Assessment of radiation-induced second cancer risks in proton therapy and IMRT for organs inside the primary radiation field.

There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can significantly reduce the risk for developing an in-field second malignancy. The risk depends on treatment planning parameters, i.e. an analysis based on our formalism could be applied within treatment planning programs to guide treatment plans for pediatric patients.

Adjuvant radiation therapy for early stage seminoma: proton versus photon planning comparison and modeling of second cancer risk.

PURPOSE: Given concerns of excess malignancies following adjuvant radiation for seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to assess dose distributions to organs at risk and model rates of second cancers. MATERIALS AND METHODS: Ten stage I seminoma patients who were treated with conventional para-aortic AP-PA photon radiation to 25.5 Gy at Massachusetts General Hospital had PBT plans generated (AP-PA, PA alone). Dose differences to critical organs were examined. Risks of second primary malignancies were calculated. RESULTS: PBT plans were superior to photons in limiting dose to organs at risk. PBT decreased dose by 46% (8.2 Gy) and 64% (10.2 Gy) to the stomach and large bowel, respectively (p<0.01). Notably, PBT was found to avert 300 excess second cancers among 10,000 men treated at a median age of 39 and surviving to 75 (p<0.01). CONCLUSIONS: In this study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of early-stage seminoma. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted.

Comparison of second cancer risk due to out-of-field doses from 6-MV IMRT and proton therapy based on 6 pediatric patient treatment plans.

BACKGROUND AND PURPOSE: This study compared 6-MV IMRT and proton therapy in terms of organ specific second cancer lifetime attributable risks (LARs) caused by scattered and secondary out-of-field radiation. MATERIALS AND METHODS: Based on simulated organ doses, excess relative and excess absolute risk models were applied to assess organ-specific LARs. Two treatment sites (cranium and central spine) were considered involving six treatment volumes and six patient ages (9-month, 4-year, 8-year, 11-year, 14-year, and adult). RESULTS: The LARs for thyroid cancer from a 6 cm diameter field treating a brain lesion in a 4-year old patient were estimated to be 1.1% and 0.3% in passive proton therapy and IMRT, respectively. However, estimated LARs for bladder cancer, more than 25 cm from the field edge for the same patient and treatment field, were estimated to be 0.2% and 0.02% from IMRT and proton therapy, respectively. Risks for proton beam scanning was found to be an order of magnitude smaller compared to passive proton therapy. CONCLUSION: In terms of out-of-field risks, IMRT offers advantage close to the primary field and an increasing advantage for passive proton therapy is noticed with increasing distance to the field. Scanning proton beam therapy shows the lowest risks.

Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients.

The purpose of this study was to assess lateral out-of-field doses in 6 MV IMRT (intensity modulated radiation therapy) and compare them with secondary neutron equivalent dose contributions in proton therapy. We simulated out-of-field photon doses to various organs as a function of distance, patient's age, gender and treatment volumes based on 3, 6, 9 cm field diameters in the head and neck and spine region. The out-of-field photon doses to organs near the field edge were found to be in the range of 2, 5 and 10 mSv Gy(-1) for 3 cm, 6 cm and 9 cm diameter IMRT fields, respectively, within 5 cm of the field edge. Statistical uncertainties calculated in organ doses vary from 0.2% to 40% depending on the organ location and the organ volume. Next, a comparison was made with previously calculated neutron equivalent doses from proton therapy using identical field arrangements. For example, out-of-field doses for IMRT to lung and uterus (organs close to the 3 cm diameter spinal field) were computed to be 0.63 and 0.62 mSv Gy(-1), respectively. These numbers are found to be a factor of 2 smaller than the corresponding out-of-field doses for proton therapy, which were estimated to be 1.6 and 1.7 mSv Gy(-1) (RBE), respectively. However, as the distance to the field edge increases beyond approximately 25 cm the neutron equivalent dose from proton therapy was found to be a factor of 2-3 smaller than the out-of-field photon dose from IMRT. We have also analyzed the neutron equivalent doses from an ideal scanned proton therapy (assuming not significant amount of absorbers in the treatment head). Out-of-field doses were found to be an order of magnitude smaller compared to out-of-field doses in IMRT or passive scattered proton therapy. In conclusion, there seem to be three geometrical areas when comparing the out-of-target dose from IMRT and (passive scattered) proton treatments. Close to the target (in-field, not analyzed here) protons offer a distinct advantage due to the lower integral dose. Out-of-field, but within approximately 25 cm from the field edge, the scattered photon dose in IMRT turned out to be roughly a factor of 2 lower than the neutron equivalent dose from proton therapy for the fields considered in this study. At larger distances to the field (beyond approximately 25 cm), protons offer an advantage, resulting in doses that are roughly a factor of 2-3 lower.

Neutron equivalent doses and associated lifetime cancer incidence risks for head & neck and spinal proton therapy.

In this work we have simulated the absorbed equivalent doses to various organs distant to the field edge assuming proton therapy treatments of brain or spine lesions. We have used computational whole-body (gender-specific and age-dependent) voxel phantoms and considered six treatment fields with varying treatment volumes and depths. The maximum neutron equivalent dose to organs near the field edge was found to be approximately 8 mSv Gy(-1). We were able to clearly demonstrate that organ-specific neutron equivalent doses are age (stature) dependent. For example, assuming an 8-year-old patient, the dose to brain from the spinal fields ranged from 0.04 to 0.10 mSv Gy(-1), whereas the dose to the brain assuming a 9-month-old patient ranged from 0.5 to 1.0 mSv Gy(-1). Further, as the field aperture opening increases, the secondary neutron equivalent dose caused by the treatment head decreases, while the secondary neutron equivalent dose caused by the patient itself increases. To interpret the dosimetric data, we analyzed second cancer incidence risks for various organs as a function of patient age and field size based on two risk models. The results show that, for example, in an 8-year-old female patient treated with a spinal proton therapy field, breasts, lungs and rectum have the highest radiation-induced lifetime cancer incidence risks. These are estimated to be 0.71%, 1.05% and 0.60%, respectively. For an 11-year-old male patient treated with a spinal field, bronchi and rectum show the highest risks of 0.32% and 0.43%, respectively. Risks for male and female patients increase as their age at treatment time decreases.