An update on NTCP data

Transcription

1 An update on NTCP data Vladimir Semenenko, Ph.D. X. Allen Li, Ph.D. Department of Radiation Oncology Medical College of Wisconsin NCCAAPM 2006 Fall Meeting, October 3, 2006

2 Goal of Radiation Therapy Maximize probability of tumor eradication Minimize probability of injury to surrounding normal tissues

3 Goal of Radiation Therapy Probability of Outcome Tumor Control Probability (TCP) TCP ( NTCP) Normal Tissue Complication Probability (NTCP) Radiation Dose

4 Goal of Radiation Therapy Maximize probability of tumor eradication Deliver sufficient dose to tumor cells Minimize probability of injury to surrounding normal tissues Reduce normal tissue doses to acceptable levels

5 Tissue Tolerance Data Emami et al. IJROBP 2, 09-22, 99 Review of literature and personal experience of the authors 28 critical sites, TD 5/5 and TD 50/5 for one-third, two-thirds thirds and the whole organ Data fit to the Lyman model by Burman et al. (IJROBP 2, 23-35, 35, 99) n, m, TD 50

6 Lyman-Kutcher Kutcher-Burman (LKB) Model Lyman Radiat.. Res. 04, S3-9, 985; Kutcher and Burman IJROBP 6, , 989 t 2 x 2 NTCP = e dx 2π 3 parameters: n, m, TD 50 t D TD eff 50 / = mtd 50 D n n eff = vd i i i n = Deff = Dmean = vd i i i

7 Lyman Model in Clinical Practice Dose-escalation escalation study for intrahepatic cancers; NTCP = 0% (McGinn( et al. JCO 6, , 998) 3D-CRT dose-escalation escalation studies for NSCLC; NTCP 25% (Rozenzweig( et al. Cancer 03, 28-27, 27, 2005) SBRT (3 9-5 Gy/fr); NTCP 20% 4 out of 7 patients had grade -2 2 RP (Song et al. AJCO 28, 59-6, 2005)

8 Project Goal To identify reliable estimates of Lyman model parameters for the purposes of biologically-based based treatment planning

9 Lung Reference n m TD 50 (Gy) Endpoint Fractionation Scheme Lung Burman et al Pneumonitis.8-2 Gy q.d. Martel et al SWOG grade RP.8-2 Gy q.d. Kwa et al SWOG grade 2 RP -2.7 Gy q.d.; normalized to 2 Gy/fr using α/β of 2.5 or 3 Gy Seppenwoolde et al SWOG grade 2 RP SWOG grade 3 RP -2.7 Gy q.d.; normalized to 2 Gy/fr using α/β of 2.5 or 3 Gy Moiseenko et al Symptomatic pneumonitis -2 Gy q.d.; normalized to 2 Gy/fr using α/β of 3 Gy Radiographic and symptomatic pneumonitis

10 Lung Observed RP Rate Graham et al. 999 (Washington U) - RTOG grade >=2 Moiseenko et al (Canada) - RTOG grade >=2 Maximum likelihood fit - no steroids n = m = 0.40 TD50 = 29.5 Gy Observed RP Rate Seppenwoolde et al (Netherlands) - SWOG grade >=2 Willner et al (Germany) - NCI CTC grade >=2 Kim et al (Korea) - RTOG grade >=3 Yorke et al (MSKCC) - RTOG grade >=3 Chang et al (U of Florida) - NCI CTC grade >=2 Maximum likelihood fit - steroids and worse n = m = 0.38 TD50 = 28. Gy Maximum 40likelihood fit - 50 no steroids Mean Lung Dose (Gy) Maximum likelihood fit - steroids and worse Mean Lung Dose (Gy) 0.8 Observed RP Rate Mean Lung Dose (Gy)

11 Lung Observed RP Rate Graham et al. 999 (Washington U) - RTOG grade >=2 Seppenwoolde et al (Netherlands) - SWOG grade >=2 Moiseenko et al (Canada) - RTOG grade >=2 Willner et al (Germany) - NCI CTC grade >=2 Kim et al (Korea) - RTOG grade >=3 Yorke et al (MSKCC) - RTOG grade >=3 Chang et al (U of Florida) - NCI CTC grade >=2 Maximum likelihood fit - all RP n = m = 0.39 TD50 = 28.6 Gy Mean Lung Dose (Gy)

12 Parotid Gland Reference n m TD 50 (Gy) Endpoint Fractionation Scheme Parotid gland Burman et al Xerostomia.8-2 Gy q.d. Eisbruch et al RTOG grade 4 toxicity (stimulated.8-2 Gy q.d. salivary flow rate reduced to 25% pre- RT flow at 2 months) Schilstra and Meertens SSF 25% at 3 weeks 2 Gy q.d. 200 Roesink et al. 200 Braam et al SSF 25% at 6 weeks SSF 25% at 6 months SSF 25% at 2 months SSF 25% at 6 weeks SSF 25% at 6 months SSF 25% at 2 months SSF 25% at 5 years 2 Gy q.d. 2 Gy q.d.

13 Parotid Gland Observed Complication Rate n = m = 0.54 TD50 = 29.9 Gy Eisbruch et al. 999 (U of Michigan) Roesink et al. 200 (Netherlands) Scrimger et al (Canada) Maximum likelihood fit Mean Dose (Gy)

14 Esophagus Reference n m TD 50 (Gy) Endpoint Fractionation Scheme Esophagus Burman et al Clinical stricture/perforation.8-2 Gy q.d. Belderbos et al RTOG grade 2 AE Gy q.d.; normalized to 2 Gy/fr using α/β of 0 Gy Chapet et al RTOG grade 2 AE 2. Gy q.d.; normalized to 2 Gy/fr using α/β of 0 Gy This work RTOG grade 2 AE 2 Gy q.d.

15 Liver Reference n m TD 50 (Gy) Endpoint Fractionation Scheme Liver Burman et al Liver failure.8-2 Gy q.d. Lawrence et al. 992/ RTOG grade 3 RILD at 4 months Gy b.i.d. This work Ten Haken et al RTOG grade 3 RILD at 4 months Gy b.i.d.; normalized to.5 Gy/fr using α/β of 2 Gy Dawson et al RTOG grade 3 RILD at 4 months Gy b.i.d.; normalized to.5 Gy/fr using α/β of 2 Gy Dawson et al RTOG grade 3 RILD at 4 months Gy b.i.d.; normalized patients with liver metastases to.5 Gy/fr using α/β of 2 Gy primary hepatobiliary cancer patients Cheng et al NCI CTC grade 3 RILD at 4 months.8-2 Gy q.d. Cheng et al NCI CTC grade 3 RILD at 4 months.8-3 Gy q.d.; normalized to 2 Gy/fr using α/β of 2 Gy Xu et al NCI CTC grade 3 RILD at 4 months 4-6 Gy q.d Child-Pugh grade A liver cirrhosis Child-Pugh grade B liver cirrhosis

16 New LKB Model Parameters Organ n m TD 50 (Gy) Endpoint Fractionation Scheme Lung RTOG grade 2 RP 2 Gy q.d. (0.34, 0.45) (26.2, 3.4) Parotid gland SSF 25% at 3 months 2 Gy q.d. (0.42, 0.75) (26.4, 34.2) Esophagus RTOG grade 2 AE 2 Gy q.d. Liver RTOG grade 3 RILD at 4 months Gy b.i.d. Optic nerve Visual field defects and/or unilateral.8 Gy q.d. blindness Heart Pericarditis of any grade 2 Gy q.d. Brain stem Any new or aggravated cranial nerve deficit 0-20 Gy single fraction (radiosurgery) Rectum Severe proctitis/necrosis/stenosis/fistula.8-2 Gy q.d. Bladder RTOG grade 3 bladder complications 2 Gy q.d.

17 Conclusions Lyman model parameter estimates for nine critical organs identified These estimates are based on post- Emami experience and represent the next iteration in identifying reliable normal tissue complication data for biologically-based based treatment planning