Association between radiation therapy for primary endometrial cancer and risk of second primary malignancies: a retrospective cohort study.

Our objective was to evaluate the association of adjuvant radiation therapy (RT) to subsequent second primary malignancies (SPMs) in endometrial cancer survivors. Patients with endometrial cancer as their first malignancy were identified from 8 registries of the Surveillance, Epidemiology, and End Results (SEER) database. SPMs were defined as any type of primary malignancy that occurred more than 12 months after the diagnosis of endometrial cancer. Fine-Gray competing risk regression and Poisson regression were used to evaluate the radiotherapy-associated risk (RR) for SPMs. The Kaplan-Meier method was applied to assess the survival outcomes of endometrial cancer patients. Of 62,108 endometrial cancer patients,16,846 patients (27.12%) were in the RT group, and 45,262 patients (72.88%) were in the no-RT group. During the 30-year follow-up period, the cumulative incidence of SPMs was 20.9% and 19.7% in each group, respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, adjuvant RT was found to be associated with a higher risk of developing colon and rectum cancer (adjusted hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.12-1.50; P < 0.001; adjusted RR, 1.29; 95% CI, 1.11-1.49; P < 0.001), lung and bronchus cancer (adjusted HR, 1.27; 95% CI, 1.08-1.50; P = 0.004; adjusted RR, 1.26; 95% CI, 1.07-1.49; P = 0.005), vulva cancer (adjusted HR, 1.72; 95% CI, 1.04-2.85; P = 0.036; adjusted RR, 1.74; 95% CI, 1.03-2.88; P = 0.035), urinary bladder cancer (adjusted HR, 1.86; 95% CI, 1.41-2.46; P < 0.001; adjusted RR, 1.85; 95% CI, 1.40-2.44; P < 0.001), and non-Hodgkin lymphoma (adjusted HR, 1.37; 95% CI, 1.06-1.77; P = 0.016; adjusted RR, 1.37; 95% CI, 1.05-1.76; P = 0.017). However, a slightly decreased risk of breast cancer was observed in patients who underwent adjuvant RT (adjusted HR, 0.89; 95% CI, 0.80-0.98; P = 0.021; adjusted RR, 0.88; 95% CI, 0.80-0.98; P = 0.020). The RR for colon and rectum cancer decreased with age and elevated with increasing latency since endometrial cancer diagnosis, and the RR for urinary bladder cancer showed a similar tendency with latency. SPMs can significantly impair the survival outcomes of primary endometrial cancer survivors. Our findings suggest that adjuvant RT for endometrial cancer patients increases the risk of non-Hodgkin lymphoma and several types of solid cancer. Long-term surveillance of these patients should be recommended for detecting SPMs.

Proton beam therapy in a patient with secondary glioblastoma (32 years after postoperative irradiation of medulloblastoma): case report and literature review.

OBJECTIVE: This report details the experience of a patient who developed a second primary glioblastoma (GB), offering insights into the treatment process and reviewing relevant literature. CASE PRESENTATION: A male patient, who was diagnosed with medulloblastoma at age 9, received treatment with cobalt-60 craniospinal irradiation (CSI) (36 Gy/20 fractions) and a tumor bed boost (total of 56 Gy). After 32 years, at age 41, an MRI revealed a space-occupying mass in the left cerebellar hemisphere. Surgical resection was performed, and postoperative pathology confirmed a diagnosis of radiation-induced glioblastoma (RIGB). Given the history of irradiation and the current tolerability of brainstem doses, proton beam therapy (PBT) combined with Temozolomide (75 mg/m2) was chosen. The treatment plan included 60 Gy on the gross tumor bed and 54 Gy on the clinical target volume, delivered in 30 fractions. The patient underwent regular follow-up and achieved a complete response. CLINICAL DISCUSSION: For childhood cancer survivors, the development of a second primary tumor significantly impacts prognosis. RIGB is a rare form of secondary tumor with distinct molecular characteristics compared to primary GB and recurrent secondary GB. Molecular markers such as IDH and MGMT status can help differentiate between primary GB, recurrent secondary GB, and radiation-induced secondary GB in patients with a history of prior radiation therapy. Surgical resection remains a primary treatment option, while PBT is preferred for postoperative treatment due to its superior protection of normal tissues and the ability to deliver high-dose irradiation. CONCLUSION: RIGB is a rare second primary tumor that requires strategic molecular profiling and individualized management. Proton beam therapy provides effective high-dose irradiation in the postoperative phase and is the preferred treatment option for such cases.

AB051. Multiple meningiomas developed outside the radiation field after cranial irradiation: a case report.

BACKGROUND: Cranial irradiation has well-known long-term side effects, including radiation-induced neoplasms and vasculopathy. This report describes a case of aggressive and rapid-growing multiple meningiomas developed outside the radiation field after the treatment of medulloblastoma. CASE DESCRIPTION: A 6-year-old boy underwent surgery (gross total resection) and radiotherapy (19.8 Gy for posterior fossa only) against medulloblastoma in the 4th ventricle. The patient could not receive further craniospinal irradiation because of ventriculoperitoneal shunt-related complications. Eighteen years after the radiotherapy, the first meningioma developed in the right temporal convexity, without recurrence of medulloblastoma. It was left untreated because it was asymptomatic. Three years later, the meningioma grew from 0.6 to 6.3 cm3 in volume and another large meningioma (22.1 cm3) developed in the left temporal convexity with additional small meningioma in the right frontal convexity. The left large temporal meningioma showed aggressive nature invading the adjacent temporal bone and temporalis muscle. It was completely resected and the histology revealed as transitional meningioma with 2% of Ki-67. Another new meningioma was identified on the right cerebellar convexity three years post-craniotomy. Subsequent follow-up indicated a progressive increase in the tumor size and gamma knife radiosurgery was performed with right frontal convexity small meningioma. The patient is currently under ongoing surveillance through follow-up assessments. CONCLUSIONS: For patients who received radiotherapy at a young age, clinicians should consider the possibility of secondary neoplasm development even outside the radiation field. Careful imaging follow-up and surgical management are warranted because of the aggressive nature of secondary tumors even though benign in histology.

Radiation-Induced Childhood Thyroid Cancer after the Fukushima Daiichi Nuclear Power Plant Accident.

After the Fukushima Nuclear Power Plant accident in March 2011, a large-scale ultrasound examination of childhood thyroid cancer for all Fukushima residents aged 18 years old or younger was initiated. Fukushima was divided into four areas according to the external radioactivity released by the accident: the highest (A), high-intermediate (B), low-intermediate (C), and the lowest (D). Five rounds of surveys were carried out from October 2011 to March 2023. The annual incidence rates of the "Common Case" not affected by the accident were able to be estimated. The difference between the incidence rate of whole patients and the "Common Case" is that of the "Radiation-induced Case". The annual incidence rate of the "Radiation-induced Case" began to increase immediately after the accident, where the highest level was seen in A area, and the order was A > B > C > D. It showed that the development of childhood thyroid cancer was affected by the radiation released by the accident. The effect of the radiation consisted of two phases: the first phase may have been due to the damage to the immune system, and the second phase may have been due to the genetic mutation in the children who were youngest at the time of the accident.

Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study.

BACKGROUND: A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. METHODS: We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. FINDINGS: The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. INTERPRETATION: This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. FUNDING: National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Development of Melanoma and Other Nonkeratinocyte Skin Cancers After Thyroid Cancer Radiation.

This cohort study evaluates the association between thyroid malignant neoplasms and melanoma and other nonkeratinocyte skin cancers.

Utilizing patient data: A tutorial on predicting second cancer with machine learning models.

BACKGROUND: The article explores the potential risk of secondary cancer (SC) due to radiation therapy (RT) and highlights the necessity for new modeling techniques to mitigate this risk. METHODS: By employing machine learning (ML) models, specifically decision trees, in the research process, a practical framework is established for forecasting the occurrence of SC using patient data. RESULTS & DISCUSSION: This framework aids in categorizing patients into high-risk or low-risk groups, thereby enabling personalized treatment plans and interventions. The paper also underscores the many factors that contribute to the likelihood of SC, such as radiation dosage, patient age, and genetic predisposition, while emphasizing the limitations of current models in encompassing all relevant parameters. These limitations arise from the non-linear dependencies between variables and the failure to consider factors such as genetics, hormones, lifestyle, radiation from secondary particles, and imaging dosage. To instruct and assess ML models for predicting the occurrence of SC based on patient data, the paper utilizes a dataset consisting of instances and attributes. CONCLUSION: The practical implications of this research lie in enhancing our understanding and prediction of SC following RT, facilitating personalized treatment approaches, and establishing a framework for leveraging patient data within the realm of ML models.

Cancer Incidence in a Population Living Near Radioactive Waste Storage of Uranium Mining in Stepnogorsk Area, Northern Kazakhstan.

OBJECTIVE: This study evaluates the impact of radioactive uranium waste storage facilities on cancer occurrence in nearby areas. METHODS: Current research evaluates the effect of radioactive uranium waste storage facilities on cancer epidemiology in nearby areas. The critical area had Aqsu, Kvartsitka, Zavodskoy and Stepnogorsk cities, which are located at a less than 5 km distance to the south of the Hydrometallurgical Plant tailings dump while the control group had Akkol region in 90 km from the source. The majority of population had lived in this territory more than the 30 years. Data were obtained from the Electronic Register of Cancer Patients of the Republic of Kazakhstan from 2001-2015, and 2,271 incident cases of cancer were registered. RESULTS: The most frequent malignancies were observed in the digestive organs (646 cases, 28%) and respiratory and intrathoracic organs (376 cases, 17%). The proportion of digestive organ cancers was higher in the critical group (560 cases out of 1913, 29%) than in the control group (86 cases out of 358, 24%). Additionally, respiratory organ cancers were more common in men, but the cancer incidence rate ratio was higher in the critical area. Notably, the study found that the cancer incidence rate ratios decreased over time, specifically for digestive, respiratory and female genital organs and breast cancer. CONCLUSION: In conclusion, while our study highlights significant differences in cancer incidence rates and frequencies between the critical and control groups, further analytical research, incorporating age-adjustment, is needed to provide a more conclusive evaluation of the potential impact of residence in proximity to the uranium mining waste storage on cancer occurrence in the study area.

Uranium in Drinking Water and Bladder Cancer: A Case-control Study in Michigan.

ABSTRACT: Uranium is naturally occurring in groundwater used for drinking; however, health risks from naturally occurring concentrations are uncertain. Uranium can cause both radiological and chemical toxicity following ingestion. Bladder and kidneys receive a dose when uranium is excreted into the urine. Investigate the association between uranium in drinking water and bladder cancer risk in a case-control study. A population-based bladder cancer case-control study was conducted in 11 counties of southeastern Michigan. A total of 411 cases and 566 controls provided drinking water and toenail samples and answered questions about lifestyle and residential history. Uranium was measured in drinking water and toenails, and its association with bladder cancer was assessed via unconditional logistic regression models. Median uranium concentration in water was 0.12 µg L -1 , with a maximum of 4.99 µg L -1 , and median uranium concentration in toenails was 0.0031 µg g -1 . In adjusted regression models, there was a suggestion of a protective effect among those exposed to the upper quartile of uranium in drinking water (HR = 0.64, 95% CI: 0.43, 0.96) and toenails (HR 0.66; 95% CI 0.45, 0.96) compared to those in the lowest quartile. Our objective is to investigate additional adjustment of drinking water source at home residence at time of recruitment to address potential selection bias and confounding attenuated results toward the null for drinking water uranium (HR = 0.68, 95% CI: 0.44, 1.05) and toenail uranium (HR = 0.80, 95% CI: 0.53, 1.20). This case-control study showed no increased risk of bladder cancer associated with uranium found in drinking water or toenails.

Dose Reconstruction for Epidemiological Studies among Ukrainian Chernobyl Cleanup Workers.

The present paper provides an overview of the methods and summarizes the results of estimating radiation doses and their uncertainties for Ukrainian-American epidemiological studies among the Chernobyl (Chornobyl) cleanup workers. After the Chernobyl accident occurred on April 26, 1986, more than 300,000 Ukrainian cleanup workers took part between 1986 and 1990 in decontamination and recovery activities at the site of the Chernobyl Nuclear Power Plant. The U.S. National Cancer Institute in collaboration with the Ukrainian National Research Center for Radiation Medicine conducted several epidemiological studies in this population. An important part of these studies was the reconstruction of the study participants' radiation doses and the assessment of uncertainties in doses. A method called realistic analytical dose reconstruction with uncertainty estimation (RADRUE) was used to calculate the doses from external irradiation during cleanup missions, which was the main exposure pathway for most study participants. At the initial phase of the accident during the atmospheric releases of radioactivity from the destroyed reactor, the cleanup workers also received doses from inhalation of radionuclides. In addition, study participants received doses at their places of residence, especially those who lived in highly contaminated areas. The radiation doses estimated for 2,048 male cleanup workers included in the Ukrainian-American epidemiological studies varied widely: (i) bone-marrow doses from external irradiation in the case-control study of leukemia of 1,000 cleanup workers ranged from 3.7 × 10-5 mGy to 3.3 Gy (mean = 92 mGy); (ii) thyroid doses in the case-control study of thyroid cancer in 607 persons from all exposure pathways combined were from 0.15 mGy to 9.0 Gy (mean = 199 mGy); (iii) gonadal doses in 183 cleanup workers from all exposure pathways combined in the study of germline mutations in the offspring after parental irradiation (trio study) ranged from 0.58 mGy to 4.1 Gy (mean = 392 mGy); (iv) thyroid doses in the human factor uncertainties study among 47 persons were from 20 mGy to 2.1 Gy (mean = 295 mGy); and (v) lung doses in the study of germline genetic variants associated with host susceptibility to COVID-19 estimated for 211 cleanup workers were from 0.024 mGy to 2.5 Gy (mean = 249 mGy). Doses of female cleanup workers were much lower than those of male cleanup workers: the mean doses for female cleanup workers were 27 mGy for 34 women included in the trio study and 56 mGy for 48 women participated in the study of germline genetic variants associated with host susceptibility to COVID-19. Uncertainties in dose estimates included two components: (i) inherent uncertainties arising from the stochastic random variability of the parameters used in exposure assessment and from a lack of knowledge about the true values of the parameters; and (ii) human factor uncertainties due to poor memory recall resulting in incomplete, inaccurate, or missing responses during personal interviews with cleanup workers conducted long after exposure. This paper also discusses possible developments and improvements in the methods to assess the radiation doses and associated uncertainties for cleanup workers.

[Translated article] Changes in the Location of Cutaneous Melanoma Over the Past 30 Years. A Retrospective Observational Study.

BACKGROUND: The location of cutaneous melanoma is associated with photoexposure. OBJECTIVES: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years. PATIENTS AND METHODS: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017. RESULTS: A total of 1,937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p <0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p <0.001), and in the trunk men (57.5% vs 47.3%, p=0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant. CONCLUSION: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes.

Practical guidance on the assessment of radiation risks for diagnostic radiological examinations.

Patient doses cannot be limited; instead, radiological examinations should be justified and optimised to ensure the necessary diagnostic or therapeutic effect with the lowest patient dose achievable. Assessment of the radiation risks from patient exposure is important part of the justification process. Hence, medical staff within the framework of their professional activities should possess necessary information on the data on radiation risk from different types of radiological procedures. An approach has been developed that allows considering age and gender dependences of the risk coefficients of radiogenic cancer and the age and gender distribution of patients for various radiological examinations to assess the individual radiation risk for patient and collective risk for population from medical exposure. The approach is based on a new expanded use of the effective dose concept proposed in ICRP Publication 147 and demonstrated using the medical exposure in the Russian Federation as the example. For 30 radiological examinations that compose about 80% of the collective dose from medical exposure of the public in the Russian Federation radiation risk was assessed based on calculated age and gender specific risk coefficients per unit effective dose. For the rest of the examinations a simplified approach was used to assess the risk, which was based on using an age and gender specific risk coefficient determined for one of 4 anatomical regions (head, neck, chest and abdomen) or for uniform irradiation of the whole body. The proposed approach allows significantly improving the assessment of the radiation risk while continuing to use the effective dose as a dosimetric quantity within the framework of the state program in the Russian Federation. As a result the collective risk from medical examinations in the Russian Federation in 2022 was lower by the factor of 3 compared to the previous assessment based on the effective dose with the nominal risk coefficient.

Treatment of secondary uterine malignancy following radiotherapy for cervical cancer: a study based on the SEER database.

BACKGROUND: Radiotherapy is one of the main treatments for cervical cancer. Long-term complications of radiation exposure include the emergence of secondary tumors. This is a retrospective study based on an American population. We discuss the optimal treatment modality for patients with radiation-induced secondary uterine malignancy based on the Surveillance, Epidemiology, and End Results database. METHODS: The study included patients with a definitive pathological diagnosis of cervical cancer who were diagnosed with a uterine malignant tumor ≥ 1 year later. Patients in whom cervical cancer was not the first tumor or patients with missing data were excluded. Univariate and multivariate analyses were performed using the COX regression model to screen independent prognostic factors affecting overall survival. Kaplan-Meier survival curves were analyzed using the R software package. RESULTS: We screened 142 patients with a secondary uterine malignancy after cervical cancer treatment, 115 patients with a secondary uterine malignancy after radiotherapy, and 27 patients with a secondary uterine malignancy who did not receive radiotherapy. The average latency period for developing a secondary tumor was 8 years, and 57.04% of the patients had a second tumor at ≥ 60 years of age. In patients with a secondary uterine malignancy after radiotherapy, surgery improved the prognosis [hazard ratio (HR), 0.374; 95% confidence interval (CI), 0.229-0.612], whereas radiotherapy and chemotherapy did not reduce the risk of death. In the subgroup analysis, the surgery plus chemotherapy group had a significantly better survival prognosis than the other groups (HR, 0.251; 95% CI, 0.122-0.515). CONCLUSIONS: The results suggest that the treatment modality in patients with secondary uterine malignancy after radiotherapy for cervical cancer has a significant impact on survival. The survival outcomes of patients receiving surgery combined with chemotherapy are superior to those of patients receiving other treatments.

Bone Radiation-Induced Sarcomas: Outcomes Based on Histology and Surgical Treatment: A Systematic Review of the Literature.

BACKGROUND: Bone radiation-induced sarcomas (B-RIS) are secondary neoplasms with reportedly worse overall survival than de novo bone sarcoma. Treatment strategy for these neoplasms remains uncertain. Our systematic review sought to assess overall survival based on histology and surgical intervention. METHODS: A systemic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO (438415). Studies describing oncologic outcomes of patients with B-RIS in the appendicular and axial skeleton were included. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for quality assessment. Survival analysis by histologic subtype and surgery type was performed in a subset of 234 patients from 11 articles with individualized data. A total of 20 articles with a total of 566 patients were included. The most frequent location was the pelvis (27.7%), and the main histological types were osteosarcoma (69.4%), undifferentiated pleomorphic sarcoma (14.1%), and fibrosarcoma (9.2%). Limb-salvage and amputation were performed in 68.5% and 31.5% of cases, respectively. RESULTS: Local recurrence was 13%, without difference between limb-salvage surgery and amputation (p = 0.51). The metastasis rate was 42.3%. Five-year OS was 43.7% (95% confidence interval [CI], 33.3%-53.5%) for osteosarcoma, 31.5% (95% CI, 11.3%-54.2%) for UPS, and 28.1% (95% CI, 10.6%-48.8%) for fibrosarcoma. Five-year OS was 49.2% (95% CI, 35.3%-61.6%) for limb-salvage and 46.9% (95% CI, 29.1%-62.9%) for amputation. There was no difference in 5-year OS between histologic subtypes (p = 0.18) or treatment type (p = 0.86). CONCLUSION: B-RIS demonstrated poor OS at 5 years after initial management regardless of histology. Limb-salvage surgery was not associated with lower 5-year OS compared with amputation. Future studies should compare both groups while controlling for confounders. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Low Radiation Doses in Oncocytic Lesions of the Parotid Gland: A Double-edged Sword. A Comprehensive Review.

Oncocytic lesions represent a group of benign and potentially precancerous tumors characterized by the accumulation of oncocytes, which are large, granular, and eosinophilic cells. Diagnosing oncocytic lesions in the parotid gland typically involves a combination of imaging techniques, such as ultrasound, Computed Tomography (CT) scans, and Magnetic Resonance Imaging (MRI). Fine-needle aspiration (FNA) biopsy with histopathological examination remains the primary diagnostic tool for these lesions. Accurate diagnosis is crucial for appropriate management decisions. Treatment options for oncocytic lesions in the parotid gland include surgery, conservative management, and radiation therapy (RT). However, in the head and neck region, radiation doses can be a double-edged sword. While RT is a treatment modality, low radiation doses can promote the development of oncocytic lesions in the parotid gland. The prognosis for patients with oncocytic lesions is generally favorable, especially when the lesions are benign and appropriately managed. Current research focuses on the molecular mechanisms underlying oncocytic lesions in response to low-dose radiation exposure. The development of these lesions following low radiation doses represents a significant clinical concern. This manuscript provides a comprehensive overview of the current knowledge regarding oncocytic lesions in the parotid gland, including risk factors, diagnosis, treatment options, and ongoing research, offering valuable insights for clinicians and researchers.

On the informative value of community-based indoor radon values in relation to lung cancer.

BACKGROUND: Radon is a radioactive gas and a major risk factor for lung cancer (LC). METHODS: We investigated the dose-response relationship between radon and LC risk in the International Lung Cancer Consortium with 8927 cases and 5562 controls from Europe, North America, and Israel, conducted between 1992 and 2016. Spatial indoor radon exposure in the residential area (sIR) obtained from national surveys was linked to the participants' residential geolocation. Parametric linear and spline functions were fitted within a logistic regression framework. RESULTS: We observed a non-linear spatial-dose response relationship for sIR < 200 Bq/m3. The lowest risk was observed for areas of mean exposure of 58 Bq/m3 (95% CI: 56.1-59.2 Bq/m3). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m3 (OR = 1.31, 95% CI: 1.01-1.59) as in areas with a mean of 100 Bq/m3 (OR = 1.34, 95% CI: 1.20-1.45). The strongest association was observed for small cell lung cancer and the weakest for squamous cell carcinoma. A stronger association was also observed in men, but only at higher exposure levels. The non-linear association is primarily observed among the younger population (age < 69 years), but not in the older population, which can potentially represent different biological radiation responses. CONCLUSIONS: The sIR is useful as proxy of individual radon exposure in epidemiological studies on lung cancer. The usual assumption of a linear, no-threshold dose-response relationship, as can be made for individual radon exposures, may not be optimal for sIR values of less than 200 Bq/m3.

Radiation exposure of the glandular mammary tissue in women patients with mediastinal Hodgkin lymphoma treated with protons.

PURPOSE: Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. MATERIALS AND METHODS: Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization ("clinical organ at risk"). The glandular tissue ("glandular organ at risk") was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between -80HU and 500HU. RESULTS: The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. CONCLUSION: Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients.

Secondary cancer risk in six anatomical sites when using PAT, IMPT, and VMAT/IMRT radiotherapy.

BACKGROUND AND PURPOSE: Compared to intensity modulated proton therapy (IMPT), proton arc therapy (PAT) is expected to improve dose conformality, delivery efficiency, and provide a more favorable LET distribution. Alternatively, the low-dose bath is potentially spread over larger volumes, which could impact the likelihood of developing a radiation-induced, secondary cancer (SC). The goal of this study was to evaluate this risk in several anatomical sites using newly developed commercial tools. MATERIALS AND METHODS: Treatment plans encompassing six anatomical sites, five patients per site, and three techniques per patient were created using RayStation. Techniques included PAT and IMPT for protons, and either volumetrically modulated radiotherapy (VMAT) or intensity modulated radiotherapy (IMRT) for photons. Risk estimates were based on the organ-equivalent dose (OED) concept using both Schneider's mechanistic dose-response model for carcinoma induction and a linear dose-response model. RESULTS: With few exceptions, mean and integral dose were lowest with PAT. For protons, the factor OEDIMPT/OEDPAT ranged from 0.7 to 1.8 with both the mechanistic and linear model, while for photons OEDphoton/OEDPAT ranged from 1.5 to 10 using the mechanistic model and 1.3 to using the linear model. A strong correlation was found between mean dose and OED for organs with significant repopulation/repair (high R value) and less cell death from single hit interactions (low α value). CONCLUSION: Based on results from both mechanistic and linear risk models, the transition from IMPT to PAT should not substantially affect SC risk in patients treated with proton therapy. Additionally, when using Schneider's model, the shapes of the dose-response curves can be used as a good predictor of how SC risk will respond to shifts from intermediate dose to low dose as anticipated when moving from IMPT to PAT.

A framework for in-field and out-of-field patient specific secondary cancer risk estimates from treatment plans using the TOPAS Monte Carlo system.

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.