- Email: [email protected]
70 oral: Clinical Outcome of Interstitial High Dose Rate (HDR) Brachytherapy + External Beam Radiotherapy (EBRT) for Early Stage Prostate Cancer
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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
S ATURDAY, M AY 16, 2009 1.8Gy to 45 Gy within 5 weeks. Results: Median age of patients was 66 years (range 45-79), 60.7% with stage T1c and 32.7% with stage T2a, 6% had GS of 7, 94% had GS 6 or less. Median iPSA was 5.8 (range 0.3-14 ng/ml). Median number of needles was 19 (12-29), median prostate volume was 30 cc (11-93), the PTV V100 was 95.7%, median (63-99.7), urethra V120 was 0.0cc (0.0-0.2), rectum V80 was 0.1cc (0.0-1.2). In 25 patients a simple bladder perforation (9%) was recorded, and 5 patients had a urethral perforation (2%). Median follow-up was 51 months (range 12-105).The incidence of grade 2 and 3 acute urinary toxicity evaluated by urinary RTOG toxicity scale was 19% and 3% respectively. After 5 years this percentage was 7% and 2% respectively. Acute grade 2 bowel toxicity was 6%, and grade 3 was 3%. Mild late bowel toxicity normalized after 5 years from 2% to 0%. Fecal incontinence and proctitis needing medical treatment after 5 years was registered in 2.5% and 1.5% of patients respectively. Four patients experienced a PSA progression according to the ASTRO definition and 7 patients according to the Phoenix definition. A proven clinical progression (bone metastases) was documented in only 2 patients (0.07%). Five years DSS and OS were 100% and 92% respectively. Conclusions: Interstitial High Dose Rate (HDR) Brachytherapy + External Beam Radiotherapy (EBRT) are well tolerated, with a low incidence of late complications, and showing a favorable oncological outcome after 8 years of follow-up. 71 oral ANALYSIS OF PSA BOUNCE IN SUBJECTS TREATED WITH HDR BRACHYTHERAPY BOOST COMPARED TO PERMANENT IMPLANT BRACHYTHERAPY OR EBRT S. Ozard1 , L. Flett2 1 W INDSOR R EGIONAL C ANCER C TRE, Medical Physics, Windsor, Ontario, Canada 2 M C M ASTER U NIVERSITY, Medical Physics, Hamilton, Canada Purpose: To investigate the nature and incidence of a transient rise (bounce) in prostate specific antigen (PSA) levels after prostate cancer radiotherapy with high-dose rate (HDR) brachytherapy boost combined with external beam radiation therapy (EBRT); to compare the HDR results to data for permanent radioactive seed implant (LDR) or EBRT alone. Materials: This study is a retrospective analysis of serial PSA measurements for a total of 341 study subjects with at least 3 years of physician follow-up after treatment. Statistical analysis was performed to determine if there was an association between PSA bounce and the following variables: prostate volume, pre and post-treatment PSA, and biochemical failure. Bounce was defined as a transient rise of at least 0.4ng/mL above the nadir followed by a decline back to or below the nadir. Biochemical failure was defined as a rise of 2ng/mL or higher from the nadir. Results: Median follow-up was 4.5 years. Sample size for the HDR group was 75. For the HDR group the bounce frequency was 8%, the median bounce height was 1ng/mL, the median time to onset of bounce was 12.4 months, and the median bounce duration was 13.2 months. Statistical analysis using pooled data from all three treatment modalities revealed that subjects who experienced a PSA bounce were more likely to be younger (p=0.0004), have a smaller prostate volume (p=0.001), a lower pre-treatment PSA (p=0.06), and a higher 6-month post-treatment PSA level (p<0.0001). For the 6-month post-treatment PSA a cutoff was defined at 0.9ng/mL; subjects above the cutoff had a 36% chance of PSA bounce, subjects below the cutoff had a 6% chance of a PSA bounce. Biochemical relapse free survival was lower for the LDR subjects who experienced bounce compared to the non-bounce subjects (p=0.003); the same outcome was found for the EBRT subjects (p<0.0001). Conclusions: PSA bounces of 2ng/mL or higher were seen in 1.3% of the HDR subjects. From the pooled data for the three treatment modalities the median onset of PSA bounce was 19 months (range 7 to 35 months), while biochemical failure usually occurred later (median 37 months, range 8 to 87 months). 72 oral SEVERE LATE EFFECTS AFTER RADIOTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER; COMPARISON OF TWO BRACHYTHERAPY SCHEDULES AND IMPACT OF DOSE DELIVERED PER WEEK T. P. Hellebust1 , D. R. Olsen2 1 R IKSHOSPITALET-R ADIUMHOSPITALET HF, Department of Medical Physics, Oslo, Norway 2 R IKSHOSPITALET-R ADIUMHOSPITALET HF, Department of Radiation Biology, Oslo, Norway Purpose: To compare severe late effects (> grade 2) for two groups of cervical cancer patients treated with the same external beam radiotherapy and two different high-dose-rate intracavitary brachytherapy (ICBT) regimes and to investigate the influence of dose delivered each week. Materials: 120 patients the ICBT was delivered with 33.6Gy in 8 fractions to
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point A (HDgroup) and for 119 patients the ICBT was delivered with 29.4Gy in 7 fractions to point A (LDgroup). The cumulative incidence of severe gastrointestinal (GI) and genitourinary (GU) late effects were calculated for both dose groups using Kaplan-Meyer survival analysis. This method was also used to explore if the number of weeks with different dose levels could predict the cumulative incidence of late effects. Results: The actuarial rate of developing severe GI morbidity at 7 years was 10.7% and 8.3% for HDgroup and LDgroup, respectively. The corresponding figures for GU morbidity were 6.6% for the HDgroup and 5.0% for the LDgroup. There was no significant difference between the two groups. The analyses showed that that there was a marginally significant increase in severe GI complications as the number of weeks with physical dose higher than 20Gy increase in the HDgroup (p = 0.047). Conclusions: To establish dose response relationships for late complications 3D imaging and DVH parameters are needed. There were some indications that 20Gy per week is an upper tolerance level when the dose to ICRU rectum point is 81Gy(EQD2-alfa/beta=3). However, further investigations using 3D data are needed. 73 oral MIDLINE BLOCK RESULTS IN AN UNPREDICTABLE DOSE TO TUMOUR AND ORGANS-AT-RISK WHEN USED WITH COMBINED EXTERNAL BEAM RADIOTHERAPY AND BRACHYTHERAPY IN LOCALLY ADVANCED CERVICAL CANCER: RESULTS FROM A 3D MRI BASED DVH ANALYSIS K. Tanderup1 , L. Fenkell2 , S. K. Nielsen1 , M. S. Assenholt1 , C. HaieMeder3 , R. Pötter4 , J. C. Lindegaard1 1 A ARHUS U NIVERSITY H OSPITAL, Department of Oncology, Aarhus C, Denmark 2 P RINCESS M ARGARET H OSPITAL, Department of Radiation Oncology, Toronto, Canada 3 I NSTITUTE G USTAVE R OUSSY, Department of Radiotherapy, Villejuif, France 4 M EDICAL U NIVERSITY OF V IENNA, Department of Radiotherapy, Vienna, Austria Purpose: Midline shielding is often used in the treatment of locally advanced cervical cancer with radiotherapy in attempt to spare midline organs while boosting the pelvic side wall. The purpose of this study was to evaluate the contribution of dose from midline-blocked fields to the D2cc of rectum, sigmoid and bladder and to the D90 and D100 of HR CTV and IR CTV. Materials: 6 patients with locally advanced cervical cancer (IIB-IIIB) treated with definitive concurrent 3D conformal chemoradiotherapy and MRI-guided brachytherapy were analysed. All the cases selected had large and topographically unfavorable tumours at the time of brachytherapy (BT). A conventional radiotherapy schedule was modeled: 45Gy (1.8Gy x 25) 4 field box EBRT, 9 Gy (1.8Gy x 5) parametrial boost (AP-PA fields with midline block), and an intracavitary MRI-guided BT boost of 28Gy (7Gy x 4) using a tandemring applicator. Rectangular midline shields of 3, 4, and 5 cm widths were simulated for each patient by dose planning on the brachytherapy MRI images which were fused with CT in order to obtain Hounsfield units. Dose matrices from MRI-guided BT plans and EBRT midline block plans were volumetrically summed. The D2cc of rectum, sigmoid and bladder and the D90 and D100 of the HR CTV and IR CTV were evaluated. All doses were converted to 2 Gy per fraction equivalent doses (EQD2) and combined with the 4 field box EBRT dose. Intended dose to HR CTV was D90>85Gy and in IR CTV D90>65-70Gy. Results: The table below shows the mean dose contribution from the parametrial boost to OAR’s and target structures. In 4/6 patients the dose to at least one OAR increased by more than 4.5Gy (50% of parametrial boost dose). HR CTV D90 and D100 were increased by less than 4.5Gy in 3/6 and 2/6 patients, respectively. IR CTV D90 and D100 were increased by less than 4.5Gy in 1/6 and 5/6 patients. Without a parametrial boost, the target coverage was compromised with a mean HR CTV D90 of 69Gy [range 58-79Gy] and IR CTV D90 of 56Gy [range 53-64Gy]. Even after a parametrial boost using a 4cm midline block, target coverage remained compromised in all cases, with a mean HR CTV D90 of 74Gy [range 64-82Gy] and IR CTV D90 of 62Gy [range 59-67Gy]. Conclusions: The midline block neither predictably protects OARs nor adds sufficient dose to the HR or IR CTV in large tumours. Midline blocked fields significantly contribute dose to the D2cc of rectum, sigmoid and bladder. In addition, target coverage remains compromised for the HR and IR CTV, despite application of a parametrial boost.
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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
S ATURDAY, M AY 16, 2009 1.8Gy to 45 Gy within 5 weeks. Results: Median age of patients was 66 years (range 45-79), 60.7% with stage T1c and 32.7% with stage T2a, 6% had GS of 7, 94% had GS 6 or less. Median iPSA was 5.8 (range 0.3-14 ng/ml). Median number of needles was 19 (12-29), median prostate volume was 30 cc (11-93), the PTV V100 was 95.7%, median (63-99.7), urethra V120 was 0.0cc (0.0-0.2), rectum V80 was 0.1cc (0.0-1.2). In 25 patients a simple bladder perforation (9%) was recorded, and 5 patients had a urethral perforation (2%). Median follow-up was 51 months (range 12-105).The incidence of grade 2 and 3 acute urinary toxicity evaluated by urinary RTOG toxicity scale was 19% and 3% respectively. After 5 years this percentage was 7% and 2% respectively. Acute grade 2 bowel toxicity was 6%, and grade 3 was 3%. Mild late bowel toxicity normalized after 5 years from 2% to 0%. Fecal incontinence and proctitis needing medical treatment after 5 years was registered in 2.5% and 1.5% of patients respectively. Four patients experienced a PSA progression according to the ASTRO definition and 7 patients according to the Phoenix definition. A proven clinical progression (bone metastases) was documented in only 2 patients (0.07%). Five years DSS and OS were 100% and 92% respectively. Conclusions: Interstitial High Dose Rate (HDR) Brachytherapy + External Beam Radiotherapy (EBRT) are well tolerated, with a low incidence of late complications, and showing a favorable oncological outcome after 8 years of follow-up. 71 oral ANALYSIS OF PSA BOUNCE IN SUBJECTS TREATED WITH HDR BRACHYTHERAPY BOOST COMPARED TO PERMANENT IMPLANT BRACHYTHERAPY OR EBRT S. Ozard1 , L. Flett2 1 W INDSOR R EGIONAL C ANCER C TRE, Medical Physics, Windsor, Ontario, Canada 2 M C M ASTER U NIVERSITY, Medical Physics, Hamilton, Canada Purpose: To investigate the nature and incidence of a transient rise (bounce) in prostate specific antigen (PSA) levels after prostate cancer radiotherapy with high-dose rate (HDR) brachytherapy boost combined with external beam radiation therapy (EBRT); to compare the HDR results to data for permanent radioactive seed implant (LDR) or EBRT alone. Materials: This study is a retrospective analysis of serial PSA measurements for a total of 341 study subjects with at least 3 years of physician follow-up after treatment. Statistical analysis was performed to determine if there was an association between PSA bounce and the following variables: prostate volume, pre and post-treatment PSA, and biochemical failure. Bounce was defined as a transient rise of at least 0.4ng/mL above the nadir followed by a decline back to or below the nadir. Biochemical failure was defined as a rise of 2ng/mL or higher from the nadir. Results: Median follow-up was 4.5 years. Sample size for the HDR group was 75. For the HDR group the bounce frequency was 8%, the median bounce height was 1ng/mL, the median time to onset of bounce was 12.4 months, and the median bounce duration was 13.2 months. Statistical analysis using pooled data from all three treatment modalities revealed that subjects who experienced a PSA bounce were more likely to be younger (p=0.0004), have a smaller prostate volume (p=0.001), a lower pre-treatment PSA (p=0.06), and a higher 6-month post-treatment PSA level (p<0.0001). For the 6-month post-treatment PSA a cutoff was defined at 0.9ng/mL; subjects above the cutoff had a 36% chance of PSA bounce, subjects below the cutoff had a 6% chance of a PSA bounce. Biochemical relapse free survival was lower for the LDR subjects who experienced bounce compared to the non-bounce subjects (p=0.003); the same outcome was found for the EBRT subjects (p<0.0001). Conclusions: PSA bounces of 2ng/mL or higher were seen in 1.3% of the HDR subjects. From the pooled data for the three treatment modalities the median onset of PSA bounce was 19 months (range 7 to 35 months), while biochemical failure usually occurred later (median 37 months, range 8 to 87 months). 72 oral SEVERE LATE EFFECTS AFTER RADIOTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER; COMPARISON OF TWO BRACHYTHERAPY SCHEDULES AND IMPACT OF DOSE DELIVERED PER WEEK T. P. Hellebust1 , D. R. Olsen2 1 R IKSHOSPITALET-R ADIUMHOSPITALET HF, Department of Medical Physics, Oslo, Norway 2 R IKSHOSPITALET-R ADIUMHOSPITALET HF, Department of Radiation Biology, Oslo, Norway Purpose: To compare severe late effects (> grade 2) for two groups of cervical cancer patients treated with the same external beam radiotherapy and two different high-dose-rate intracavitary brachytherapy (ICBT) regimes and to investigate the influence of dose delivered each week. Materials: 120 patients the ICBT was delivered with 33.6Gy in 8 fractions to
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point A (HDgroup) and for 119 patients the ICBT was delivered with 29.4Gy in 7 fractions to point A (LDgroup). The cumulative incidence of severe gastrointestinal (GI) and genitourinary (GU) late effects were calculated for both dose groups using Kaplan-Meyer survival analysis. This method was also used to explore if the number of weeks with different dose levels could predict the cumulative incidence of late effects. Results: The actuarial rate of developing severe GI morbidity at 7 years was 10.7% and 8.3% for HDgroup and LDgroup, respectively. The corresponding figures for GU morbidity were 6.6% for the HDgroup and 5.0% for the LDgroup. There was no significant difference between the two groups. The analyses showed that that there was a marginally significant increase in severe GI complications as the number of weeks with physical dose higher than 20Gy increase in the HDgroup (p = 0.047). Conclusions: To establish dose response relationships for late complications 3D imaging and DVH parameters are needed. There were some indications that 20Gy per week is an upper tolerance level when the dose to ICRU rectum point is 81Gy(EQD2-alfa/beta=3). However, further investigations using 3D data are needed. 73 oral MIDLINE BLOCK RESULTS IN AN UNPREDICTABLE DOSE TO TUMOUR AND ORGANS-AT-RISK WHEN USED WITH COMBINED EXTERNAL BEAM RADIOTHERAPY AND BRACHYTHERAPY IN LOCALLY ADVANCED CERVICAL CANCER: RESULTS FROM A 3D MRI BASED DVH ANALYSIS K. Tanderup1 , L. Fenkell2 , S. K. Nielsen1 , M. S. Assenholt1 , C. HaieMeder3 , R. Pötter4 , J. C. Lindegaard1 1 A ARHUS U NIVERSITY H OSPITAL, Department of Oncology, Aarhus C, Denmark 2 P RINCESS M ARGARET H OSPITAL, Department of Radiation Oncology, Toronto, Canada 3 I NSTITUTE G USTAVE R OUSSY, Department of Radiotherapy, Villejuif, France 4 M EDICAL U NIVERSITY OF V IENNA, Department of Radiotherapy, Vienna, Austria Purpose: Midline shielding is often used in the treatment of locally advanced cervical cancer with radiotherapy in attempt to spare midline organs while boosting the pelvic side wall. The purpose of this study was to evaluate the contribution of dose from midline-blocked fields to the D2cc of rectum, sigmoid and bladder and to the D90 and D100 of HR CTV and IR CTV. Materials: 6 patients with locally advanced cervical cancer (IIB-IIIB) treated with definitive concurrent 3D conformal chemoradiotherapy and MRI-guided brachytherapy were analysed. All the cases selected had large and topographically unfavorable tumours at the time of brachytherapy (BT). A conventional radiotherapy schedule was modeled: 45Gy (1.8Gy x 25) 4 field box EBRT, 9 Gy (1.8Gy x 5) parametrial boost (AP-PA fields with midline block), and an intracavitary MRI-guided BT boost of 28Gy (7Gy x 4) using a tandemring applicator. Rectangular midline shields of 3, 4, and 5 cm widths were simulated for each patient by dose planning on the brachytherapy MRI images which were fused with CT in order to obtain Hounsfield units. Dose matrices from MRI-guided BT plans and EBRT midline block plans were volumetrically summed. The D2cc of rectum, sigmoid and bladder and the D90 and D100 of the HR CTV and IR CTV were evaluated. All doses were converted to 2 Gy per fraction equivalent doses (EQD2) and combined with the 4 field box EBRT dose. Intended dose to HR CTV was D90>85Gy and in IR CTV D90>65-70Gy. Results: The table below shows the mean dose contribution from the parametrial boost to OAR’s and target structures. In 4/6 patients the dose to at least one OAR increased by more than 4.5Gy (50% of parametrial boost dose). HR CTV D90 and D100 were increased by less than 4.5Gy in 3/6 and 2/6 patients, respectively. IR CTV D90 and D100 were increased by less than 4.5Gy in 1/6 and 5/6 patients. Without a parametrial boost, the target coverage was compromised with a mean HR CTV D90 of 69Gy [range 58-79Gy] and IR CTV D90 of 56Gy [range 53-64Gy]. Even after a parametrial boost using a 4cm midline block, target coverage remained compromised in all cases, with a mean HR CTV D90 of 74Gy [range 64-82Gy] and IR CTV D90 of 62Gy [range 59-67Gy]. Conclusions: The midline block neither predictably protects OARs nor adds sufficient dose to the HR or IR CTV in large tumours. Midline blocked fields significantly contribute dose to the D2cc of rectum, sigmoid and bladder. In addition, target coverage remains compromised for the HR and IR CTV, despite application of a parametrial boost.