Risk of a second cancer after radiotherapy

Transcription

1 Risk of a second cancer after radiotherapy Francesco d Errico University of Pisa, Italy Yale University, USA

2 Medical radiological procedures worldwide 2.5 billion diagnostic radiological examinations 78% medical X-rays, 21% dental X-rays and about 1% administration of radionuclides 5.5 million complete courses of radiation therapy 85 % teletherapy treatments, of which 21% concern the female breast, lung (17%), head and brain (13%), gynecological tumors (11%), prostate (7%), lymphoma (5%) and rectum (4%); treatments of leukemia and benign diseases each account for ~3%. 7.5 % brachytherapy 7.5% radiopharmaceutical therapy Source: UN Scientific Committee on the Effects of Atomic Radiation (2000).

3 Age distribution of patients undergoing radiotherapy in HCL I countries

4 Intensity-modulated radiation therapy (IMRT) Dynamic MLC Tomotherapy A l B l

5 IMRT rationale By means of inverse planning, IMRT produces plans that give dramatically precise isodose curves and theoretically remarkable sparing of sensitive tissue.

6 IMRT rationale Survival rates expected to increase where gains in local control are the key factor Toxicity is reduced, e.g. in head and neck IMRT salivary gland dose is reduced dramatically w/o reduction in tumor control

7 IMRT debated clinical issues Narrow margins vs imprecision & penumbra Tumor edge definition Verification of treatment plan Variability on patient immobilization Proposed dose escalation (-> 100 Gy) Unknown long term effects of high doses on Neighboring normal tissues Normal structures within a primary tumor target (e.g. nerves or vessels)

8 IMRT debated radiation safety issues Protection of the patient Low-dose, normal tissue exposure Larger low-dose volume (10% target dose) Longer treatments, higher leakage term Protection of personnel Workloads for shielding design

9 Cancer induction by radiotherapy Second tumors after radiotherapy observed in a population of 31,000 radiotherapy patients treated between 1969 and Over 200 re-admitted for radiotherapy because of a newly developed malignant tumour. Analysis was performed of spatial relation between new tumour and primary treatment fields, and of dose at the site of origin. Doerr et al. J Radiat Prot

10 Cancer induction by radiotherapy 58% new tumours developed in volume receiving < 6 Gy (> 20% developed in volume receiving 0-1 Gy) 35% developed in volume receiving Gy Doerr et al. J Radiat Prot 2003

11 Cancer induction by radiotherapy 50% of new tumours developed in the margin region (-2.5 to + 5 cm from field edge ICRU definition). 10% within the field (up to -2.5 from field edge) ~10% in the adjacent region (5-20 cm from edge)

12 Cancer induction by radiotherapy The increased incidence in the margin region suggests that radiation may at least contribute to tumorigenesis, which may or may not be accompanied by genetic susceptibility or other factors of the patient. In Doerr s study, the latent time to clinical manifestation of second primary tumours was 18 years for low-energy x-rays. We are approaching this time since the introduction of IMRT.

13 Risk models for cancer induction by radiotherapy It has long been recognized that the linear dose risk model should be modified at high doses to account for cell kill, repopulation and other effects. A simple model involves the modulation of the linear dose response by an exponential cell kill term. Studies of patients with induced cancers following radiotherapy have indicated dose risk relationships at variance with this model and suggest that plateau dose-risk responses may be valid for some induced cancers

14 Organ Equivalent Dose (OED) concept Various non-uniform dose distributions in an organ are equivalent and correspond to the same OED if they cause the same radiation-induced risk of cancer. Thus for a particular organ and a linear dose response, the OED is given by: Where: V i is the volume of voxel i within the organ V is the total volume of the organ D i is the dose to voxel i.

15 Organ Equivalent Dose (OED) concept For the case of a linear dose response relationship, OED rad-ther linear is simply the mean organ dose. (The subscript rad-ther has been suggested by Schneider and Kaser-Hotz (2005) to avoid confusion with the quantity Equivalent Dose). Other dose models can be similarly described, i.e. for a linearexponential dose response: and for a plateau response: Where: α org and δ org are parameters associated with the organ response.

16 Organ Equivalent Dose (OED) concept The risk of radiation-induced cancer in the organ (I org ) is then given by: Where I 0 org is the low dose risk of radiation-induced cancer per unit dose and OEDrad-thermodel is the Organ Equivalent Dose for one of the used response models. I 0 org is given in several reviews of low dose cancer induction risk (e.g. UNSCEAR 2000).

17 Whole body dose for head and neck tomotherapy (Peacock-Clinac 6/100) 120 x 40 x 18.5 cm 3 water-equivalent plastic block (trunk) attached to 16.5 x 16.5 x 18 cm 3 polystyrene block (head). 3 x 3 x 1 mm 3 LiF TLD chips Mutic et al. IJROBP 1998

18 Whole body dose for head and neck tomotherapy (Peacock-Clinac 6/100) Treatment plan of five sequential 290 arc-based deliveries, each using an average of 360 MUs 200 cgy delivered per fraction to a 7.9 cm long, 8 cm diameter, cylindrical target volume embedded in the polystyrene box. Measurements repeated with shut leaves to determine leakage Mutic et al. IJROBP 1998

19 Whole body dose for head and neck tomotherapy (Peacock-Clinac 6/100) Distance (cm) The internally scattered dose is significant near the target, but becomes negligible relative to the leakage dose beyond 15 cm from the target. Mutic et al. IJROBP

20 Whole body dose for head and neck tomotherapy (Peacock-Clinac 6/100) Distance (cm) Dose at 10 cm from the target volume, due to internal scatter and leakage, is approximately 2.5% of the total target dose, decreasing to ~ 0.5% at 30 cm. Mutic et al. IJROBP 1998

21 Whole body dose for head and neck tomotherapy (Peacock-Clinac 6/100) Distance (cm) Beyond ~ 30 cm, the measured dose becomes relatively uniform throughout the phantom. Mutic et al. IJROBP 1998

22 Mutic et al. IJROBP 1998 Conclusions The whole-body dose equivalent from a tomotherapy treatment is greater than that from conventional radiation therapy. Based on Mutic et al, for a 70 Gy IMRT course, the dose at 50 cm from the target is ~ 0.2 Gy Further studies are required to assess the trade-off between improved dose distribution conformality and a possible slight increase in radiation-induced fatal malignancies. 22

23 IMRT radiation risks to a fetus Based on Mutic et al, for a 70 Gy IMRT course, the x-ray dose at 50 cm from the target is ~ 0.2 Gy AAPM TG 36 Med Phys 1995