRT relative to that of EBHDR, and 2.33 (95% CI 2.04 to 2.66) for EBSeeds relative to that EBHDR, respectively.
S ATURDAY, M AY 16, 2009 PROSTATE CANCER G. Morton1 , D. Loblaw1 , R. Sankreacha2 , A. Deabreu3 , L. Zhang4 , P. Cheung1 , C. Danjoux1 , E. Szumacher1 , E. Vigneault5 , C. Springer6 1 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Radiation Oncology, Toronto, Ontario, Canada 2 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Medical Physics in Radiation Oncology, Toronto, Ontario, Canada 3 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Department of Clinical Epidemiology Biostatistics, Toronto, Ontario, Canada 4 O DETTE C ANCER C ENTRE , S UNNYBROOK H EALTH S CIENCES C ENTRE, Biostatistics, Toronto, Ontario, Canada 5 C ENTRE DE RECHERCHE DE L’H ÔTEL -D IEU DE Q UÉBEC DU CHUQ, Department of Radiation Oncology, Québec, Canada 6 W INDSOR R EGIONAL C ANCER C TRE, Department of Radiation Oncology, Windsor, Ontario, Canada Purpose: High dose rate brachytherapy (HDR) for prostate cancer is commonly delivered in 2 or more fractions combined with external beam radiotherapy (EBRT) over 4 to 5 weeks. A single HDR fraction of 15 Gy combined with an EBRT dose of 37.5 Gy in 15 fractions is calculated to be biologically equivalent to 20 Gy HDR in 2 fractions combined with 45 Gy EBRT in 25 fractions. The purpose is to compare short and medium term outcomes of these two fractionation protocols. Materials: Two prospective sequential clinical trials are compared. Eligible patients had intermediate risk prostate cancer (Stage 1 or 2, with either Gleason 6 and PSA of 10-20 ng/ml, or Gleason 7 and PSA < 20 ng/ml). Androgen deprivation was not allowed and prostate volume was < 60 cc. The single fraction (SF) and conventional fraction (CF) groups were well matched for median age (67 vs. 66 yrs), median PSA (7.7 vs. 7.6), stage and baseline symptoms. The SF group had more Gleason 7 (93% vs. 82%) and smaller median prostate volume (32 vs. 39 cc). The 125 SF patients received 15 Gy HDR as a single fraction followed 2 weeks later by 37.5 Gy in 15 fractions over 3 weeks; the 60 CF patients received 20 Gy HDR in 2 fractions followed by 45 Gy in 25 fractions over 5 weeks. HDR was prescribed as a minimal prostate dose; EBRT was delivered to prostate and base of seminal vesicles. Toxicity was assessed prospectively using CTCAE v3 and the International Prostate Symptoms Score (IPSS). Health related quality of life was measured using the Expanded Prostate Index Composite (EPIC). Patients were monitored with PSA and repeat biopsy at 2 years. Median follow-up was 14 months and > 2 years, respectively. Results: SF patients had less acute grade 3 urinary toxicity (1.6% vs. 20%, p=.0005), with a similar incidence of acute grade 2 urinary (60% vs. 55%) and acute grade 2 rectal (6% vs. 11%) toxicity. Grade 2 late urinary toxicity occurred in 40% of SF and 20% of CF at some point (p=.03), but with a lower incidence of Grade 3 late toxicity (0 vs. 7%). Grade 2 late rectal toxicity occurred in 8% and 7%, respectively, with no Grade 3. SF and CF patients both experienced an increase in mean IPSS at 1 month from 6 to 13 and 7 to 13, respectively, but with more rapid return to baseline for SF patients (3 months vs. 6 months). Urinary and bowel EPIC scores were 5-10% lower than baseline at 1 and 2 years, with no difference between treatment groups. The greatest impact was on sexual function scores which decreased by 30% and 35%, respectively at 12 months. Median PSA decreased rapidly in both treatment groups to 1.8 ng/ml at 3 months and 1.1 ng/ml at 6 months, with no difference in median PSA between groups out to 2 years. Prostate biopsy at 2 years showed cancer cells in 11/49 CF patients and 0/17 SF patients (p=.09). PSA failure has occurred in 3/60 CF patients and no SF patient. Conclusions: Single fraction 15 Gy with hypofractionated EBRT is a well tolerated treatment regimen and compares very favourably in the short and medium term with patients treated on a more conventional regimen. 70 oral
Conclusions: The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer. The superior outcome of EBHDR can be explained by the higher dose delivered with this modality. Not all studies used the same criteria for biochemical recurrence, reason why the results must be interpreted with caution. More studies reported on biochemical control making this analysis more robust than on overall survival. Because of these uncertainties the result of this metaanalysis must be confirmed by randomized trials. 69 oral A COMPARISON OF SINGLE FRACTION 15 GY HIGH DOSE-RATE BRACHYTHERAPY BOOST WITH FRACTIONATED BOOST IN
CLINICAL OUTCOME OF INTERSTITIAL HIGH DOSE RATE (HDR) BRACHYTHERAPY + EXTERNAL BEAM RADIOTHERAPY (EBRT) FOR EARLY STAGE PROSTATE CANCER S. Aluwini1 , P. van Rooij1 , P. Jansen1 , J. Praag1 , C. bangma2 , W. Kirkels2 1
E RASMUS M EDICAL C ENTER R OTTERDAM, Department of Radiation Oncology, Rotterdam, Netherlands E RASMUS M EDICAL C ENTER R OTTERDAM, Department of Urology, Rotterdam, Netherlands
2
Purpose: To report the clinical outcome, early and late complications in 264 patients with early stage prostate cancer treated with external beam radiotherapy (EBRT), and high-dose-rate brachytherapy in Rotterdam, the Netherlands. Materials: From February 2000 till August 2007, 264 patients underwent HDR brachytherapy in combination with EBRT as a treatment for their early stage prostate cancer (stage ≤ T2b, Gleason score (GS) ≤ 7, PSA ≤ 15 ng/ml). HDR brachytherapy was performed using ultrasound based implantation (according to IJROBP 1998: 41:3: 525-533), and CT based planning using the PLATO planning system and an 192Ir- microSelectron (according to R&O 2004: 73; 73-77). The total dose was 18 Gy/3 fractions within 24 hours. Conformal EBRT started 2 weeks later and was delivered in 25 fractions of