Risk Of Second Cancer Research Articles

Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer

IntroductionBreast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk. Patients and MethodsThirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups. ResultsEstrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer. ConclusionThe decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.

Racial and ethnic differences in risk of second primary cancers among prostate cancer survivors.

Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.

Suppression of innate immune signaling molecule, MAVS, reduces radiation-induced bystander effect

Purpose Mitochondrial antiviral signaling (MAVS) protein, located in the mitochondrial out-membrane, is necessary for IFN-beta induction and IFN-stimulated gene expression in response to external stress such as viral invasion and ionizing radiation (IR). Although the involvement of radiation induced bystander effect (RIBE) has been investigated for decades for secondary cancer risk related to radiotherapy, the underlying regulatory mechanisms remain largely unclear, especially the roles played by the immune factors such as MAVS. Material and methods MAVS gene knockout cells using CRISPR/Cas9 technology were used as donor cells or recipient cells to assess the role of MAVS in RIBE by means of co-cultured system. The micronucleus and γH2AX foci in the recipient cells were counted to demonstrate the degree of RIBE. The reactive oxygen species (ROS) level in the recipient was measured using the fluorescent dye 2′7′-dichlorofluorescein. Results Firstly, we found that MAVS expression level was different in A549, BEAS-2B, U937 and HepG2 cells. Cell co-culture experiments showed that MAVS participate in RIBE. Interestingly, the RIBE response was more significant in recipient cells with higher level of MAVS (i.e. A549) than that in recipient cells showing lower level of MAVS (i.e. BEAS-2B). Further, the bystander response was dramatically suppressed in MAVS-silenced A549 and BEAS-2B recipient cells. MAVS-silenced recipient cells exhibited lower level of ROS induced by IR. Conclusions Our results indicated that the innate immune signaling molecule MAVS in recipient cells participate in RIBE. ROS is an important factor in RIBE via MAVS pathway and MAVS may be a potential target for the precise radiotherapy and radioprotection.

Reducing the Risk of Secondary Lung Cancer in Treatment Planning of Accelerated Partial Breast Irradiation.

Purpose: Adjuvant accelerated partial breast irradiation (APBI) results in low local recurrence risks. However, the survival benefit of adjuvant radiotherapy APBI for low-risk breast cancer might partially be offset by the risk of radiation-induced lung cancer. Reducing the lung dose mitigates this risk, but this could result in higher doses to the ipsilateral breast. Different external beam APBI techniques are equally conformal and homogenous, but the intermediate to low dose distribution differs. Thus, the risk of toxicity is different. The purpose of this study is to quantify the trade-off between secondary lung cancer risk and breast dose in treatment planning and to compare an optimal coplanar and non-coplanar technique.Methods: A total of 440 APBI treatment plans were generated using automated treatment planning for a coplanar VMAT beam-setup and a non-coplanar robotic stereotactic radiotherapy beam-setup. This enabled an unbiased comparison of two times 11 Pareto-optimal plans for 20 patients, gradually shifting priority from maximum lung sparing to maximum ipsilateral breast sparing. The excess absolute risks of developing lung cancer and breast fibrosis were calculated using the Schneider model for lung cancer and the Avanzo model for breast fibrosis.Results: Prioritizing lung sparing reduced the mean lung dose from 2.2 Gy to as low as 0.3 Gy for the non-coplanar technique and from 1.9 Gy to 0.4 Gy for the coplanar technique, corresponding to a 7- and 4-fold median reduction of secondary lung cancer risk, respectively, compared to prioritizing breast sparing. The increase in breast dose resulted in a negligible 0.4% increase in fibrosis risk. The use of non-coplanar beams resulted in lower secondary cancer and fibrosis risks (p < 0.001). Lung sparing also reduced the mean heart dose for both techniques.Conclusions: The risk of secondary lung cancer of external beam APBI can be dramatically reduced by prioritizing lung sparing during treatment planning. The associated increase in breast dose did not lead to a relevant increase in fibrosis risk. The use of non-coplanar beams systematically resulted in the lowest risks of secondary lung cancer and fibrosis. Prioritizing lung sparing during treatment planning could increase the overall survival of early-stage breast cancer patients by reducing mortality due to secondary lung cancer and cardiovascular toxicity.

Study of out-of-field dose in photon radiotherapy: A commercial treatment planning system versus measurements and Monte Carlo simulations.

PurposeAn accurate assessment of out‐of‐field dose is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. Although treatment planning systems (TPSs) calculate dose distributions outside the treatment field, little is known about the accuracy of these calculations. The aim of this work is to thoroughly compare the out‐of‐field dose distributions given by two algorithms implemented in the Monaco TPS, with measurements and full Monte Carlo simulations.MethodsOut‐of‐field dose distributions predicted by the collapsed cone convolution (CCC) and Monte Carlo (MCMonaco) algorithms, built into the commercially available Monaco version 5.11 TPS, are compared with measurements carried out on an Elekta Axesse linear accelerator. For the measurements, ion chambers, thermoluminescent dosimeters, and EBT3 film are used. The BEAMnrc code, built on the EGSnrc system, is used to create a model of the Elekta Axesse with the Agility collimation system, and the space phase file generated is scored by DOSXYZnrc to generate the dose distributions (MCEGSnrc). Three different irradiation scenarios are considered: (a) a 10 × 10 cm2 field, (b) an IMRT prostate plan, and (c) a three‐field lung plan. Monaco's calculations, experimental measurements, and Monte Carlo simulations are carried out in water and/or in an ICRP110 phantom.ResultsFor the 10 × 10 cm2 field case, CCC underestimated the dose, compared to ion chamber measurements, by 13% (differences relative to the algorithm) on average between the 5% and the ≈2% isodoses. MCMonaco underestimated the dose only from approximately the 2% isodose for this case. Qualitatively similar results were observed for the studied IMRT case when compared to film dosimetry. For the three‐field lung plan, dose underestimations of up to ≈90% for MCMonaco and ≈60% for CCC, relative to MCEGSnrc simulations, were observed in mean dose to organs located beyond the 2% isodose.ConclusionsThis work shows that Monaco underestimates out‐of‐field doses in almost all the cases considered. Thus, it does not describe dose distribution beyond the border of the field accurately. This is in agreement with previously published works reporting similar results for other TPSs. Analytical models for out‐of‐field dose assessment, MC simulations or experimental measurements may be an adequate alternative for this purpose.

Estimation of secondary cancer risk after radiotherapy in high-risk prostate cancer patients with pelvic irradiation.

We aimed to estimate the risk of secondary cancer after radiotherapy (RT) in high‐risk prostate cancer (HRPC) patients with pelvic irradiation. Computed tomography data of five biopsy‐proven HRPC patients were selected for this study. Two different planning target volumes (PTV1 and PTV2) were contoured for each patient. The PTV1 included the prostate, seminal vesicles, and pelvic lymphatics, while the PTV2 included only the prostate and seminal vesicles. The prescribed dose was 54 Gy for the PTV1 with a sequential boost (24 Gy for the PTV2). Intensity‐modulated RT (IMRT) and volumetric modulated arc therapy (VMAT) techniques were used to generate treatment plans with 6 and 10 MV photon energies with the flattening filter (FF) or flattening filter‐free (FFF) irradiation mode. The excess absolute risks (EARs) were calculated and compared for the bladder, rectum, pelvic bone, and soft tissue based on the linear‐exponential, plateau, full mechanistic, and specific mechanistic sarcoma dose‐response model. According to the models, all treatment plans resulted in similar risks of secondary bladder or rectal cancer and pelvic bone or soft tissue sarcoma except for the estimated risk of the bladder according to the full mechanistic model using IMRT(6MV;FF) technique compared with VMAT techniques with FFF options. The overall estimation of EAR indicated that the radiation‐induced cancer risk due to RT in HRPC was lower for bladder than the rectum. EAR values ranged from 1.47 to 5.82 for bladder and 6.36 to 7.94 for rectum, depending on the dose–response models used. The absolute risks of the secondary pelvic bone and soft tissue sarcoma were small for the plans examined. We theoretically predicted the radiation‐induced secondary cancer risk in HRPC patients with pelvic irradiation. Nevertheless, prospective clinical trials, with larger patient cohorts with a long‐term follow‐up, are needed to validate these model predictions.

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

Background The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Material and methods Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. Results IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2–3.4 Gy (median: 1.9 Gy) in FB and 0.0–1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2–2.4% in FB and 0.0–1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0–1.5% and 0–2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0–2.2%). Conclusion According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.

Out-Of-Field Dose Measurement and Second Cancer-Risk Estimation Following External Beam Radiotherapy and Brachytherapy for Cervical Cancer Treatment: A Phantom Study

Introduction: The present study aimed to measure the scatter and leakage dose received by out-of-field organs while delivering Radiotherapy (RT) treatment of cervical cancer. Moreover, this study estimated the risk of second cancer (SC). The doses to out-of-field organs were measured using a lithium fluoride (TLD 100) dosimeter while delivering External Beam Radiotherapy (EBRT) by 6 MV photon beam with Brachytherapy Boost (BB) treatment in the humanoid phantom. Material and Methods: The excess absolute risk of SC for the stomach, colon, liver, lung, breast, and kidney, as well as excess relative risk for the thyroid, were estimated based on Biological Effects of Ionizing Radiation VII report. Results: The out-of-field organ doses varied with respect to distance between organs. The colon (3DCRT-282.13 cGy and IMRT-381.24 cGy in 25 fractions) and kidney (70.65 cGy in 3 fractions) received the highest doses with EBRT and BB, respectively. For most of the aforementioned organs, the calculated dose was 0.2 Gy/fraction according to the treatment planning system. With the age at exposure (i.e., 30 years) as a reference, the highest LARs were associated with the colon (0.74%) and breast (2.76%) in 3DCRT plus BB and IMRT plus BB, respectively. The lifetime attributable risk of SC was also shown to decrease with increasing the age at exposure for all the organs. Conclusion: Although all the evaluated out-of-field organs in this study showed some levels of risk, the risk was more frequently reported for the colon, stomach, and breast with IMRT technique than that in 3DCRT.

Assessment of Radiation-Induced Secondary Cancer Risks In Breast Cancer Patients Treated with 3D Conformal Radiotherapy

Introduction: In the current study, radiation-induced secondary cancers risks (SCRs) have been evaluated in irradiated organs following three-dimensional conformal radiation therapy (3D-CRT) of breast cancer using the BEIR (Biological Effects of Ionizing Radiation) VII models. Material and Methods: Sixty patients with left-sided breast cancer were chosen for this study and who were treated with a total breast dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were retrieved and values of mean organs dose were computed. SCRs to the heart, ipsilateral lung, liver, thyroid, and contralateral were estimated using both excess relative risk (ERR) and excess absolute risks (EAR) models as proposed by BEIR VII committee of the U.S National Academy of Sciences.Average values of organ dose to these 60 patients were 6.8, 15.9, 3.7, 4.5 and 1.5 Gy in the thyroid, ipsilateral lung, contralateral breast, heart, and liver, respectively. Results: From the BEIR VII models, ERR incidence was estimated to be 21.2, 5.0, 1.6 and 1.4 Gy-1 for the ipsilateral lung, thyroid, heart, and liver, respectively. EAR for cancer incidence was calculated as 105, 45.8, 15.8 and 4.35 Gy-1 for these same organs. Conclusion: The study showed SCRs quantitatively to various organs for patients with breast cancer who received 3D-CRT. We found that 3D-CRT treatment is associated with a relatively high SCR in the lung.

Cancer risk after breast proton therapy considering physiological and radiobiological uncertainties

BackgroundThe reduced normal tissue dose burden from protons can reduce the risk of second cancer for breast cancer patients. Breathing motion and the impact of variable relative biological effectiveness (RBE) are however concerns for proton dose distributions. This study aimed to quantify the impact of these factors on risk predictions from proton and photon therapy. Materials and methodsTwelve patients were planned in free breathing with protons and photons to deliver 50 Gy (RBE) in 25 fractions (assuming RBE = 1.1 for protons) to the left breast. Second cancer risk was evaluated with several models for the lungs, contralateral breast, heart and esophagus as organs at risk (OARs). Plans were recalculated on CT-datasets acquired in extreme phases to account for breathing motion. Proton plans were also recalculated assuming variable RBE for a range of radiobiological parameters. ResultsThe OARs received substantially lower doses from protons compared to photons. The highest risks were for the lungs (average second cancer risks of 0.31% and 0.12% from photon and proton plans, respectively). The reduced risk with protons was maintained, even when breathing and/or RBE variation were taken into account. Furthermore, while the total risks from the photon plans were seen to increase with the integral dose, no such correlation was observed for the proton plans. ConclusionsProtons have an advantage over the photons with respect to the induction of cancer. Uncertainties in physiological movements and radiobiological parameters affected the absolute risk estimates, but not the general trend of lower risk associated with proton therapy.

Abstract A018: Using qualitative methods to develop health messages aimed to reduce secondhand smoke exposure among African American breast cancer survivors in a rural state

Abstract Purpose. This study aimed to develop health messages that help African American breast cancer survivors reduce exposure to secondhand smoke in the home. African American women are disproportionately impacted by tobacco exposures and cancer mortality. Cigarette smoking decreases functional status (e.g., fatigue, pain) and increases complications related to breast reconstruction and the risk for secondary cancers. Understanding knowledge, attitudes, and beliefs related to tobacco and sociocultural and environmental influences may inform the development of messages that protect breast cancer survivors from the harm of smoke. Methods. We used a sequential design to conduct semi-structured interviews, photovoice interviews, and focus groups that informed message development related to secondhand smoke exposure. African American women breast cancer survivors aged 30-65 years, who smoked cigarettes or cigars in past 30 days or lived with a smoker, and were low income were invited to participate. Interviews assessed knowledge related to breast reconstruction and the prevention of secondary cancers; perceived susceptibility and severity related to the harms of tobacco; subjective norms; attitudes toward using tobacco and implementing smokefree home rules; perceived benefits and complexity of implementing smokefree home rules; and intentions to adopt smokefree home rules. Participants who completed the interviews (n=12) were invited to use photovoice to capture the socio-environmental context of survivorship and women’s motivations for making changes in tobacco exposure (n=9). Data from the interviews and photovoice were used to develop 16 messages related to secondhand smoke exposure. An iterative process was used to obtain feedback on each message (e.g., The smoke from cigarettes, pipes, and cigars of any kind is the same. Keep your home safe from secondhand smoke) from focus group participants (n=12). Results. Forty percent of African American women breast cancer survivors who completed the interviews reported current smoking and 54% had expired CO levels &amp;gt; 7 ppm. Most women felt that cigarettes cause some harm, but also stated that no one knows how each person is affected. Some women felt that occasional smoking was not harmful, that secondhand smoke was as bad as smoking, and that it is a gamble as to whether anything would happen if exposed to tobacco smoke. Some women expressed that smoking did not affect their breast reconstruction surgery while others felt that it slowed the healing process, or were unclear about its effects on surgery. Women who provided feedback on the messages during focus groups stated that people say secondhand smoke causes cancer, but they were unclear of its effects. Women felt that health messages needed to convey the type of cancers caused by secondhand smoke. Conclusions. Our study provided helpful information that informed the development of messages that can be used to increase awareness of the harms of secondhand smoke. Citation Format: Nakita Lovelady, Pebbles Fagan, Camille Hart, Michael Preston, Tiffany Haynes, Ronda Henry-Tillman. Using qualitative methods to develop health messages aimed to reduce secondhand smoke exposure among African American breast cancer survivors in a rural state [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A018.

Abstract IA38: What causes the increased risk of acute lymphoblastic leukemia in Latinos?

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and, despite high cure rates, remains one of the leading causes of cancer-related mortality in children. Moreover, childhood ALL survivors are faced with severe long-term treatment-related morbidities, including increased risk of cardiovascular disease, secondary cancers, and pulmonary disease. Children of Latino ethnicity have the highest incidence of ALL in the United States. This increased risk likely has a genetic component, although the rising incidence of ALL in recent decades, which is increasing fastest in Latinos, points towards a role for environmental exposures. In this talk, I will discuss recent research from our group and others that has shed light on the potential etiologies of the increased ALL risk in Latinos. Genome-wide association studies (GWAS) of childhood ALL have pinpointed several risk loci at genes involved in B-cell development and hematopoiesis. In our earlier studies of ALL in the genetically admixed Latino population of California, we capitalized on their altered linkage disequilibrium patterns (compared to non-Latino whites) to identify putative causal variants, including a missense SNP in CDKN2A. More recently, we performed a large multiethnic GWAS of ALL including Latinos, non-Latino whites, and African-Americans, and identified new ALL risk loci at 8q24 and IKZF3. Fine-mapping at known loci also helped to confirm an independent risk locus at chromosome 10p12.31 and pinpointed a likely causal variant in an enhancer region for BMI1. Our group and others previously showed that the risk allele frequencies of several loci, including ARID5B, PIP4K2A, and GATA3, are higher in Latino populations and are associated with Native American ancestry. In two recent, independent GWAS of ALL in Latinos, a novel risk locus was identified at the erythroblast transformation-specific (ETS)-related gene (ERG) on chromosome 21, which was found to confer stronger leukemia risk in Latinos than in non-Latino whites. Moreover, within Latinos the effect of this risk locus increased with increasing Native American ancestry. We subsequently confirmed ERG as the first identified genetic risk locus for ALL in children with Down syndrome (DS-ALL), in which the effect size was again stronger in Latino than in non-Latino white children with DS. Our research group has also identified varied associations between Latinos and non-Latino whites for risk factors pertaining to immune stimulation (childhood contacts) and infection (cytomegalovirus). Future studies of ALL risk factors in Latinos, including even larger GWAS, polygenic risk score analysis, admixture mapping, as well as continued investigation of environmental risk factors, will be critical for our understanding the etiology of this disease and for identifying possible avenues to reduce the ethnic disparity in ALL incidence. Citation Format: Adam J. de Smith, Qianxi Feng, Kyle M. Walsh, Soyoung Jeon, Libby M. Morimoto, Andrew T. DeWan, Charleston Chiang, Catherine Metayer, Xiaomei Ma, Joseph L. Wiemels. What causes the increased risk of acute lymphoblastic leukemia in Latinos? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA38.

Measurement of Neutron Contamination at Different Points in the Radiotherapy Room

Radyoterapi, kanser tedavisinde kullanılan en önemli tedavi yöntemlerinden birisidir. Ancak, radyoterapide yüksek enerjili foton ve elektron demetlerinin kullanımı sırasında (&amp;gt;7 MV) lineer hızlandırıcı kafasında bulunan ağır metallerden kaynaklı nötron kirliliği oluşmaktadır. Bu durum, hedef hacimde ve çevresindeki diğer organlarda nötron kirliliğinden kaynaklı doz belirsizliğine neden olmakta ve ikincil kanser riski oluşturmaktadır. Bu çalışmada, 18 MV foton enerjisinde, Elekta Synergy lineer hızlandırıcıda Thermo Scientific Rad Eye NL marka nötron dedektörü ile alan açıklığının ve eşmerkeze olan uzaklığın nötron doz hızına olan etkisi incelenmiştir. Ayrıca, alan açıklığının nötron doz hızı üzerindeki etkisi eşmerkezde, eşmerkezden farklı uzaklıklarda, radyoterapi odası kapısının içi ve dışında, konsol odasında ölçümler alınarak araştırılmıştır. Radyoterapide, 18 MV enerjili fotonların neden olduğu nötron kirliliğinden kaynaklı doz belirsizliğinin ikincil kanser riskini artırabileceği öngörülmüştür. Bu nedenle, radyoterapide istenmeyen fotonötron dozunun dikkate alınmasının çok önemli olduğu sonucuna varılmıştır.

Outcomes of lung cancer screening among cancer survivors: An NCCN institution experience.

1595 Background: In 2013, the USPTF recommended low-dose CT (LDCT) screening for individuals at high risk of lung cancer based on data from the National Lung Screening Trial. However, the trial excluded participants with cancer diagnosis &lt; 5 years except for non-melanoma skin cancer, making it unclear whether the data will be generalizable to cancer survivors. This population, while at increased risk of secondary lung cancer, may be prone to false positive results due to anatomic defects or recurrent cancers. Our NCCN institution serves a large number of cancer survivors. We evaluated the outcomes of LDCT screening and the adherence to annual screening among cancer survivors, compared with individuals without cancer history (IWC). Methods: Prospectively maintained database of LDCT screening participants was analyzed. Eligibility was per NCCN criteria and cancer survivors needing regular chest CT were not offered LDCT. Participants were asked to complete a self-administered questionnaire on risk factors. Positive result was defined as Lung-RADS ≥3, corresponding to nodule ≥6 mm. Adherence to LDCT screening was defined as having T1 screening, excluding those &lt; 18 months from T0 at time of analysis. Predicted risk of lung cancer was calculated per PLCOm2012 model. Results: To date, 454 subjects have undergone LDCT screening. Positive results occurred in 60 subjects (13.2%) at T0; lung cancer was diagnosed in 10 subjects (2.2%); and other cancers were diagnosed in 5 subjects (1.1%). There were 152 cancer survivors, including survivors of breast (52), prostate (26), bladder or kidney (19), lung (14), and head and neck cancer (13). The median time from cancer treatment to LDCT screening was 6 years (range 0-55). Cancer survivors were older than IWC: median age 67.4 vs. 63.5 years ( p&lt; 0.001) and more likely to be active smokers: 37.5% vs. 29.5%, ( p= 0.09). The median predicted risk of lung cancer at 6 year was 5.5% vs. 3.2%, ( p= 0.15). No significant difference in the screening outcomes was found between groups. Among cancer survivors (N = 152), positive screening occurred in 15 (9.9%); lung cancer was diagnosed in 1 (0.7%); and other cancers were diagnosed in 3 subjects (1.9%). Non-adherence to LDCT screening occurred in 31 out of 152 cancer survivors (20.4%), compared with 81 out of 262 (30.9%) IWC, ( p= 0.02). Conclusions: About one-third of LDCT screenings at this NCCN institution occurred among cancer survivors. We found no evidence of increased false positive results. However, a higher rate of adherence to annual screening was observed among cancer survivors than IWC.

Second cancer risk after primary cancer treatment with three-dimensional conformal, intensity-modulated, or proton beam radiation therapy.

The comparative risks of a second cancer diagnosis are uncertain after primary cancer treatment with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), or proton beam radiotherapy (PBRT). Pediatric and adult patients with a first cancer diagnosis between 2004 and 2015 who received 3DCRT, IMRT, or PBRT were identified in the National Cancer Database from 9 tumor types: head and neck, gastrointestinal, gynecologic, lymphoma, lung, prostate, breast, bone/soft tissue, and brain/central nervous system. The diagnosis of second cancer was modeled using multivariable logistic regression adjusting for age, follow-up duration, radiotherapy (RT) dose, chemotherapy, sociodemographic variables, and other factors. Propensity score matching also was used to balance baseline characteristics. In total, 450,373 patients were identified (33.5% received 3DCRT, 65.2% received IMRT, and 1.3% received PBRT) with median follow-up of 5.1years after RT completion and a cumulative follow-up period of 2.54million person-years. Overall, the incidence of second cancer diagnosis was 1.55 per 100 patient-years. In a comparison between IMRT versus 3DCRT, there was no overall difference in the risk of second cancer (adjusted odds ratio [OR], 1.00; 95% CI, 0.97-1.02; P=.75). By comparison, PBRT had an overall lower risk of second cancer versus IMRT (adjusted OR, 0.31; 95% CI, 0.26-0.36; P<.0001). Results within each tumor type generally were consistent in the pooled analyses and also were maintained in propensity score-matched analyses. The risk of a second cancer diagnosis was similar after IMRT versus 3DCRT, whereas PBRT was associated with a lower risk of second cancer risk. Future work is warranted to determine the cost-effectiveness of PBRT and to identify the population best suited for this treatment.

Radiation-Induced Secondary Cancer Risk Assessment in Patients With Lung Cancer After Stereotactic Body Radiotherapy Using the CyberKnife M6 System With Lung-Optimized Treatment.

BackgroundTo evaluate the lifetime secondary cancer risk (SCR) of stereotactic body radiotherapy (SBRT) using the CyberKnife (CK) M6 system with a lung-optimized treatment (LOT) module for lung cancer patients.MethodsWe retrospectively enrolled 11 lung cancer patients curatively treated with SBRT using the CK M6 robotic radiosurgery system. The planning treatment volume (PTV) and common organs at risk (OARs) for SCR analysis included the spinal cord, total lung, and healthy normal lung tissue (total lung volume - PTV). Schneider’s full model was used to calculate SCR according to the concept of organ equivalent dose (OED).ResultsCK-LOT-SBRT delivers precisely targeted radiation doses to lung cancers and achieves good PTV coverage and conformal dose distribution, thus posing limited SCR to surrounding tissues. The three OARs had similar risk equivalent dose (RED) values among four different models. However, for the PTV, differences in RED values were observed among the models. The cumulative excess absolute risk (EAR) value for the normal lung, spinal cord, and PTV was 70.47 (per 10,000 person-years). Schneider’s Lnt model seemed to overestimate the EAR/lifetime attributable risk (LAR).ConclusionFor lung cancer patients treated with CK-LOT optimized with the Monte Carlo algorithm, the SCR might be lower. Younger patients had a greater SCR, although the dose–response relationship seemed be non-linear for the investigated organs, especially with respect to the PTV. Despite the etiological association, the SCR after CK-LOT-SBRT for carcinoma and sarcoma, is low, but not equal to zero. Further research is required to understand and to show the lung SBRT SCR comparisons and differences across different modalities with motion management strategies.

First person profile: Leslie L. Robison, PhD: A world-renowned epidemiologist, Dr. Robison played key roles in developing both the national Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort Study.

First person profile: Leslie L. Robison, PhD: A world-renowned epidemiologist, Dr. Robison played key roles in developing both the national Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort Study.

Estimation of radiation-induced, organ-specific, secondary solid-tumor occurrence rates with total body irradiation and total marrow irradiation treatments

PurposeWe aimed to predict and compare radiation-induced, organ-specific, secondary solid-tumor occurrence risks from conventional total body irradiation (TBI) and total marrow irradiation (TMI) for patients undergoing hematopoietic cell transplant. Methods and MaterialsWe retrospectively selected 20 patients who received TMI treatments before hematopoietic cell transplant. Ten patients (5 men; 5 women) received 12 Gy to the skeletal bones, lymph nodes, and spleen, and the other 10 patients (5 men; 5 women) received an escalated dose of 20 Gy to the same targets and 12 Gy to the brain and liver. A conventional TBI treatment plan was generated for each patient with a prescription dose of 12 Gy, using anterior-posterior and posterior-anterior photon beams with lung shielding and a chest wall boost with electron beams. Secondary cancer risks were estimated using linear-exponential and plateau models for major organs. ResultsAt the 12 Gy dose level, using the linear-exponential model, the total radiation-induced secondary solid-tumor risks for major organs were 159.3 ± 8.7 for men and 221.5 ± 14.4 for women per 10,000 people per year with the TMI plans, which is a reduction of 38.8% and 32.9%, respectively, compared with those with the TBI plans. At the 20 Gy dose level, the risks were 220.3 ± 8.3 for men and 298.5 ± 9.3 for women with the TMI plans, which is a reduction of 14.6% and 9.2%, respectively, compared with those with the 12 Gy TBI plans. Significant risk reductions were also found with the TMI plans using the plateau risk model. ConclusionsAt both the 12 Gy and 20 Gy prescription dose levels, a conditioning regimen using TMI could significantly lower overall radiation-induced secondary solid-tumor risks for major organs compared with a conditioning regimen with standard 12 Gy TBI. Clinical data from long-term follow-up studies are needed to verify the model predictions.

Functional Optimization of Radionuclide Pairs in Theranostics of Prostate Cancer

The functional optimization of the composition of radiopharmaceutical pairs based on the prostatespecific membrane antigen (PSMA) for the radionuclide theranostics of castration-resistant prostate cancer was carried out. The analysis of radiation-physical and dosimetric characteristics of 9 radionuclides for diagnostic components of theranostic pairs and 6 radionuclides for therapeutic components is carried out. It was shown that positron-emitting radionuclides 18F and 68Ga should be considered optimal for the diagnosis and monitoring of the effectiveness of theranostics, and 177Lu beta-emitting radionuclide and 225Ac alphabeta-emitting radionuclide should be considered as the radionuclide therapy. The values of the total and organ radiation risks of secondary radiation-induced cancers in patients who have completed several courses of theranostics are calculated. It is shown that for 2 teranostic pairs based on 177Lu‑PSMA the radiation risk is higher than significant, while for 2 teranostic pairs based on 225Ac the risk falls within the range of a significant level. The calculated radiological criteria for discharge of patients after a course of theranostics from nuclear medicine departments show the fundamental possibility of performing an outpatient treatment regimen using any of the 4 considered theranostic pairs.

Comparison of Radiation-Induced Secondary Malignancy Risk Between Sequential and Simultaneous Integrated Boost for the Treatment of Nasopharyngeal Carcinoma: Intensity-Modulated Radiotherapy versus Volumetric-Modulated Arc Therapy.

PurposeThis study aimed to compare the secondary cancer risk (SCR) between the sequential boost (SEQ) technique and simultaneous integrated boost (SIB) technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with nasopharyngeal carcinoma (NPC) using the concepts of organ equivalent dose (OED) and excess absolute risk (EAR).Patients and MethodsIMRT-SEQ, VMAT-SEQ, IMRT-SIB, and VMAT-SIB plans were created with identical objective functions for five patients with early-stage NPC. Three different planning tumor volumes (PTVs; PTV1, PTV2, and PTV3) were delineated for each patient, and the prescribed doses were 50 Gy, 60 Gy, and 70 Gy (2 Gy/fraction), respectively, for the SEQ technique and 52.8 Gy, 59.4 Gy, and 69.3 Gy (33 fractions), respectively, for the SIB technique.ResultsAll plans were clinically acceptable. There was no difference in most OED-based SCRs between IMRT and VMAT when the same fractionation scheme was used. Compared with the SEQ technique, the SIB technique in IMRT and VMAT was associated with the lowest OEDs for the oral cavity, pharynx, parotids, and submandibular glands, resulting in SCR reduction. SCR for the parotids was much lower than that for the other assessed organs when the SIB technique was used.ConclusionOur findings suggest that OED-based SCRs are lower with the SIB technique than with the SEQ technique in IMRT and VMAT in most organs for which SCR was calculated; furthermore, SCR for the parotids is much lower than that for other organs when the SIB technique is used in patients with NPC.