28 x 1.8 Gy = 50.4 Gy ~ 95.8 Gy 2 x 9 Gy (BT)= 18 Gy ~ 99 Gy
∑ BED 160 Gy (213) ∑ BED 194,8 Gy (295)
IMRT vs. 3D-conformal RT + HDR-BRT
Biologic Effective Dose = f (Repair factor, fractional dose, number of fractions)
Presenter
Presentation Notes
Ein Vergleich der kombinierten Brachytherapie (BT + EBRT) mit der IMRT ist eigentlich nicht möglich. Ein Anhalt bietet die Dosiskalkulation nach dem LQ – Modell. Im theoretischen Vergleich ist die biologisch effektive Dosis einer kombinierten Radiotherapie ( 2 x 9 Gy (BT) + 28 x 1,8Gy = 50,4 Gy (EBRT)) mit einer IMRT (40 x 2Gy = 80Gy) deutlich höher. Insbesondere wenn man ein alpha/Beta Quotient von 1,2 im Sinne eines ausgeprägten Reparaturvermögens der Prostatazellen annimmt.
CTV 1 = CTV = PTV
Dose/Fx (Gy) # Fxs Total D
(Gy) BED
(a/b=1,5) % Dose EQD 2
9.5 2 19 247 57 106
10.5 2 21 275 61 118
11.5 2 23 307 65 131
Athens Consensus
Boost + EBRT 46 Gy at 2 Gy or 45 Gy at 1.8 Gy
>> 160 Gy
[Zelefsky J. Urol 2001, Memorial Sloan Kettering]
Value of external Dose escalation?
Presenter
Presentation Notes
J Urol. 2001 Sep;166(3):876-81. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, Reuter VE, Venkatraman ES, Leibel SA. Source Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Erratum in Abstract PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. MATERIALS AND METHODS: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio
[ Zelefsky et al. IJROBP 2008, Memorial Sloan Kettering ]
GI
GU IMRT
3D–70,2Gy
3D–75,6Gy
3D–75,6Gy 3D–70,2Gy IMRT
Incidence of late Rectal and Urinary Toxicities after 3D-conformal RT and IMRT for localized Prostate Cancer
Presenter
Presentation Notes
Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1124-9. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Zelefsky MJ, Levin EJ, Hunt M, Yamada Y, Shippy AM, Jackson A, Amols HI. Source Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. [email protected] Abstract PURPOSE: To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer. METHODS AND MATERIALS: Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS: The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively. CONCLUSIONS: Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.
cine-MR over 7 min -> up to 1.2 cm displacement
Intrafractional Movement
Repositioning issue in EBRT ?
[ Padhani et al. IJROBP 1999]
Presenter
Presentation Notes
Int J Radiat Oncol Biol Phys. 1999 Jun 1;44(3):525-33. Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI. Padhani AR, Khoo VS, Suckling J, Husband JE, Leach MO, Dearnaley DP. Source CRC Clinical Magnetic Resonance Research Group, The Institute of Cancer Research and The Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom. Abstract PURPOSE: To evaluate the dynamic interrelationship between rectal distension and rectal movements, and to determine the effect of rectal movement on the position of the prostatic gland using cine magnetic resonance imaging (MRI). METHODS AND MATERIALS: Fifty-five patients with biopsy-proven or suspected prostate cancer were examined in the axial plane using repeated spoiled gradient-echo sequences every 10 seconds for 7 minutes. Twenty-four patients received bowel relaxants before imaging. Images were analyzed for the degree of rectal distension, for the incidence, magnitude, and number of rectal and prostate movements. RESULTS: Rectal movements were seen in 28 (51%) patients overall, in 10 (42%) of those receiving bowel relaxants and in 18 (58%) not receiving bowel relaxants. The incidence of rectal movements correlated with the degree of rectal distension (p = 0.0005), but the magnitude of rectal movements did not correlate with the degree of rectal distension. Eighty-six rectal movements resulting in 33 anterior-posterior (AP) prostate movements were seen. The magnitude of rectal movements correlated well with degree of prostate movements (p < 0.001). Prostate movements in the AP direction were seen in 16 (29%) patients, and in 9 (16%) patients the movement was greater than 5 mm. The median prostate AP displacement was anterior by 4.2 (-5 to +14 mm). CONCLUSIONS: Cine MRI is able to demonstrate near real time rectal and associated prostate movements. Rectal movements are related to rectal distension and result in significant displacements of the prostate gland over a time period similar to that used for daily fractionated radiotherapy treatments. Delivery of radiotherapy needs to take into account these organ movements.
Electromagnetic System (Calypso)
[ Bittner et al IJROBP 2010 ] [ Langen et al IJROBP 2008 ]
Presenter
Presentation Notes
Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1084-90. Epub 2008 Feb 14. Observations on real-time prostate gland motion using electromagnetic tracking. Langen KM, Willoughby TR, Meeks SL, Santhanam A, Cunningham A, Levine L, Kupelian PA. Source Department of Radiation Oncology, M. D. Anderson Cancer Center Orlando, Orlando, FL 32806, USA. [email protected] Abstract PURPOSE: To quantify and describe the real-time movement of the prostate gland in a large data set of patients treated with radiotherapy. METHODS AND MATERIALS: The Calypso four-dimensional localization system was used for target localization in 17 patients, with electromagnetic markers implanted in the prostate of each patient. We analyzed a total of 550 continuous tracking sessions. The fraction of time that the prostate was displaced by >3, >5, >7, and >10 mm was calculated for each session and patient. The frequencies of displacements after initial patient positioning were analyzed over time. RESULTS: Averaged over all patients, the prostate was displaced >3 and >5 mm for 13.6% and 3.3% of the total treatment time, respectively. For individual patients, the corresponding maximal values were 36.2% and 10.9%. For individual fractions, the corresponding maximal values were 98.7% and 98.6%. Displacements >3 mm were observed at 5 min after initial alignment in about one-eighth of the observations, and increased to one-quarter by 10 min. For individual patients, the maximal value of the displacements >3 mm at 5 and 10 min after initial positioning was 43% and 75%, respectively. CONCLUSION: On average, the prostate was displaced by >3 mm and >5 mm approximately 14% and 3% of the time, respectively. For individual patients, these values were up to three times greater. After the initial positioning, the likelihood of displacement of the prostate gland increased with elapsed time. This highlights the importance of initiating treatment shortly after initially positioning the patient.
Arguments for HDR - Brachytherapy
Dose application in short time high biologic effectivity [ Martinez et al. IJROBP 2000 ]
Intensity modulation and high conformality with Real Time Dosimetry + Inverse Planning [ Edmundson et al. IJROBP 1993 ]
In comparison to EBRT no relevant interfractional or intrafractional movement [ Martinez et al. IJROBP 2001] [ Deutsch et al. Brachytherapy 2010]
[ Stromberg et al. IJROBP 1995 ]
Presenter
Presentation Notes
Martinez AA, Kestin LL, Stromberg JS, Gonzalez JA, Wallace M, Gustafson GS, Edmundson GK, Spencer W, Vicini FA. Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial. Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):343-52. Edmundson GK, Rizzo NR, Teahan M, Brabbins D, Vicini FA, Martinez A. Concurrent treatment planning for outpatient high dose rate prostate template implants. Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1215-23. Deutsch I, Zelefsky MJ, Zhang Z, Mo Q, Zaider M, Cohen G, Cahlon O, Yamada Y. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy. 2010 Oct-Dec;9(4):313-8. Epub 2010 Aug 4. Stromberg J, Martinez A, Gonzalez J, Edmundson G, Ohanian N, Vicini F, Hollander J, Gustafson G, Spencer W, Yan D, et al. Ultrasound-guided high dose rate conformal brachytherapy boost in prostate cancer: treatment description and preliminary results of a phase I/II clinical trial. Int J Radiat Oncol Biol Phys. 1995 Aug 30;33(1):161-71.
Case #2
HDR-Boost to EBRT “Evolution of Dose Constraints”
Kini VR et al. Use of three-dimensional radiation therapy planning tools and
intraoperative ultrasound to evaluate high dose rate prostate brachytherapy implants. Int J Radiat Oncol Biol Phys 1999; 43:571-8.
Martinez AA et al. Conformal high-dose-rate brachytherapy as monotherapy for the
treatment of favorable stage prostate cancer: a feasibility report. Int J Radiat Oncol Biol Phys 2001; 49:61-9.
Hsu IC et al. Comparison of inverse planning simulated annealing and geometrical
optimization for prostate high-dose-rate brachytherapy. Brachytherapy 2004; 3:147-52.
