Automatic Radiobiological Comparison of Radiation Therapy Plans: An Application to Gastric Cancer.

(1) Aim: This study was conducted to radiobiologically compare radiotherapy plans for gastric cancer with a newly developed software tool. (2) Methods: Treatment planning was performed on two computational phantoms simulating adult male and female patients. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for gastric cancer were generated with three-photon beam energies. The equivalent uniform dose (EUD), tumor control probability (TCP) of the target and normal tissue control probability (NTCP) of eight different critical organs were calculated. A new software was employed for these calculations using the EUD-based model and dose-volume-histogram data. (3) Results: The IMRT and VMAT plan led to TCPs of 51.3-51.5%, whereas 3D-CRT gave values up to 50.2%. The intensity-modulated techniques resulted in NTCPs of (5.3 × 10-6-3.3 × 10-1)%. The corresponding NTCPs from 3D-CRT were (3.4 × 10-7-7.4 × 10-1)%. The above biological indices were automatically calculated in less than 40 s with the software. (4) Conclusions: The direct and quick radiobiological evaluation of radiotherapy plans is feasible using the new software tool. The IMRT and VMAT reduced the probability of the appearance of late effects in most of the surrounding critical organs and slightly increased the TCP compared to 3D-CRT.

Assessment of Radiation-Induced Bladder and Bowel Cancer Risks after Conventionally and Hypo-Fractionated Radiotherapy for the Preoperative Management of Rectal Carcinoma.

Preoperative management of rectal carcinoma can be performed by employing either conventionally or hypo-fractionated Radiotherapy (CFRT or HFRT, respectively), delivered by Intensity Modulated Radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT) plans, employing 6 MV or 10 MV photon beams. This study aims to dosimetrically and radiobiologically compare all available approaches, with emphasis on the risk of radiation-induced second cancer to the bladder and bowel. Computed Tomography (CT) scans and relevant radiotherapy contours from 16 patients were anonymized and analyzed retrospectively. For each case, CFRT of 25 × 2 Gy and HFRT of 5 × 5 Gy were both considered. IMRT and VMAT plans using 6 MV and 10 MV photons were prepared. Plan optimization was performed, considering all clinically used plan quality indices and dose-volume constraints for the critical organs. Resulting dose distributions were analyzed and compared. Moreover, the Lifetime Attributable Risk (LAR) for developing radiation-induced bladder and bowel malignancies were assessed using a non-linear mechanistic model, assuming patient ages at treatment of 45, 50, 55 and 60 years. All 128 plans created were clinically acceptable. Risk of second bladder cancer reached 0.26% for HFRT (5 × 5 Gy) and 0.19% for CFRT (25 × 2 Gy) at the age of 45. Systematically higher risks were calculated for HFRT (5 × 5 Gy) as compared to CFRT (25 × 2 Gy), with 6 MV photons resulting in slightly increased LAR, as well. Similar or equal bowel cancer risks were calculated for all techniques and patient ages investigated (range 0.05-0.14%). This work contributes towards radiotherapy treatment protocol selection criteria for the preoperative irradiation of rectal carcinoma. However, more studies are needed to establish the associated radiation-induced risk of each RT protocol.

Risk of developing radiogenic cancer following photon-beam radiotherapy for Graves' orbitopathy.

PURPOSE: The objective of this study was to estimate the probability for cancer development due to radiotherapy for Graves' orbitopathy with 6 MV x rays. METHODS: Orbital irradiation was simulated with the MCNP code. The radiation dose received by 10 out-of-field organs having a strong disposition for carcinogenesis was calculated with Monte Carlo methods. These dose calculations were used to estimate the organ-dependent lifetime attributable risk (LAR) for cancer induction in 30- and 50-yr-old males and females on the basis of the linear model suggested by the BEIR-VII report. Differential dose-volume histograms derived from patients' three-dimensional (3D) radiotherapy plans were employed to determine the organ equivalent dose (OED) of the brain which was partly exposed to primary radiation. The OED and the relevant LAR for brain cancer development were assessed with the plateau, bell-shaped and mechanistic models. The radiotherapy-induced cancer risks were compared with the lifetime intrinsic risk (LIR) values for unexposed population. RESULTS: The radiation dose range to organs excluded from the treatment volume was 0.1-91.0 mGy for a target dose of 20 Gy. These peripheral organ doses increased the LIRs for cancer development of unexposed 30- and 50-yr-old males up to 1.0% and 0.2%, respectively. The corresponding elevations after radiotherapy of females were 2.0% and 0.4%. The use of nonlinear models gave an OED range of the brain of 482.0-562.5 mGy depending upon the model used for analysis and the patient's gender. The elevation of the LIR for developing brain malignancies after radiotherapy of 30-yr-old males and females reached to 13.3% and 16.6%, respectively. The corresponding increases after orbital irradiation at the age of 50 yr were 6.7% and 8.3%. CONCLUSIONS: The level of the LIR increase attributable to radiation therapy for GO varied widely by the organ under examination and the age and gender of the exposed subject. This study provides the required data to quantify the elevation of these baseline cancer risks following orbital irradiation.

Second cancer risk assessments after involved-site radiotherapy for mediastinal Hodgkin lymphoma.

PURPOSE: This study was conducted to provide second cancer risk assessments attributable to involved-site radiotherapy (ISRT) of mediastinal Hodgkin lymphoma (HL) and to compare these risks with those from the conventional involved-field radiation therapy (IFRT). METHODS: Both ISRT and IFRT plans were made for 11 patients (six females, five males) with HL in the region of mediastinum. All three-dimensional plans involved 6 MV photon beams and delivered 30 Gy to the target site. Differential dose-volume histograms were defined for the lung, female breast, and esophagus which were partly included within the planned treatment fields. The patient-specific organ equivalent dose (OED) and the relevant lifetime attributable risk (LAR) of developing malignancies in each of the above critical organs were determined with the aid of a mechanistic, plateau and bell-shaped models. The LAR estimates were compared with the baseline risks for unexposed people. RESULTS: The OED range of lung, breast, and esophagus calculated by the ISRT plans was 176.1-360.2, 19.5-124.1, and 42.6-157.7 cGy, respectively. The resultant LARs of developing lung and breast cancer as estimated by the three different models were at least 1.8 and 5.3 times lower than the baseline risks, respectively. The probability for the appearance of radiation-induced esophageal malignancies from ISRT in males was also up to 3.8 times smaller than the nominal incidence cancer rates. The corresponding probability in irradiated females exceeded the baseline risks. The estimated lifetime risks for lung and breast cancer induction due to ISRT were systematically and significantly lower than those from the IFRT irrespective of the model used for analysis (P < 0.05). No significant difference was found between the LARs for esophageal cancer development estimated by the ISRT and IFRT plans (P = 0.63). CONCLUSIONS: The presented second cancer risk data may be of value in the selection of the optimal radiotherapy technique for the management of mediastinal HL and in the subsequent follow-up of irradiated patients.

Organ-specific radiation-induced cancer risk estimates due to radiotherapy for benign pigmented villonodular synovitis.

Pigmented villonodular synovitis (PVNS) is a benign disease affecting synovial membranes of young and middle-aged adults. The aggressive treatment of this disorder often involves external-beam irradiation. This study was motivated by the lack of data relating to the radiation exposure of healthy tissues and radiotherapy-induced cancer risk. Monte Carlo methodology was employed to simulate a patient's irradiation for PVNS in the knee and hip joints with a 6 MV photon beam. The average radiation dose received by twenty-two out-of-field critical organs of the human body was calculated. These calculations were combined with the appropriate organ-, age- and gender-specific risk coefficients of the BEIR-VII model to estimate the lifetime probability of cancer development. The risk for carcinogenesis to colon, which was partly included in the treatment fields used for hip irradiation, was determined with a non-linear mechanistic model and differential dose-volume histograms obtained by CT-based 3D radiotherapy planning. Risk assessments were compared with the nominal lifetime intrinsic risk (LIR) values. Knee irradiation to 36 Gy resulted in out-of-field organ doses of 0.2-24.6 mGy. The corresponding range from hip radiotherapy was 1.2-455.1 mGy whereas the organ equivalent dose for the colon was up to 654.9 mGy. The organ-specific cancer risks from knee irradiation for PVNS were found to be inconsequential since they were at least 161.5 times lower than the LIRs irrespective of the patient's age and gender. The bladder and colon cancer risk from radiotherapy in the hip joint was up to 3.2 and 6.6 times smaller than the LIR, respectively. These cancer risks may slightly elevate the nominal incidence rates and they should not be ignored during the patient's treatment planning and follow-up. The probabilities for developing any other solid tumor were more than 20 times lower than the LIRs and, therefore, they may be considered as small.

Radiation dose and cancer risk to out-of-field and partially in-field organs from radiotherapy for symptomatic vertebral hemangiomas.

PURPOSE: Vertebral hemangiomas (VHs) are the most common benign tumors of the spine that may cause bone resorption. Megavoltage irradiation is usually the treatment of choice for the management of symptomatic VHs. The current study was conducted to estimate the risk for carcinogenesis from radiotherapy of this benign disease on the basis of the calculated radiation doses to healthy organs. METHODS: The Monte Carlo N-particle transport code was employed to simulate the irradiation with 6 MV x-rays of a VH presented in the cervical, upper thoracic, lower thoracic, and lumbar spine. The average radiation dose (Dav) received by each critical organ located outside the primarily irradiated area was calculated. Three-dimensional treatment plans were also generated for the VHs occurring at the four different sites of the spinal cord based on patients' computed tomography data. The organ equivalent dose (OED) to each radiosensitive structure, which was partly encompassed by the applied treatment fields, was calculated with the aid of differential dose-volume histograms. The Dav and the OED values were combined with a linear-no-threshold model and a nonlinear mechanistic model, respectively, to estimate the organ-, age-, and gender-specific lifetime attributable risks (LARs) for cancer development. The estimated risks were compared with the respective nominal lifetime intrinsic risks (LIRs) for the unexposed population. RESULTS: For a standard target dose of 34 Gy, the OED varied from 0.39-5.15 Gy by the organ of interest and the irradiation site. The Dav range for the out-of-field organs was 4.9 × 10(-4) to 0.56 Gy. The LAR for the appearance of malignancies in the partially in-field organs after radiotherapy of male and female patients was (0.08%-1.8%) and (0.09%-1.9%), respectively. These risk values were 1.5-15.5 times lower when compared to the respective LIRs. The lifetime probability for out-of-field cancer induction in irradiated males and females was (2.5 × 10(-4) to 7.7 × 10(-2))% and (1.4 × 10(-4) to 2.6 × 10(-1))%, respectively. The above risks were one to four orders of magnitude lower than the LIRs. CONCLUSIONS: The probability for the development of out-of-field malignancies due to radiotherapy for VHs is trivial with respect to the nominal risk for unexposed population. The respective cancer risks to partially in-field organs are smaller than the nominal probabilities but they should not be considered as inconsiderable. These risks may be taken into account during the follow-up of patients treated for a symptomatic VH.

Radiotherapy for stage I seminoma of the testis: Organ equivalent dose to partially in-field structures and second cancer risk estimates on the basis of a mechanistic, bell-shaped, and plateau model.

PURPOSE: The aim of the current study was to (a) calculate the organ equivalent dose (OED) and (b) estimate the associated second cancer risk to partially in-field critical structures from adjuvant radiotherapy for stage I seminoma of the testis on the basis of three different nonlinear risk models. METHODS: Three-dimensional plans were created for twelve patients who underwent a treatment planning computed tomography of the abdomen. The plans for irradiation of seminoma consisted of para-aortic anteroposterior and posteroanterior fields giving 20 Gy to the target site with 6 MV photons. The OED of stomach, colon, liver, pancreas, and kidneys, that were partially included in the treatment volume, was calculated using differential dose-volume histograms. The mechanistic, bell-shaped, and plateau models were employed for these calculations provided that organ-specific parameters were available for the subsequent assessment of the excess absolute risk (EAR) for second cancer development. The estimated organ-specific lifetime risks were compared with the respective nominal intrinsic probabilities for cancer induction. RESULTS: The mean OED, which was calculated from the patients' treatment plans, varied from 0.54 to 6.61 Gy by the partially in-field organ of interest and the model used for dosimetric calculations. The difference between the OED of liver derived from the mechanistic model with those from the bell-shaped and plateau models was less than 1.8%. An even smaller deviation of 1.0% was observed for colon. For the rest organs of interest, the differences between the OED values obtained by the examined models varied from 8.6% to 50.0%. The EAR for stomach, colon, liver, pancreas, and kidney cancer induction at an age of 70 yr because of treatment of a typical 39-yr-old individual was up to 4.24, 11.39, 0.91, 3.04, and 0.14 per 10 000 persons-yr, respectively. Patient's irradiation was found to elevate the lifetime intrinsic risks by 8.3%-63.0% depending upon the organ of interest and the model employed for risk analysis. CONCLUSIONS: Radiotherapy for stage I seminoma of the testis may result in an excess risk for the appearance of secondary malignancies in partially in-field organs. The organ- and model-dependent second cancer risk assessments of this study may be of value for patient counseling and follow-up.

Radiation therapy for stage IIA and IIB testicular seminoma: peripheral dose calculations and risk assessments.

This study was conducted to calculate the peripheral dose to critical structures and assess the radiation risks from modern radiotherapy for stage IIA/IIB testicular seminoma. A Monte Carlo code was used for treatment simulation on a computational phantom representing an average adult. The initial treatment phase involved anteroposterior and posteroanaterior modified dog-leg fields exposing para-aortic and ipsilateral iliac lymph nodes followed by a cone-down phase for nodal mass irradiation. Peripheral doses were calculated using different modified dog-leg field dimensions and an extended conventional dog-leg portal. The risk models of the BEIR-VII report and ICRP-103 were combined with dosimetric calculations to estimate the probability of developing stochastic effects. Radiotherapy for stage IIA seminoma with a target dose of 30 Gy resulted in a range of 23.0-603.7 mGy to non-targeted peripheral tissues and organs. The corresponding range for treatment of stage IIB disease to a cumulative dose of 36 Gy was 24.2-633.9 mGy. A dose variation of less than 13% was found by altering the field dimensions. Radiotherapy with the conventional instead of the modern modified dog-leg field increased the peripheral dose up to 8.2 times. The calculated heart doses of 589.0-632.9 mGy may increase the risk for developing cardiovascular diseases whereas the testicular dose of more than 231.9 mGy may lead to a temporary infertility. The probability of birth abnormalities in the offspring of cancer survivors was below 0.13% which is much lower than the spontaneous mutation rate. Abdominoplevic irradiation may increase the lifetime intrinsic risk for the induction of secondary malignancies by 0.6-3.9% depending upon the site of interest, patient's age and tumor dose. Radiotherapy for stage IIA/IIB seminoma with restricted fields and low doses is associated with an increased morbidity. These data may allow the definition of a risk-adapted follow-up scheme for long-term testicular cancer survivors.

Photon-beam radiotherapy in pregnant patients: can the fetal dose be limited to 10 cGy or less?

PURPOSE: To estimate fetal dose and its components from three-dimensional conformal radiotherapy for several malignancies presented during pregnancy. MATERIALS AND METHODS: Fetal dose was measured from radiotherapy for Hodgkin's lymphoma and for tumors in the region of nasopharynx, breast and lung. Anthropomorphic phantoms were used to simulate an average pregnant patient at the first, second and third trimesters of gestation. Thermoluminescent dosemeters (TLD) were employed for fetal dose measurements. Phantom exposures were also performed to estimate fetal dose due to head leakage, scatter from collimators and beam modifiers and scatter generated inside the phantom (Din). All treatments were delivered for 6 MV photon beams. RESULTS: Radiotherapy of Hodgkin's lymphoma resulted in a fetal dose of 5.6-57.9 cGy depending upon the gestational age and the distance between the fetal level and the field edge. The corresponding dose ranges for treatment of nasopharyngeal, breast and lung cancer was 4.0-17.1 cGy, 3.9-24.8 cGy and 5.7-74.3 cGy, respectively. The Din at the first trimester of gestation was always smaller than 10 cGy for all examined malignancies. Pregnancy progression resulted in Din values above or below 10 cGy depending upon the treatment site and gestational age. CONCLUSION: This study provides data about the fetal exposure and the contribution of Din to the total fetal dose from conformal radiation therapy. The Din knowledge prior to patient's irradiation enables radiation oncologists and medical physicists to decide whether fetal dose may be limited to 10 cGy or less with or without the introduction of special shielding materials.

Out-of-field organ doses and associated radiogenic risks from para-aortic radiotherapy for testicular seminoma.

PURPOSE: The aims of this study were to (a) calculate the radiation dose to out-of-field organs from radiotherapy for stage I testicular seminoma and (b) estimate the associated radiogenic risks. METHODS: Monte Carlo methodology was employed to model radiation therapy with typical anteroposterior and posteroanterior para-aortic fields on an anthropomorphic phantom simulating an average adult. The radiation dose received by all main and remaining organs that defined by the ICRP publication 103 and excluded from the treatment volume was calculated. The effect of field dimensions on each organ dose was determined. Additional therapy simulations were generated by introducing shielding blocks to protect the kidneys from primary radiation. The gonadal dose was employed to assess the risk of heritable effects for irradiated male patients of reproductive potential. The lifetime attributable risks (LAR) of radiotherapy-induced cancer were estimated using gender- and organ-specific risk coefficients for patient ages of 20, 30, 40, and 50 years old. The risk values were compared with the respective nominal risks. RESULTS: Para-aortic irradiation to 20 Gy resulted in out-of-field organ doses of 5.0-538.6 mGy. Blocked field treatment led to a dose change up to 28%. The mean organ dose variation by increasing or decreasing the applied field dimensions was 18.7% ± 3.9% and 20.8% ± 4.5%, respectively. The out-of-field photon doses increased the lifetime intrinsic risk of developing thyroid, lung, bladder, prostate, and esophageal cancer by (0.1-1.4)%, (0.4-1.1)%, (2.5-5.4)%, (0.2-0.4)%, and (6.4-9.2)%, respectively, depending upon the patient age at exposure and the field size employed. A low risk for heritable effects of less than 0.029% was found compared with the natural incidence of these defects. CONCLUSIONS: Testicular cancer survivors are subjected to an increased risk for the induction of bladder and esophageal cancer following para-aortic radiotherapy. The probability for the appearance of any other malignant disease to out-of-field organs was slightly elevated in respect to the nominal cancer incidence rates.

Cancer risk estimates from radiation therapy for heterotopic ossification prophylaxis after total hip arthroplasty.

PURPOSE: Heterotopic ossification (HO) is a frequent complication following total hip arthroplasty. This study was conducted to calculate the radiation dose to organs-at-risk and estimate the probability of cancer induction from radiotherapy for HO prophylaxis. METHODS: Hip irradiation for HO with a 6 MV photon beam was simulated with the aid of a Monte Carlo model. A realistic humanoid phantom representing an average adult patient was implemented in Monte Carlo environment for dosimetric calculations. The average out-of-field radiation dose to stomach, liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was calculated. The organ-equivalent-dose to colon, that was partly included within the treatment field, was also determined. Organ dose calculations were carried out using three different field sizes. The dependence of organ doses upon the block insertion into primary beam for shielding colon and prosthesis was investigated. The lifetime attributable risk for cancer development was estimated using organ, age, and gender-specific risk coefficients. RESULTS: For a typical target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field dimensions and organ location relative to the field edge. Blocked field irradiations resulted in a dose range of 1.4-146.3 mGy. The most probable detriment from open field treatment of male patients was colon cancer with a high risk of 564.3 × 10(-5) to 837.4 × 10(-5) depending upon the organ dose magnitude and the patient's age. The corresponding colon cancer risk for female patients was (372.2-541.0) × 10(-5). The probability of bladder cancer development was more than 113.7 × 10(-5) and 110.3 × 10(-5) for males and females, respectively. The cancer risk range to other individual organs was reduced to (0.003-68.5) × 10(-5). CONCLUSIONS: The risk for cancer induction from radiation therapy for HO prophylaxis after total hip arthroplasty varies considerably by the treatment parameters, organ site in respect to treatment volume and patient's gender and age. The presented risk estimates may be useful in the follow-up studies of irradiated patients.