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Objective. To allow the estimation of secondary cancer risks from radiation therapy treatment plans in a comprehensive and user-friendly Monte Carlo (MC) framework.Method. Patient planning computed tomography scans were extended superior-inferior using the International Commission on Radiological Protection's Publication 145 computational mesh phantoms and skeletal matching. Dose distributions were calculated with the TOPAS MC system using novel mesh capabilities and the digital imaging and communications in medicine radiotherapy extension interface. Finally, in-field and out-of-field cancer risk was calculated using both sarcoma and carcinoma risk models with two alternative parameter sets.Result. The TOPAS MC framework was extended to facilitate epidemiological studies on radiation-induced cancer risk. The framework is efficient and allows automated analysis of large datasets. Out-of-field organ dose was small compared to in-field dose, but the risk estimates indicate a non-negligible contribution to the total radiation induced cancer risk.Significance. This work equips the TOPAS MC system with anatomical extension, mesh geometry, and cancer risk model capabilities that make state-of-the-art out-of-field dose calculation and risk estimation accessible to a large pool of users. Furthermore, these capabilities will facilitate further refinement of risk models and sensitivity analysis of patient specific treatment options.

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BACKGROUND: Few studies have comprehensively investigated the long-term second cancer risk among adolescent and young adult (AYA, aged 15-39 years) cancer survivors. This study investigated the long-term second cancer risk by including the full range of first and second cancer combinations with at least 10 observations in the Netherlands between 1989 and 2018. MATERIALS AND METHODS: First and second primary cancer data of all 6-month AYA cancer survivors were obtained from the nationwide population-based Netherlands Cancer Registry. Excess cancer risk compared to the general population was assessed with standardized incidence ratio (SIR) and absolute excess risk (AER) statistics up to 25 years after diagnosis. Cumulative incidences were estimated, using death as a competing risk factor. Analyses were carried out with and without applying multiple cancer rules. RESULTS: The cohort included 99 502 AYA cancer survivors. Male survivors had a 2-fold higher risk of developing any cancer compared to the general population, whereas this was around 1.3-fold in females. AERs were 17.5 and 10.1 per 10 000 person-years for males and females. The long-term excess risk of cancer was significantly higher for most first and second primary cancer combinations, but comparable and lower risk estimates were also observed. Application of the multiple cancer rules resulted in a noticeable risk underestimation in melanoma, testicular, and breast cancer survivors. Risk outcomes remained similar in most cases otherwise. The cumulative incidence of second cancer overall increased over time up to 8.9% in males and 10.3% in females at 25 years' follow-up. Highest long-term cumulative incidences were observed among lymphoma survivors (13.3% males and 18.9% females). CONCLUSIONS: AYA cancer survivors have a higher cancer risk compared to the general population for most cancers up to 25 years after their initial cancer diagnosis. Additional studies that investigate risk factors for the specific cancer type combinations are needed to develop personalized follow-up strategies.

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Background: Radiation therapy, the most common form of cancer treatment, can result in late complications, such as secondary breast and thyroid cancers. Objective: This study aimed to evaluate the risk of secondary cancers using two radiobiological models of Excess Absolute Risk (EAR) and Excess Relative Risk (ERR) in patients with brain cancer undergoing radiotherapy for improved survival rates of cancer patients. Material and Methods: In this expository cross-sectional study, 45 patients under the age of 40 years underwent Whole Brain Radiotherapy (WBRT) using a compact accelerator in Shahid Ramezanzadeh Hospital, Yazd, Iran. Out-of-field organ dose measurement was performed using a Thermoluminescent Dosimeter (TLD) to determine the dose to thyroid and breast tissues. The risk of secondary cancers in these organs was calculated 3, 5, 10, 15, and 20 years after radiation therapy. Results: The mean values of thyroid cancer risk in men and women were 0.418±0.509 and 0.274±0.306, respectively. ERR values of breast cancer in 3-, 5-, 10-, 15-, and 20-year women undergoing radiation therapy were 1.084±2.938, 0.594±1.407, 0.248±0.497, 0.138±0.248, and 0.091±0.148, respectively. EAR values of breast cancer in 3-, 5-, 10-, 15-, and 20-year women following radiation therapy were 0.064±0.060, 0.077±0.071, 0.119±0.100, 0.178±0.248, and 0.259±0.178, respectively. Conclusion: After irradiation, the risk of secondary cancer is affected by factors, such as the patient's age and gender. The secondary thyroid cancer is higher than that of other organs, such as the breast, in the patients undergoing WBRT.

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Objective.CT-mesh hybrid phantoms (or 'hybrid(s)') made from integrated patient CT data and mesh-type reference computational phantoms (MRCPs) can be beneficial for patient-specific whole-body dose evaluation, but this benefit has yet to be evaluated for second cancer risk prediction. The purpose of this study is to compare the hybrid's ability to predict risk throughout the body with a patient-scaled MRCP against ground truth whole-body CTs (WBCTs).Approach.Head and neck active scanning proton treatment plans were created for and simulated on seven hybrids and the corresponding scaled MRCPs and WBCTs. Equivalent dose throughout the body was calculated and input into five second cancer risk models for both excess absolute and excess relative risk (EAR and ERR). The hybrid phantom was evaluated by comparing equivalent dose and risk predictions against the WBCT.Main results.The hybrid most frequently provides whole-body second cancer risk predictions which are closer to the ground truth when compared to a scaled MRCP alone. The performance of the hybrid relative to the scaled MRCP was consistent across ERR, EAR, and all risk models. For all in-field organs, where the hybrid shares the WBCT anatomy, the hybrid was better than or equal to the scaled MRCP for both equivalent dose and risk prediction. For out-of-field organs across all patients, the hybrid's equivalent dose prediction was superior than the scaled MRCP in 48% of all comparisons, equivalent for 34%, and inferior for 18%. For risk assessment in the same organs, the hybrid's prediction was superior than the scaled MRCP in 51.8% of all comparisons, equivalent in 28.6%, and inferior in 19.6%.Significance.Whole-body risk predictions from the CT-mesh hybrid have shown to be more accurate than those from a reference phantom alone. These hybrids could aid in risk-optimized treatment planning and individual risk assessment to minimize second cancer incidence.

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Proton therapy has the potential to provide survival and tumor control outcomes comparable and frequently superior to photon therapy. This has led to a significant concern in the medical physics community on the risk for the induction of second cancers in all patients and especially in younger patients, as they are considered more radiosensitive than adults and have an even longer expected lifetime after treatment. Thus, our purpose is to present an overview of the research carried out on the evaluation of out-of-field doses linked to second cancer induction and the prediction of this risk. Most investigations consisted of Monte Carlo simulations in passive beam facilities for clinical scenarios. These works established that equivalent doses in organs could be up to 200 mSv or 900 mSv for a brain or a craniospinal treatment, respectively. The major contribution to this dose comes from the secondary neutrons produced in the beam line elements. Few works focused on scanned-beam facilities, but available data show that, for these facilities, equivalent doses could be between 2 and 50 times lower. Patient age is a relevant factor in the dose level, especially for younger patients (by means of the size of the body) and, in addition, in the predicted risk by models (due to the age dependence of the radiosensitivity). For risks, the sex of the patient also plays an important role, as female patients show higher sensitivity to radiation. Thus, predicted risks of craniospinal irradiation can range from 8% for a 15-year-old male patient to 58% for a 2-year-old female patient, using a risk model from a radiological protection field. These values must be taken with caution due to uncertainties in risk models, and then dosimetric evaluation of stray radiation becomes mandatory in order to complement epidemiological studies and be able to model appropriate dose-response functions for this dose range. In this sense, analytical models represent a useful tool and some models have been implemented to be used for young patients. Research carried out so far confirmed that proton beam therapy reduces the out-of-field doses and second cancer risk. However, further investigations may be required in scanned-beam delivery systems.

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PURPOSE: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL. METHODS: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t­test with Bonferroni correction was used for comparison. RESULTS: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected. CONCLUSION: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM.

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PURPOSE: This study aimed at evaluating the clinical impact of full intensity-modulated radiotherapy (IMRT), hybrid IMRT (H-IMRT) and hybrid volumetric-modulated arc therapy (H-VMAT) for early-stage breast cancer with simultaneous integrated boost (SIB), in terms of plan quality and second cancer risk (SCR). METHODS: Three different plans were designed in full IMRT, hybrid IMRT, and hybrid VMAT for each of twenty patients with early-stage breast cancer. Target quality, organs at risk (OARs) sparing, and SCR were compared among the three plans for each case. RESULTS: In compared with H-IMRT, IMRT plans showed deterioration in terms of D2% of SIB, V10 of ipsilateral lung, and excess absolute risk (EAR) to contralateral lung (C-Lung) and esophagus. D2% and the homogeneity index (HI) of SIB, V5 of ipsilateral lung (I-Lung), the Dmean of the esophagus, the EAR to C-Lung and the esophagus with hybrid VMAT dramatically increased by 0.63%, 10%, 17.99%, 149.27%, 230.41%, and 135.29%, respectively (p = 0.024; 0.025; 0.046; 0.011; 0.000; 0.014). Dmean of the heart, the EAR to contralateral breast (C-Breast) and C-Lung by full IMRT was significantly decreased in comparison to the H-VMAT (4.67%, p = 0.033, 26.76%, p = 0.018; 48.05%, p = 0.036). CONCLUSION: The results confirmed that H-IMRT could achieve better target quality and OARs sparing than IMRT and H-VMAT for SIB radiotherapy of early-stage right breast cancer. H-IMRT was the best treatment option, while H-VMAT performed the worst among the three plans in terms of SCR to peripheral OARs.

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Out-of-field organs are not commonly designated as dose calculation targets during radiation therapy treatment planning, but they might entail risks of second cancer. Risk components include specific internal body scatter, which is a dominant source of out-of-field doses, and head leakage, which can be reduced by external shielding. Our simulation study quantifies out-of-field organ doses and estimates second cancer risks attributable to internal body scatter in whole-breast radiotherapy (WBRT) with or without additional regional nodal radiotherapy (RNRT), respectively, for right and left breast cancer using Monte Carlo code PHITS. Simulations were conducted using a complete whole-body female model. Second cancer risk was estimated using the calculated doses with a concept of excess absolute risk. Simulation results revealed marked differences between WBRT alone and WBRT plus RNRT in out-of-field organ doses. The ratios of mean doses between them were as large as 3.5-8.0 for the head and neck region and about 1.5-6.6 for the lower abdominal region. Potentially, most out-of-field organs had excess absolute risks of less than 1 per 10,000 persons-year. Our study surveyed the respective contributions of internal body scatter to out-of-field organ doses and second cancer risks in breast radiotherapy on this intact female model.

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PURPOSE: To estimate the risk for bladder and rectal cancer induction due to standard fractionated (SF) and moderately hypofractionated (HF) volumetric modulated arc therapy (VMAT) for prostate carcinoma. METHODS: Twelve patients with low or intermediate-risk of prostate cancer referred for external-beam radiotherapy were included in this study. Three computed tomography-based VMAT plans were created for each study participant. The first plan was generated by assuming patient's irradiation with SF-VMAT (78 Gy in 39 fractions). The second and third plans were created on the basis of two different HF schedules (HF-VMAT1 : 70 Gy in 30 fractions, HF:VMAT2 : 60 Gy in 20 fractions). Data from differential dose-volume histograms obtained by the above treatment plans were employed to calculate the organ equivalent dose (OED) of the bladder and rectum with the aid of a nonlinear model accounting for fractionation and proliferation effects. The calculated OED values were used to estimate the average lifetime attributable risk (LARav ) for the appearance of radiotherapy-induced secondary bladder and rectal malignancies. The lifetime risk of radiation carcinogenesis was compared with the respective organ-, and age-dependent lifetime intrinsic risk (LIR) of cancer development for unexposed males. RESULTS: The average OED of the rectum from SF-VMAT, HF-VMAT1 and HF-VMAT2 for prostate cancer was 972.0, 900.2, and 815.7 cGy, respectively. The corresponding values for bladder were 73.4, 72.3, and 71.0 cGy. The LARav for rectal cancer induction varied from 0.06% to 0.4% by the fractionation schedule used for irradiation and by the age of the patient at the time of treatment. The corresponding risk range related to the development of secondary bladder malignancies was 0.06-0.33%. The SF-VMAT, HF-VMAT1 and HF-VMAT2 led to an increase of the lifetime rectal cancer risk with respect to LIR by 2.2-9.8%, 2.0-9.1% and 1.8-8.2%, respectively, depending upon the patient's age. The corresponding elevation for bladder cancer induction was up to 8.0%, 7.9% and 7.7%. CONCLUSIONS: The use of VMAT for prostate carcinoma leads to a noteworthy increase of the lifetime risk for bladder and rectal cancer induction compared to that of unexposed people irrespective of the patient's age at the time of treatment and the applied fractionation scheme. The cancer risk data presented in this study may be taken into account by radiation oncologists and medical physicists in the selection of the optimal radiation therapy plan.

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PURPOSE: To estimate the second cancer risk associated with Hodgkin Lymphoma (HL) radiotherapy at supradiaphragmatic or infradiaphragmatic region, using the involved field (IFRT) and the involved site radiotherapy (ISRT). MATERIALS AND METHODS: IFRT and ISRT treatment plans were created for twenty HL patients. Three dimensional plans (3DRT) were employed for all patients. The organ equivalent dose (OED) and lifetime attributable risk (LAR) for organs at risk were estimated with mechanistic, plateau and bell-shaped model. Estimated risk values were compared with nominal risk of unexposed population. RESULTS: For supradiaphragmatic radiotherapy, the mean OED range was 0.63-8.53 Gy and 0.63-7.26 Gy for IFRT and ISRT, respectively. The corresponding range for infradiaphragmatic radiotherapy was 0.18-7.64 Gy and 0.80-4.95 Gy. The LAR for cancer induction in the partially in field organs at risk after IFRT was 0.5%-8.0% and 0.2%-9.3% at supradiaphragmatic and infradiaphragmatic regions, respectively. The corresponding risk after ISRT method was 0.5%-5.2% and 0.9%-6.0%. Estimated cancer risk for breast, lung, thyroid, colon and rectal with ISRT was found significantly reduced compared to IFRT. The risk of secondary malignancies for lung, mouth, pharynx, rectum and colon was assessed more than 1.2 times higher than nominal risk for IFRT. The respective risk using ISRT was above nominal only for pharyngeal cancer. CONCLUSION: ISRT compared with IFRT, results in decreased second cancer risk in most organs considered. Second cancer probability with IFRT was higher than the nominal risk for certain organs, while for ISRT remains higher only for pharyngeal cancer.

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Pediatric patients suffering from ependymoma are usually treated with cranial or craniospinal three-dimensional (3D) conformal radiotherapy (3DCRT). Intensity-modulated techniques spare dose to the surrounding tissue, but the risk for second malignancies may be increased due to the increase in low-dose volume. The aim of this study is to investigate if the flattening filter free (FFF) mode allows reducing the risk for second malignancies compared to the mode with flattening filter (FF) for intensity-modulated techniques and to 3DCRT. A reduction of the risk would be advantageous for treating pediatric ependymoma. 3DCRT was compared to intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) with and without flattening filter. Dose-volume histograms (DVHs) were compared to evaluate the plan quality and used to calculate the excess absolute risk (EAR) to develop second cancer in the brain. Dose verification was performed with a two-dimensional (2D) ionization chamber array and the out-of-field dose was measured with an ionization chamber to determine the EAR in peripheral organs. Delivery times were measured. Both VMAT and IMRT achieved similar plan quality in terms of dose sparing in the OAR and higher PTV coverage as compared to 3DCRT. Peripheral dose in low-dose region, which is proportional to the EAR in organs located in this region, for example, gonads, bladder, or bowel, could be significantly reduced using FFF. The lowest peripheral EAR and lowest delivery times were hereby achieved with VMATFFF . The EAR calculated based on DVH in the brain could not be reduced using FFF mode. VMATFFF improved the target coverage and homogeneity and kept the dose in the OAR similar compared to 3DCRT. In addition, delivery times were significantly reduced using VMATFFF . Therefore, for radiotherapy of ependymoma patients, VMATFFF may be considered advantageous for the combination of Elekta Synergy linac and Oncentra External Beam planning system used in this study.

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BACKGROUND: Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider's full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. RESULTS: We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. CONCLUSION: VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.

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BACKGROUND: The purpose of this study was to estimate the secondary cancer risk of thyroid in standard radiotherapy methods which are commonly used for breast cancer patients. METHODS: A total of 64 breast cancer patients (their age range was around 50 years old) who referred to Seyed-Al-Shohada hospital (Isfahan, Iran) were included in this study. The radiotherapy of the mentioned patients was performed using 6-MV photon beams. Dose measurements were also done using thermoluminescent dosimeters. Calculation of the risk of developing secondary cancer in thyroid was done using the Biological Effects of Ionizing Radiation Committee VII and recommended quantity of the International Radiation Protection Commission, excess relative risk. RESULTS: The mean radiation dose to thyroid for the tangential beams, tangential field with supraclavicular (SC) field, and also a tangential field with SC field in modified radical mastectomy (MRM) were 0.883 ± 0.472, 1.512 ± 0.365, and 1.587 ± 0.37, respectively. The risk of developing secondary thyroid cancer over a period of 5 years after breast cancer therapy in the tangential, tangential with a SC field, and also tangential beam with SC field in MRM were 9.974 ± 4.318, 17.891 ± 0.365, and 18.783 ± 4.384, respectively. The mean of the measured thyroid doses in patients treated with tangent fields was significantly lower than the patients under the irradiation of the tangent fields with SC field (P < 0.001). CONCLUSIONS: Using radiation protection equipment is suggested for breast cancer patients who treated with the studied radiotherapy methods.

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Objective To investigate the dosimetric characteristics between helical tomotherapy ( HT) and intensity-modulated radiotherapy ( IMRT) plans in children receiving craniospinal irradiation and estimate the risk of radiogenic second cancer according to the excess absolute risk ( EAR) model. Methods Computer-tomography scans of 15 children who received craniospinal irradiation between 2012 and 2017 were selected. HT and IMRT plans were designed for each patient after contouring the volumes of tumors and organ at risks ( OARs) and then the homogeneous index ( HI) , conformity index ( CI) , the maximum dose and the mean dose of OAR,V10 and V20 were analyzed to optimize the clinical treatment plan. The second cancer risk was estimated by DVH of each organ and EAR model and statistically compared between HT and IMRT. Results Both two plans met the clinical requirements in target coverage ( 100％ dose≥95％ target volume).The HI in the HT group was significantly superior to that in the IMRT group (P=0. 000) whereas no significant difference was noted in CI between two groups. Compared with the IMRT plan, HT plan possessed absolute advantage in protecting hippocampus and the D2％ and Dmean were significantly lower ( P=0. 000).As for the protection of OAR, the Dmax, Dmean and V20 of thyroid (P=0. 001,0. 002 and 0. 014) and Dmax,V10 of heart ( P=0. 001 and 0. 003) in the HT plan were significantly lower than those in the IMRT plan. In terms of second cancer risk, HT plan yielded a significantly higher second cancer risk for thyroid and lung compared with IMRT the EAR in thyroid was 28. 666 vs. 26. 926 ( P=0. 010 ) and 20. 496 vs. 18.922( P=0. 003) in lung. Both plans yielded a relatively high second cancer risk for stomach ( P=0. 248), whereas a low second cancer risk for liver (P=0. 020). Conclusions HT plan is superior to IMRT plan in the hippocampus-sparing craniospinal irradiation in children. However, HT plan yields a high second cancer risk for thyroid and lung. Consequently, the balance between the carcinogenic risk and the effect on other normal tissues should be assessed in the establishment of therapeutic plan.

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In absolute terms: second cancer risks from radiotherapy of first cancers in adults are small compared to the benefits from radiotherapy but this is not so for radiotherapy of childhood cancers. Moreover, the radiation dose dependence of cancer induction differs between organs and tissues. The organ-specific dose dependence of second cancer risks may indicate the existence of different radiobiological mechanisms. As an inevitable consequence of the age dependence of organ sensitivity to second cancer induction, the organ/tissue weighting factors which have been proposed by ICRP for calculating effective dose (the dose unit Sv) and for risk estimation in the general population should not be used in medical radiation exposures. In adult cancer radiotherapy, the most common unwanted effect is local tumour recurrence whereas both, severe late normal tissue damage and radiation-induced second cancers are rare, around 1% of locally controlled cancer patients. In childhood cancers, local failures are rare (<10% in some cancers) yet second cancers are more common than uncontrolled primaries. The main reason for considering particle radiotherapy for childhood cancers is the possibility to exploit their physical characteristics to reduce the radiation exposure to organs and tissues close to and distant from the primary cancer which is to be targeted. However, the relative biological effectiveness of the radiation doses within the proton beam is not a constant and the relative biological effectiveness of the neutrons is not known as far as the mechanisms of late normal tissue damage and second cancer risk are concerned. In view of the highly charged discussions of the potential risks of treatment-induced seecond cancers from the neutron contamination of exposure doses in out-of-PTV critical organs a comprehensive European project called ANDANTE was performed which integrated the disciplines of radiation physics, molecular biology, systems biology modelling and epidemiology in order to investigate the RBE of induction of cancer from exposure to neutrons compared to photons. Since out-of-field "effective" neutron doses from proton therapy are smaller than the photon stray doses whichever reasonable RBE is chosen for comparison, and since the absolute risk of radiation-induced second cancer rates are in the order of 1% in the cohorts of adult patients who have been treated in the past with methods which caused relatively high out-of-field doses to large body volumes, it is highly unlikely that such patients treated in future with highly conformal particle therapy are at a higher radiation-induced second cancer risk than those patients treated with photons and described before. Still, the potential risks of second cancers from scattered proton radiotherapy for childhood cancers may cause concern. Yet, the overall risk of undesired consequences of radiation exposure of children which are more complex and manifold than in adult patients (including developmental, neurocognitive, hormonal and growth impairment effects) are likely to be very much reduced by the better focussing of the radiation dose in the target offered by particle radioherapy. This benefit may far outweigh the still hypothetical second cancer risk from particle radiotherapy in pediatric radiotherapy.

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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.

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OBJECTIVES: The aim of this study is to estimate second cancer risk (SCR) in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using a mechanistic radiobiological model. The model also takes into account patient age at exposure and the gender-specific correction factors of SCR. MATERIALS AND METHODS: Fifty IMRT and VMAT plans were selected for the study. Monte Carlo-based dose calculation engine was used for dose calculation. Appropriate model parameters were taken from the literature for the mechanistic model to calculate excess absolute risk (EAR), lifetime attributable risk, integral dose and relative risk (RR) for lungs, contralateral breast, heart, and spinal cord. RESULTS: The mean monitor unit (MU) in IMRT and VMAT plans were 751.1 ± 133.3 and 1004.8 ± 180, respectively, for IMRT and VMAT. The mean EAR values with age correction were 44.6 ± 11.9, 11.2 ± 6.4, 5.4 ± 4.0, 1.4 ± 0.5, and 0.3 ± 0.2 for left lung, right lung, contralateral breast, heart, and spinal cord, respectively, for the IMRT treatments and 54.6 ± 20.6, 30.2 ± 12.0, 13.8 ± 8.6, 1.6 ± 0.6, and 0.9 ± 0.5 for the VMAT treatments in units of 10,000 PY. The RR of 6.7% and 9.1%, respectively, for IMRT and VMAT found in our study using computational models is in close comparison with the value reported in a large epidemiological breast cancer study. CONCLUSIONS: VMAT plans had a higher risk of developing second malignancy in lung, contralateral breast, heart, and cord compared to IMRT plans. However, the increase in risk was found to be marginal compared to IMRT. Incorporating the age correction factor decreased the risk of contralateral breast SCR. No strong correlation was found between EAR and MU.

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BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome characterized by a very high lifetime cancer risk and an early age at diagnosis of a wide cancer spectrum. Precise estimates for the risk of first and subsequent cancers are lacking. METHODS: The National Cancer Institute's Li-Fraumeni Syndrome Study includes families meeting the diagnostic criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or ≥3 cancers. Herein, we estimated the cumulative risk and annual hazards for first and second cancers among TP53 mutation carriers (TP53 positive [TP53+]) using MATLAB statistical software. RESULTS: This study evaluated 286 TP53+ individuals from 107 families. The cumulative cancer incidence was 50% by age 31 years among TP53+ females and 46 years among males, and nearly 100% by age 70 years for both sexes. Cancer risk was highest after age 20 years for females, mostly due to breast cancer, whereas among males the risk was higher in childhood and later adulthood. Among females, the cumulative incidence rates by age 70 years for breast cancer, soft tissue sarcoma, brain cancer, and osteosarcoma were 54%, 15%, 6%, and 5%, respectively. Among males, the incidence rates were 22%, 19%, and 11%, respectively, for soft tissue sarcoma, brain cancer, and osteosarcoma. Approximately 49% of those with 1 cancer developed at least another cancer after a median of 10 years. The average age-specific risk of developing a second cancer was comparable to that of developing a first cancer. CONCLUSIONS: The cumulative cancer risk in TP53 + individuals was very high and varied by sex, age, and cancer type. Additional work, including prospective risk estimates, is needed to better inform personalized risk management. Cancer 2016;122:3673-81. © 2016 American Cancer Society.

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