Excess Absolute Risk Research Articles

Long-term and short-term cardiovascular disease mortality among patients of 21 non-metastatic cancers

IntroductionPrevious studies on cardiovascular disease (CVD) death risk in cancer patients mostly focused on overall cancer, age subgroups and single cancers. ObjectivesTo assess the CVD death risk in non-metastatic cancer patients at 21 cancer sites. MethodsA total of 1,672,561 non-metastatic cancer patients from Surveillance, Epidemiology, and End Results (SEER) datebase (1975–2018) were included in this population-based study, with a median follow-up of 12·7 years. The risk of CVD deaths was assessed using proportions, competing-risk regression, absolute excess risks (AERs), and standardized mortality ratios (SMRs). ResultsIn patients with localized cancers, the proportion of CVD death and cumulative mortality from CVD in the high-competing risk group (14 of 21 unique cancers) surpassed that of primary neoplasm after cancer diagnosis. The SMRs and AERs of CVD were found higher in patients with non-metastatic cancer than the general US population (SMR 1·96 [95 %CI, 1·95-1·97]–19·85[95 %CI, 16·69-23·44]; AER 5·77–210·48), heart disease (SMR 1·94[95 %CI, 1·93-1·95]–19·25[95 %CI, 15·76-23·29]; AER 4·36–159·10) and cerebrovascular disease (SMR 2·05[95 %CI, 2·02-2·08]–24·71[95 %CI, 16·28-35·96]; AER 1·01–37·44) deaths. In the high-competing risk group, CVD-related SMR in patients with localized stage cancer increased with survival time but followed a reverse-dipper pattern in the low-competing risk group (7 of 21 cancers). The high-competing risk group had higher CVD-related death risks than the low-competing risk group. ConclusionThe CVD death risk in patients with non-metastatic cancer varied by cancer stage, site and survival time. The risk of CVD mortality is higher in 14 out of 21 localized cancers (high-competing cancers). Targeted strategies for CVD management in non-metastatic cancer patients are needed.

Evaluation of risks of cardiovascular disease from radiation exposure linked to computed tomography scans in the UK

Epidemiological studies of patient populations have shown that high doses of radiation increase risks of cardiovascular disease (CVD). Results from a recent meta-analysis of 93 epidemiological studies covering a wide range of doses provided evidence of a causal association between radiation exposure and CVD, and indicated excess relative risk per Gy for maximum dose below 500 mGy or delivered at low dose rates. These doses cover the range of organ doses expected from multiple diagnostic computed tomography (CT) scans. Dose-effect factors for the excess absolute risk of mortality from CVD following radiation exposure were derived from the meta-analysis. The present study uses these factors to estimate excess risks of mortality for various types of CVD, including cerebrovascular disease (CeVD), from CT scans of the body and head, assuming that the meta-analytic factors were accurate and represented a causal relationship. Estimates are based on cumulative doses to the heart and brain from CT scans performed on 105 574 patients on 12 CT scanners over a period of 5½ years. The results suggest that the excess number of deaths from CeVD could be 7 or 26 per 100 000 patients depending whether threshold brain doses of 200 mGy or 50 mGy, respectively are assumed. These results could have implications for head CT scans. However, the results rely on the validity of risk factors derived in the meta-analysis informing this assessment and which include significant uncertainties. Further incidence studies should provide better information on risk factors and dose thresholds, particularly for CeVD following head CT scans.

Short term exposure to low level ambient fine particulate matter and natural cause, cardiovascular, and respiratory morbidity among US adults with health insurance: case time series study

ObjectiveTo estimate the excess relative and absolute risks of hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease associated with daily exposure to fine particulate...

Radiation Therapy for Stage IIA/B Seminoma: Modeling Secondary Cancer Risk for Protons and VMAT versus 3D Photons.

Radiation therapy (RT) is an effective treatment for stage IIA and select stage IIB seminomas. However, given the long life expectancy of seminoma patients, there are concerns about the risk of secondary cancers from RT. This study assessed differences in secondary cancer risk for stage II seminoma patients following proton pencil-beam scanning (PBS) and photon VMAT, compared to 3D conformal photon RT. Ten seminoma patients, five with a IIA staging who received 30 GyRBE and five with a IIB staging who received 36 GyRBE, had three RT plans generated. Doses to organs at risk (OAR) were evaluated, and secondary cancer risks were calculated as the Excess Absolute Risk (EAR) and Lifetime Attributable Risk (LAR). PBS reduced the mean OAR dose by 60% on average compared to 3D, and reduced the EAR and LAR for all OAR, with the greatest reductions seen for the bowel, liver, and stomach. VMAT reduced high doses but increased the low-dose bath, leading to an increased EAR and LAR for some OAR. PBS provided superior dosimetric sparing of OAR compared to 3D and VMAT in stage II seminoma cases, with models demonstrating that this may reduce secondary cancer risk. Therefore, proton therapy shows the potential to reduce acute and late side effects of RT for this population.

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma.

Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages. We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses. After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]). This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.

Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

Childhood cancer survivors are at increased risk of late mortality (death ≥5years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.

Cause-specific mortality in a population-level cohort of diffuse large B-cell lymphoma following chemotherapy in the early 21st century.

Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed.

Evaluation of organ dose using size-specific dose estimation (SSDE) and related cancer risk due to chest CT scan during the COVID-19 pandemic.

This study aimed to estimate lung and breast doses for individual patients using the size-specific dose estimate (SSDE) method, as well as calculating effective doses, in patients who underwent chest CT scans during the COVID-19 pandemic. Cancer risk incidence was estimated using excess relative risk (ERR), excess absolute risk (EAR), and lifetime attributable risk (LAR) models from the Biological Effects of Ionizing Radiation Report VII (BEIR-VII). Data from about 570 patients who underwent CT scans for COVID-19 screening were utilized for this study. Using the header of the CT images in a Python script, SSDE and effective dose were calculated for each patient. The SSDE obtained by water equivalent effective diameter (wSSDE) was considered as lung and breast dose, and applied in organ-specific cancer risk estimation. The mean wSSDE value for females (13.3mGy) was slightly higher than that for males (13.1mGy), but the difference was not statistically significant (P value=0.41). No significant differences were observed between males and females in terms of calculated EAR and ERR for lung cancer at 5 and 30years after exposure (P value=0.47, 0.46, respectively). Similarly, there was no significant difference in lung cancer LAR values between females and males (P value=0.48). The results also indicated a decrease in LAR values for both lung and breast cancers with increasing exposure age. In accordance with the ALARA (as low as reasonably achievable) principle, it is important for medical staff and the general public to consider the benefits of CT imaging in detecting such infections. Additionally, imaging medical physicists and CT scan experts should optimize imaging protocols and strike a balance between image quality for detecting abnormalities and radiation dose, all while adhering to the ALARA principle.

Incidence and Risk of Secondary Malignancy in Patients with Waldenström Macroglobulinemia: A Population-Based Analysis.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma which may predispose individuals to development of secondary malignancies (SMs). The Surveillance, Epidemiology, and End Results (SEER) database is a comprehensive registry of cancer patients in the United States reporting on a wide set of demographic variables. Using the SEER-18 dataset, analyzing patients from 2000 to 2018, we aimed to assess the incidence of SMs in WM patients. Patient characteristics such as gender, age, race, and latency were identified, and respective standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated to compare to the general population. Of the 4,112 eligible WM patients identified, SMs were reported in 699 (17%) patients. The overall risk of developing SM, second primary malignancy, and secondary hematological malignancy was significantly higher in WM patients compared to the general population. Our findings show that WM patients had a 53% higher risk of SMs relative to the general population, and an AER of 102.69 per 10,000. Although the exact mechanism is unclear, the risk of SM development may be due to genetic predisposition, immune dysregulation, or treatment-induced immune suppression.

Lifetime excess absolute risk for lung cancer due to exposure to radon: results of the pooled uranium miners cohort study PUMA

The Pooled Uranium Miners Analysis (PUMA) study is the largest uranium miners cohort with 119,709 miners, 4.3 million person-years at risk and 7754 lung cancer deaths. Excess relative rate (ERR) estimates for lung cancer mortality per unit of cumulative exposure to radon progeny in working level months (WLM) based on the PUMA study have been reported. The ERR/WLM was modified by attained age, time since exposure or age at exposure, and exposure rate. This pattern was found for the full PUMA cohort and the 1960 + sub-cohort, i.e., miners hired in 1960 or later with chronic low radon exposures and exposure rates. The aim of the present paper is to calculate the lifetime excess absolute risk (LEAR) of lung cancer mortality per WLM using the PUMA risk models, as well as risk models derived in previously published smaller uranium miner studies, some of which are included in PUMA. The same methods were applied for all risk models, i.e., relative risk projection up to <95 years of age, an exposure scenario of 2 WLM per year from age 18–64 years, and baseline mortality rates representing a mixed Euro-American-Asian population. Depending upon the choice of model, the estimated LEAR per WLM are 5.38 × 10−4 or 5.57 × 10−4 in the full PUMA cohort and 7.50 × 10−4 or 7.66 × 10−4 in the PUMA 1960 + sub-cohort, respectively. The LEAR per WLM estimates derived from risk models reported for previously published uranium miners studies range from 2.5 × 10−4 to 9.2 × 10−4. PUMA strengthens knowledge on the radon-related lung cancer LEAR, a useful way to translate models for policy purposes.

Long-term second primary cancer risk in adolescent and young adult (15-39 years) cancer survivors: a population-based study in the Netherlands between 1989 and 2018

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 and2018. 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. 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). 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.

Abstract 17859: Real World Cardiovascular Events With Next Generation Bruton's Tyrosine Kinase Inhibitors - An Updated Analysis

Introduction: Acalabrutinib and zanubrutinib are next generation Bruton’s tyrosine kinase inhibitors (BTKIs) associated with dramatic efficacy against B cell malignancies. In early trials, these BTKIs show less cardiac activity than ibrutinib. Yet, whether this is seen in longer term follow up is unknown. Methods: Leveraging the US Food and Drug Administration’s Adverse Events Reporting System (FAERS), we identified the relative incidence and predictive factors for atrial fibrillation (AF) after BTKI initiation from 2015-2022. Secondary outcomes were the reporting odds ratios (ROR) of major adverse cardiovascular adverse events (AEs), defined as AF, non-AF atrial arrhythmias, heart failure, conduction blocks, and ventricular arrythymias. In addition, using a registry cohort of 838 hematologic malignancy patients treated with ibrutinib or acalabrutinib from 2012-2020, we assessed the comparative incidence of new AF. Observed incident AF rates were compared with Framingham heart predicted rates, and absolute excess risks of AF were estimated. Multivariable logistic-regression models were used to identify factors associated with AF, other cardiac AEs, and mortality. Results: Among 21,435 events reported to FAERS during BTKI use, 3,453 were cardiovascular AEs. AF was the most reported AE (ROR 8.8, 95% CI, 8.3-9.4; Figure A ). The likelihood (ROR) of cardiac AE reporting in next generation BTKI treated patients was &gt;3.0 ( P &lt;0.05; Figure A ) for AF events. Furthermore, in acalabrutinib treated registry patients, 9.7% developed incident AF over a median follow up of 42 months. In those without prior ibrutinib use, the weighted average incidence was 281 per 10,000 person years compared to the Framingham predicted rate of 103 per 10,000 person years (RR 2.73, P &lt;0.001; AER 178; Figure B ). Conclusions: These data suggest residual AF risk with next generation BTKIs.

Association of low-dose ionising radiation with site-specific solid cancers: Chinese medical X-ray workers cohort study, 1950–1995

BackgroundThe dose–response relationship between cancers and protracted low-dose rate exposure to ionising radiation is still uncertain. This study aims to estimate quantified relationships between low-dose radiation exposures and site-specific solid...

Second Hematologic Malignancies Associated With Primary Mediastinal Germ Cell Tumors: A Population-based Study.

Studies addressing second hematologic malignancies (SHMs) in patients with primary mediastinal germ cell tumors (PMGCTs) are scarce. To better describe this phenomenon, we analyzed a large case series from a population-based registry. The Surveillance, Epidemiology, and End Results database was used to report the clinical characteristics and incidence of SHMs in patients with PMGCT. Among 1297 PMGCTs, 27 cases (2.08%) of SHM were found, with a median latency period of 12 months (95% CI: 5-41). All SHM occurred in males, 20 of whom (74.1%) had a previous nonseminomatous tumor. Acute myeloid leukemia was the most frequent SHM, accounting for 13 cases, 4 of which were acute megakaryoblastic leukemia that occurred within 5 months of diagnosis. The median survival after the diagnosis of SHM was 6 months (95% CI: 2-41). The risk of SHM was significantly higher than expected for the reference population, with a standardized incidence ratio of 6.21 (95% CI: 3.31-10.62) and an absolute excess risk of 19.19 per 10,000 person-years. Patients with PMGCT are at a higher risk of developing SHMs than the general population, particularly acute myeloid leukemia. This risk ranges from synchronous diagnosis of acute megakaryoblastic leukemia to the later onset of other hematological disorders that might be related to PMGCT therapies. Our findings may help create follow-up schedules for patients with PMGCT and raise the level of suspicion surrounding this association.

Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes

Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A PENTEC Comprehensive Review

A Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis of published investigations of central nervous system (CNS) subsequent neoplasms (SNs), subsequent sarcomas, and subsequent lung cancers in childhood cancer survivors who received radiation therapy (RT) was performed to estimate the effect of RT dose on the risk of SNs and the modification of this risk by host and treatment factors. A systematic literature review was performed to identify data published from 1975 to 2022 on SNs after prior RT in childhood cancer survivors. After abstract review, usable quantitative and qualitative data were extracted from 83 studies for CNS SNs, 118 for subsequent sarcomas, and 10 for lung SNs with 4 additional studies (3 for CNS SNs and 1 for lung SNs) later added. The incidences of SNs, RT dose, age, sex, primary cancer diagnosis, chemotherapy exposure, and latent time from primary diagnosis to SNs were extracted to assess the factors influencing risk for SNs. The excess relative ratio (ERR) for developing SNs as a function of dose was analyzed using inverse-variance weighted linear regression, and the ERR/Gy was estimated. Excess absolute risks were also calculated. The ERR/Gy for subsequent meningiomas was estimated at 0.44 (95% CI, 0.19-0.68); for malignant CNS neoplasms, 0.15 (95% CI, 0.11-0.18); for sarcomas, 0.045 (95% CI, 0.023-0.067); and for lung cancer, 0.068 (95% CI, 0.03-0.11). Younger age at time of primary diagnosis was associated with higher risk of subsequent meningioma and sarcoma, whereas no significant effect was observed for age at exposure for risk of malignant CNS neoplasm, and insufficient data were available regarding age for lung cancer. Females had a higher risk of subsequent meningioma (odds ratio, 1.46; 95% CI, 1.22-1.76; P < .0001) relative to males, whereas no statistically significant sex difference was seen in risk of malignant CNS neoplasms, sarcoma SNs, or lung SNs. There was an association between chemotherapy receipt (specifically alkylating agents and anthracyclines) and subsequent sarcoma risk, whereas there was no clear association between specific chemotherapeutic agents and risk of CNS SNs and lung SNs. This PENTEC systematic review shows a significant radiation dose-response relationship for CNS SNs, sarcomas, and lung SNs. Given the linear dose response, improved conformality around the target volume that limits the high dose volume might be a promising strategy for reducing the risk of SNs after RT. Other host- and treatment-related factors such as age and chemotherapy play a significant contributory role in the development of SNs and should be considered when estimating the risk of SNs after RT among childhood cancer survivors.

Secondary Cancer Risk of Radiotherapy and Imaging Examination for Two Different Malignancies in One Patient

Purpose: Radiotherapy (RT), which is considered one of the critical treatments for cancer patients is also known as adjuvant therapy and palliative care, and can be attempted alone or concurrent with chemotherapy. Although RT reduces the risk of recurrence, the scattered dose may enhance the risk of secondary cancer induction; this is raising some challenges in clinical practice. To the best of our knowledge, few studies to date have assessed such effects of brain cancer adjuvant radiotherapy.&#x0D; Materials and Methods: We estimated the RT-induced risk of secondary cancer for a 45-year-old patient who had undergone radiotherapy of the head and pelvis with a 6 MV photon beam in 15 and 10 sessions, respectively. The absorbed dose by the thyroid, breast, eye lenses, region overlying ovaries, and parotids was measured using Thermoluminescent Dosimeters (TLD). Since the patient was scanned before radiotherapy, it was decided to calculate their risk as well. To evaluate the cancer risk, radiobiological models for Excess Absolute Risk (EAR), as well as Excess Relative Risk (ERR) published by the Committee on the Biological Effects of Ionizing Radiation (BEIR) in report VII, were implemented. This study thus aimed to estimate the Risk of Exposure-Induced Death (REID) and assess the radiation dose delivered to patients from Computed Tomography (CT) scans and common diagnostic nuclear medicine examinations.&#x0D; Results: The mean risk of secondary cancer for sensitive organs was calculated 3 years after radiotherapy. The highest estimated ERR was related to the region overlying right and left ovaries for pelvic radiotherapy (47.82) and (51.17), and the next highest EAR followed by right and left eye lenses for brain radiotherapy (18.09) and (15.43), respectively. In addition, other cancers arising from CT scans had the highest REID values for solid cancer (0.0015) and bone scans revealed the highest REID values for other cancers (0.00121).&#x0D; Conclusion: Calculating the corresponding risks of RT is of great significance for the patients in procedural change. Choosing proper field sizes and adapted techniques to avoid excessive doses to healthy organs can thus be a great assistance in this regard.

Area Dose-Response and Radiation Origin of Childhood Thyroid Cancer in Fukushima Based on Thyroid Dose in UNSCEAR 2020/2021: High 131I Exposure Comparable to Chernobyl.

The FMU and the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) concluded that the high incidence of thyroid cancer after the Fukushima nuclear accident was not the result of radiation exposure, but rather might have been overdiagnosis based on the low thyroid dose estimated in the UNSCEAR 2020/2021 report. In this study, the origin of increased PTC in Fukushima was examined based on the thyroid dose estimated by UNSCEAR. The dose-response relationship of the incidence rate per person-years (PY) was analyzed for four areas in Fukushima prefecture via regression analysis. The linear response of the annual incidence rates to thyroid dose in the first six years showed that the dominant origin of childhood thyroid cancer was radiation exposure. Excess absolute risk (EAR) proportionally increased with thyroid dose, with an EAR/104 PY Gy of 143 (95%CI: 122, 165) in the second TUE (p < 0.001), which is approximately 50-100 times higher than the EAR/104 PY Gy ≒ 2.3 observed after the Chernobyl accident. This suggests an underestimation of the thyroid dose by UNSCEAR of approximately 1/50~1/100 compared with the thyroid dose for Chernobyl. The increased childhood thyroid cancer in Fukushima was found to arise from radioactive iodine exposure, which was comparable to that in Chernobyl.

Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma

Background Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. Material and methods A comparative treatment planning study was conducted on planning CT-scans from ten patients with stage II seminoma, treated with photons to a ‘dog-leg’ field with doses ranging from 20 to 25 Gy and a 10 Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3–4 field IMRT (Eclipse) or 1–2 arc VMAT (Pinnacle). Proton plans used robust (5 mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. Results Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p < .05) and 0.33 for IMPT/VMAT (p < .05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. Conclusion Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR.

Significant risk of second primary cancer among laryngeal squamous cell carcinoma patients even after 20 years

Background: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. Methods: Patients diagnosed with primary LSCC from 1953–2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included. Results: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n = 1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52–1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19–11). The corresponding SIR for women was 1.47 (95% CI: 1.15–1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36–9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49–2.01 and EAR 16.8 per 1000 PY, 11.88–23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36–3.95 and EAR 0.80 per 1000 PY, 0.55–1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13–6.78). Conclusion: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment.