COVID-19 and cancer risk arising from ionizing radiation exposure through CT scans: a cross-sectional study.

BACKGROUND: The surge in the utilization of CT scans for COVID-19 diagnosis and monitoring during the pandemic is undeniable. This increase has brought to the forefront concerns about the potential long-term health consequences, especially radiation-induced cancer risk. This study aimed to quantify the potential cancer risk associated with CT scans performed for COVID-19 detection. METHODS: In this cross-sectional study data from a total of 561 patients, who were referred to the radiology center at Imam Hossein Hospital in Shahroud, was collected. CT scan reports were categorized into three groups based on the radiologist's interpretation. The BEIR VII model was employed to estimate the risk of radiation-induced cancer. RESULTS: Among the 561 patients, 299 (53.3%) were males and the average age of the patients was 49.61 ± 18.73 years. Of the CT scans, 408 (72.7%) were reported as normal. The average age of patients with normal, abnormal, and potentially abnormal CT scans was 47.57 ± 19.06, 54.80 ± 16.70, and 58.14 ± 16.60 years, respectively (p-value < 0.001). The average effective dose was 1.89 ± 0.21 mSv, with 1.76 ± 0.11 mSv for males and 2.05 ± 0.29 mSv for females (p-value < 0.001). The average risk of lung cancer was 3.84 ± 1.19 and 9.73 ± 3.27 cases per 100,000 patients for males and females, respectively. The average LAR for all cancer types was 10.30 ± 6.03 cases per 100,000 patients. CONCLUSIONS: This study highlights the critical issue of increased CT scan usage for COVID-19 diagnosis and the potential long-term consequences, especially the risk of cancer incidence. Healthcare policies should be prepared to address this potential rise in cancer incidence and the utilization of CT scans should be restricted to cases where laboratory tests are not readily available or when clinical symptoms are severe.

Secondary meningioma after cranial irradiation: case series and comprehensive literature review.

BACKGROUND: Secondary meningioma after cranial irradiation, so-called radiation-induced meningioma, is one of the important late effects after cranial radiation therapy. In this report, we analyzed our case series of secondary meningioma after cranial irradiation and conducted a critical review of literature to reveal the characteristics of secondary meningioma. MATERIALS AND METHODS: We performed a comprehensive literature review by using Pubmed, MEDLINE and Google scholar databases and investigated pathologically confirmed individual cases. In our institute, we found pathologically diagnosed seven cases with secondary meningioma between 2000 and 2018. Totally, 364 cases were analyzed based on gender, WHO grade, radiation dose, chemotherapy. The latency years from irradiation to development of secondary meningioma were analyzed with Kaplan-Meier analysis. Spearman's correlation test was used to determine the relationship between age at irradiation and the latency years. RESULTS: The mean age at secondary meningioma development was 35.6 ± 15.7 years and the mean latency periods were 22.6 ± 12.1 years. The latency periods from irradiation to the development of secondary meningioma are significantly shorter in higher WHO grade group (P = 0.0026, generalized Wilcoxon test), higher radiation dose group (P < 0.0001) and concomitant systemic chemotherapy group (P = 0.0003). Age at irradiation was negatively associated with the latency periods (r = -0.23231, P < 0.0001, Spearman's correlation test). CONCLUSION: Cranial irradiation at older ages, at higher doses and concomitant chemotherapy was associated with a shorter latency period to develop secondary meningiomas. However, even low-dose irradiation can cause secondary meningiomas after a long latency period. Long-term follow-up is necessary to minimize the morbidity and mortality caused by secondary meningioma after cranial irradiation.

Contemporary diagnostic approach to atypical vascular lesion and angiosarcoma.

Vascular neoplasms account for a substantial fraction of cutaneous mesenchymal tumors, spanning from clinically indolent benign lesions to highly aggressive malignancies. These neoplasms present a distinctive challenge in terms of their diagnostic histopathology, both because of the breadth of their morphological manifestations and because of the significant histological overlap between different entities, even benign and malignant ones. The post-radiotherapy setting is particularly problematic diagnostically, insofar as radiation exposure predisposes not only to secondary angiosarcoma, but also to atypical vascular lesion, a largely benign proliferation of cutaneous blood vessels typically affecting the breast. To address these challenges, we explore the clinical, histological, and molecular features of malignant vascular neoplasia, including primary and secondary subtypes, through the comparative lens of atypical vascular lesion. In addition to highlighting the key morphological indicators of malignancy in superficial vasoformative tumors, we offer an approach that integrates clinical characteristics and molecular genetic profiling to facilitate accurate classification. With this current knowledge as our foundation, we also look ahead in an effort to frame some of the key unanswered questions regarding superficial vascular malignancies and their natural history, clinical management, and molecular underpinnings.

Increased Screening Rates for Thyroid Cancer Among Residents Living Near Nuclear Power Plants.

Frequent screening for thyroid cancer has been suggested as a probable explanation for the observed high risk of thyroid cancer in nuclear power plant (NPP) areas. We aimed to compare thyroid cancer screening rates of residents living near NPPs to those of the general population. This study utilized data from two national survey-based studies in 2016 and in 2014, respectively, for residents (n = 1,200) living in administrative districts within 5 km of NPP sites as the interest group, and the general population (n = 228,712) including distant-living residents (n = 19,100) in administrative districts within 30 km of NPP sites as reference groups. We observed an increase in screening rates in residents near NPPs, which may lead to a higher possibility of thyroid cancer detection. Therefore, further epidemiological studies investigating radiation-induced thyroid cancer risk among residents near NPPs should be carefully designed and interpreted considering possible detection bias.

Young people's perspectives of thyroid cancer screening and its harms after the nuclear accident in Fukushima Prefecture: a questionnaire survey indicating opt-out screening strategy of the thyroid examination as an ethical issue.

BACKGROUND: Overdiagnosis of thyroid cancer has become a major global medical issue. Ultrasound-based thyroid cancer screening has promoted overdiagnosis, and recently international recommendations state that it should not be conducted, even after a nuclear accident. The Fukushima thyroid cancer screening program was initiated in 2011 as a health policy after the nuclear accident. The risk of radiation-induced thyroid cancer was unlikely given the low radiation levels, but the thyroid cancer screening program has continued at 2-year intervals with a relatively high participation rate and is now in its fifth round. It is therefore crucial to clarify whether those targeted for screening understand the disadvantages of screening, and to identify factors that influenced their decision to participate. METHODS: We conducted an anonymous mail-based questionnaire among young people from Fukushima Prefecture (subjects) and a neighboring prefecture that was not targeted for screening (non-subjects). We asked them about the significance of the thyroid cancer screening in Fukushima Prefecture, their reasons for accepting or refusing screening, their perception of the harms of screening, and their opinions on thyroid examination at school. We compared the results of the questionnaire between subjects and non-subjects and between examinees (who were screened) and non-examinees (who declined screening). RESULTS: Only 16.5% of respondents were aware of the harms associated with thyroid cancer screening, with most perceiving that the benefits outweighed the harms. Comparison of subjects' and non-subjects' responses showed there were no significant differences between the two groups. Among subjects, there were also no differences in responses between examinees and non-examinees. The most common reason for participation in screening was that the screening was conducted in schools and perceived as obligatory. CONCLUSIONS: These results highlighted a serious ethical issue in that school-based screening leads to making young people think that it is mandatory screening in an opt-out and default setting manner, with a lack of knowledge about the disadvantages of screening. Based on the autonomy of the subjects and the ethical principle of the post-disaster, surveys after a nuclear disaster should be conducted in an opt-in style without an opt-out style such as school-based screening.

Non-Hodgkin lymphomas and ionizing radiation: case report and review of the literature.

Non-Hodgkin lymphoma (NHL) increased continuously since the last century in developed countries. While they are considered as disease in elder ages, a remarkable increasing incidence is also observed in German children and juveniles. The higher rates are interpreted by the changes in classification because diseases such as chronic lymphocytic leukaemia were also identified as NHL. Considerable rates of NHL were found in nuclear workers and liquidators of Chernobyl, i.e. in cases of low-dose chronical exposures. In Germany, we noticed three workers who developed NHL after decontamination of nuclear facilities. The bone marrow is generally considered as target organ for ionizing radiation, but NHL is obviously induced in the whole pool of lymphocytes. Therefore, the dosimetry in cases of typical occupational external and internal exposure must be revised. A high radiation sensitivity for NHL is a possible suspect and likely reason which may partly explain the continuous rise of the diseases in populations underlying the current increases of medical diagnostic exposure. NHL is also induced in children and juveniles with a history of diagnostic X-rays.

Cranial Irradiation for Childhood Cancers and Adult Risk of Meningioma.

INTRODUCTION: Following cranial irradiation, there is an increased risk of developing secondary neoplasms, especially meningiomas. Despite childhood cancer survivors who have undergone cranial irradiation having an increased risk of acquiring radiation-induced meningioma (RIM), there is no widely used standard guideline for meningioma screening. METHODS: At a single institution, we reviewed three adult survivors of childhood cancer who were treated for RIM between 2010 and 2020. We recorded age at diagnosis for the primary lesion, the radiation dose, age at RIM diagnosis, and tumor characteristics including treatment, pathology, and outcome. Two had had T-cell acute lymphocytic leukemia and one a rhabdomyosarcoma. The age of diagnosis of the RIM ranged from 20 to 40 years, with latencies ranging from 18 to 33 years. All lesions were classified as WHO Grade I meningiomas, and only 1 patient had a subsequent recurrence. A literature search identified articles that address RIM: a total of 684 cases were identified in 36 publications. RESULTS: Mean radiation doses ranged from 1.4 gray to 70 gray. Mean age of diagnosis for secondary meningioma ranged from 8 to 53.4 years old, with latency periods ranging from 2.8 to 44 years. Given variability in the way that investigators have published their results, it is difficult to make a single recommendation for RIM screening. Using our experience and the literature, we devised two different screening protocols and calculated their expense. CONCLUSIONS: We recommend that data be standardized in a registry to provide greater insight into the clinical and resource allocation questions, especially as long-term survival of children with pediatric cancer into full adulthood becomes more commonplace worldwide.

Breast cancer incidence in the regions of Belarus and Ukraine most contaminated by the Chernobyl accident: 1978 to 2016.

Even 30 years after the accident, an association between breast cancer incidence and ionizing radiation exposure from Chernobyl fallout remains uncertain. We studied breast cancer incidence in the most contaminated regions of Belarus (Gomel and Mogilev) and Ukraine (Kyiv, Zhytomyr and Chernihiv) before (1978-1986) and after (1987-2016) the accident. Breast cancer cases and female population size data were received from the national cancer registries and the state departments of statistics. The study included 85 132 breast cancers with 150 million person-years at risk. We estimated annual rayon (district)-average absorbed doses to the breast from external and internal irradiation of the adult female population over the period of 1986-2016. We studied an association between rayon-average cumulative absorbed breast dose with 5-year lag, that is, excluding the exposure in 5 years prior to breast cancer diagnosis, and breast cancer incidence using negative binomial regression models. Mean (median) cumulative breast dose in 2016 was 12.3 (5.0) milligray (mGy) in Belarus and 5.7 (2.3) mGy in Ukraine, with the maximum dose of 55 mGy and 54 mGy, respectively. Breast cancer incidence rates statistically significantly increased with calendar year and attained age, and were higher in urban than in rural residents. Adjusting for time, age and urbanicity effects, we found no evidence of increasing incidence with rayon-average 5-year lagged cumulative breast dose. Owing to ecological study design limitations, a case-control study covering this area with individually reconstructed absorbed breast doses is needed testing for association between low-dose protracted radiation exposure and breast cancer risk after Chernobyl.

Radiation-associated sarcomas other than malignant peripheral nerve sheath tumours demonstrate loss of histone H3K27 trimethylation†.

BACKGROUND AND AIMS: Complete loss of histone H3 lysine 27 trimethylation (H3K27me3) has recently emerged as a biomarker for malignant peripheral nerve sheath tumours (MPNST). Loss of H3K27me3 staining has also been reported in post-radiation MPNST; however, it has not been evaluated in a large series of radiation-associated sarcomas of different histological subtypes. The aim of this study was to assess H3K27me3 labelling by immunohistochemistry in radiation-associated sarcomas and to determine the prevalence of H3K27me3 loss in these tumours. METHODS AND RESULTS: Radiation-associated sarcomas (n = 119) from two tertiary care referral centres were evaluated for loss of H3K27me3, defined as complete loss of staining within tumour cells in the presence of a positive internal control. Twenty-three cases (19%) showed H3K27me3 loss, including nine of 10 (90%) MPNST, seven of 77 (9%) undifferentiated spindle cell/pleomorphic sarcomas, five of 25 (20%) angiosarcomas, one of five (20%) leiomyosarcomas and one of two (50%) osteosarcomas. CONCLUSIONS: Complete H3K27me3 loss was present in 19% of radiation-associated sarcomas in our series. Our findings demonstrate that loss of H3K27me3 is not specific for radiation-associated MPNST and may also occur in other histological subtypes of RAS, including radiation-associated undifferentiated spindle cell/pleomorphic sarcoma, angiosarcoma, leiomyosarcoma and osteosarcoma.

MYC gene amplification by fluorescence in situ hybridization and MYC protein expression by immunohistochemistry in the diagnosis of cutaneous angiosarcoma: Systematic review and appropriate use criteria.

BACKGROUND: Secondary angiosarcoma (AS) most commonly follows breast cancer and includes postirradiation AS (PRAS) and lymphedema-associated AS. The frequent amplification of MYC (8q24.21) in secondary AS and the rising incidence of PRAS and atypical vascular lesions (AVLs) have prompted interest in the diagnostic and prognostic utility of MYC in AS. METHODS: Retrospective series with ≥2 cases of cutaneous AS and describing the use of fluorescence in situ hybridization (FISH) for MYC amplification or immunohistochemistry (IHC) for MYC overexpression were included. RESULTS: Sixteen studies met inclusion criteria. Overall, 93% of cases evaluated by FISH and IHC were concordant. The sensitivity of FISH in primary AS was only 6.8%, and protein overexpression occurred without amplification in sun-damaged skin. FISH and IHC were over 78% sensitive in secondary AS but negative in over 98% of AVLs. MYC amplification and FLT4 coamplification were associated with shorter overall survival in secondary AS. CONCLUSION: FISH for MYC amplification and IHC for MYC overexpression are useful in distinguishing PRAS from AVLs and may also have prognostic value in secondary AS. In contrast, these methods have little diagnostic or prognostic value in primary AS and should not be used to distinguish primary AS from benign vascular neoplasms.

Screening of chronic radiation proctitis and colorectal cancer using periodic total colonoscopy after external beam radiation therapy for prostate cancer.

OBJECTIVE: To investigate the incidence of colorectal cancer and chronic radiation proctitis after prostate radiotherapy using periodic total colonoscopy screening. METHODS: From February 2013 to January 2018, 270 patients who underwent external beam radiation therapy for prostate cancer were advised to receive periodic total colonoscopy screening annually. We evaluated the incidence and characteristics of colorectal cancer and chronic radiation proctitis. RESULTS: First, second, third, fourth and fifth total colonoscopy were performed in 256 (95%), 151 (56%), 60 (22%), 23 (8.5%) and 7 (2.6%) patients at a median of 14, 31, 42, 54 and 72 months after radiotherapy, respectively. The prevalence proportion of colorectal cancer in the first colonoscopy since radiotherapy was 3.9%. Twelve (4.4%) patients were diagnosed with colorectal cancer, including four invasive cancers, during a follow-up period. Eight of these 12 patients had not experienced rectal bleeding. The median time to diagnosis of colorectal cancer was 21 months. Chronic radiation proctitis was observed in 136 (50%) patients, including 67 (25%) patients with symptomatic bleeding. CONCLUSIONS: The high detection rate of asymptomatic radiation proctitis suggests the utility of total colonoscopy to screen for early-stage colorectal cancer prior to or following radiotherapy for prostate cancer. Considering the longevity after localized prostate cancer treatment, the awareness of chronic radiation-induced proctitis and the risk of colorectal cancer masked by bleeding is needed in treatment decision -making.

Innumerable Meningiomas Arising in a Patient With Tuberous Sclerosis Complex Decades After Radiation Therapy.

Meningioma is the most common radiation-induced brain neoplasm, usually occurring after a latency of 20 - 35 years, with multiplicity in 10% of cases. Radiation-induced meningiomas (RIMs) have not previously been reported in patients with tuberous sclerosis complex (TSC), unlike their well-known occurrence in other familial tumor predisposition syndrome patients. We report a TSC patient who developed numerous intracranial meningiomas twenty five year after radiation therapy for subependymal giant cell astrocytoma (SEGA). Autopsy examination showed innumerable, coalescent, benign, meningothelial meningiomas, WHO grade 1, ranging in size from 0.2 cm to 3.3 cm. Autopsy also showed small residual SEGA, radiation-induced cerebral vasculopathy, and classic TSC features including several small subependymal nodules ("candle gutterings"), white matter radial heterotopia, facial angiofibromas, dental enamel pitting, one ash leaf spot, and multiple hepatic and renal angiomyolipomas. Next-generation sequencing analysis utilizing a 500+ gene cancer panel demonstrated chromosomal loss involving the majority of chromosome 22, including the NF2 gene locus, as well as a truncating nonsense mutation in TSC1 p. R509*. While TSC patients rarely require radiation therapy, this striking case suggests that patients with TSC should be monitored closely if cranial therapeutic radiation is administered.

MYC and NOTCH1-positive postradiation cutaneous angiosarcoma of the breast.

Postradiation cutaneous angiosarcoma of the breast is a rare, delayed complication of adjuvant radiation treatment for breast carcinoma and is associated with a worse prognosis than the original primary cancer. Recent studies have characterized the diagnostic utility of MYC and NOTCH1 receptor expression as markers for secondary radiation-associated angiosarcomas. Herein, we report an exophytic secondary breast angiosarcoma with MYC and NOTCH1 immunoreactivity. This case illustrates the utility of these markers for the identification of radiation-associated angiosarcoma with MYC and NOTCH1 expression, potential for targeted therapy and need to identify patients for further studies of the clinicopathologic and prognostic significance.

Atypical vascular lesions extending outside the radiation field: a diagnostic challenge.

Atypical vascular lesion (AVL) is an uncommon, benign vascular proliferation seen in previously irradiated skin, most commonly after radiotherapy for breast cancer. Atypical vascular lesion and angiosarcoma may share overlapping clinical and histopathologic features. We report the first case of AVL occurring outside the field of radiation. This patient's clinical course and histopathology was overall consistent with AVL, including two biopsies with focal MYC positivity. However, due to variations in the interpretation of her histopathology, the management plans devised by two centers involved in her care were widely discordant and she was treated with chemotherapy and extensive surgery for angiosarcoma. Great care must be taken to distinguish between these entities, as treatment for angiosarcoma may be associated with significant morbidity.

Misclassification of primary liver cancer in the Life Span Study of atomic bomb survivors.

Primary liver cancer is difficult to diagnose accurately at death, due to metastases from nearby organs and to concomitant diseases, such as chronic hepatitis and cirrhosis. Trends in diagnostic accuracy could affect radiation risk estimates for incident liver cancer by altering background rates or by impacting risk modification by sex and age. We quantified the potential impact of death-certificate inaccuracies on radiation risk estimates for liver cancer in the Life Span Study of atomic bomb survivors. True-positive and false-negative rates were obtained from a previous study that compared death-certificate causes of death with those based on pathological review, from 1958 to 1987. We assumed various scenarios for misclassification rates after 1987. We obtained estimated true positives and estimated false negatives by stratified sampling from binomial distributions with probabilities given by the true-positive and false-negative rates, respectively. Poisson regression methods were applied to highly stratified person-year tables of corrected case counts and accrued person years. During the study period (1958-2009), there were 1,885 cases of liver cancer, which included 383 death-certificate-only (DCO) cases; 1,283 cases with chronic liver disease as the underlying cause of death; and 150 DCO cases of pancreatic cancer among 105,444 study participants. Across the range of scenarios considered, radiation risk estimates based on corrected case counts were attenuated, on average, by 13-30%. Our results indicated that radiation risk estimates for liver cancer were potentially sensitive to death-certificate inaccuracies. Additional data are needed to inform misclassification rates in recent years.

MYC expression has limited utility in the distinction of undifferentiated radiation-associated sarcomas from sporadic sarcomas and sarcomatoid carcinoma.

AIMS: MYC is a proto-oncogene that is frequently dysregulated in various malignancies, through translocation or amplification. Radiation-associated angiosarcoma frequently shows MYC amplification, and immunohistochemical expression has been shown to be a reliable surrogate marker for amplification, but less is known about MYC expression in other sarcoma types, despite reports of MYC amplification in some undifferentiated/unclassified radiation-associated sarcomas (RASs). Distinguishing putative RAS from non-radiation-associated sarcoma or sarcomatoid carcinoma can be difficult. The aim of this study was to determine the prevalence and potential diagnostic utility of MYC in this context, by evaluating MYC expression in a cohort of RASs, non-radiation-associated sarcomas, and sarcomatoid carcinomas. METHODS AND RESULTS: Three hundred and eighty-five neoplasms were evaluated, including 81 RASs (18 angiosarcomas; 57 undifferentiated sarcomas; three leiomyosarcomas; and three malignant peripheral nerve sheath tumours), 267 non-radiation-associated sarcomas, and 37 sarcomatoid carcinomas. Immunohistochemistry was performed with a monoclonal anti-MYC antibody. Staining in tumour cells was scored on the basis of extent (focal, 1-4%; multifocal, 5-49%; and diffuse, ≥50%) and intensity (strong, moderate, and weak). One hundred percent of radiation-associated angiosarcomas expressed MYC diffusely. Expression was infrequent among other types of RAS (9.5%), and the frequency was similar to that in non-radiation-associated sarcomas (9.7%). MYC expression was more common in sarcomatoid carcinomas, occurring in 43%. The extent and intensity of staining were variable in all groups. CONCLUSION: MYC expression is infrequent among RASs other than angiosarcoma, and has a similar prevalence in sporadic sarcomas. Given the frequency of expression in sarcomatoid carcinomas, MYC expression outside the context of radiation-associated angiosarcoma is of limited diagnostic utility, and should be interpreted with caution after exclusion of sarcomatoid carcinoma where relevant.

Melanoma Genomics.

The incidence of cutaneous melanoma continues to increase in pale skinned peoples in Europe and elsewhere. Epidemiological studies identified genetically determined phenotypes such as pale skin, freckles and red hair, and sunburn as risk factors for this cancer. The development of many melanocytic naevi is also genetically determined and a strong melanoma risk phenotype. Not surprisingly then, genome wide association studies have identified pigmentation genes as common risk genes, and to a lesser extent, genes associated with melanocytic naevi. More unexpectedly, genes associated with telomere length have also been identified as risk genes. Higher risk susceptibility genes have been identified, particularly CDKN2A as the most common cause, and very rarely genes such as CDK4, POT1, TERT and other genes in coding for proteins in the shelterin complex are found to be mutated. Familial melanoma genes are associated with an increased number of melanocytic naevi but not invariably and the atypical naevus phenotype is therefore an imperfect marker of gene carrier status. At a somatic level, the most common driver mutation is BRAF, second most common NRAS, third NF1 and increasing numbers of additional rarer mutations are being identified such as in TP53. It is of note that the BRAF and NRAS mutations are not C>T accepted as characteristic of ultraviolet light induced mutations.

Melanoma Epidemiology and Sun Exposure.

The worldwide incidence of melanoma has increased rapidly over the last 50 years. Melanoma is the most common cancer found in the young adult population, and its incidence is very high among geriatric populations. The incidence of melanoma varies by sex, and this factor is also associated with differences in the anatomical site melanoma. Adolescent and young adult women have a higher incidence than men. This may be, in part, due to the greater use of sunbeds, as well as intentional sun exposure among girls and, in general, risky behaviours in seeking to suntan, due to socially-determined aesthetic needs. Indeed, the World Health Organization declared that there is sufficient evidence to classify exposure to ultraviolet radiation (sunbed use and sun exposure) as carcinogenic to humans. Although pigmentation characteristics, such as skin colour, hair and eye colour, freckles and number of common and atypical naevi, do influence susceptibility to melanoma, recommendations regarding prevention should be directed to the entire population and should include avoiding sunbed, covering sun-exposed skin, wearing a hat and sunglasses. Sunscreen use should not be used to prolong intentional sun exposure. Primary prevention should be focused mainly on young adult women, while secondary prevention should be focused mainly on elderly men. In fact, after the age of 40 years, incidence rates reverse, and the incidence of melanoma among men is greater than among women. This is probably due to the fact that men are less likely than women to examine their own skin or present to a dermatologist for skin examination.

Update: Solar UV Radiation, Vitamin D, and Skin Cancer Surveillance in Organ Transplant Recipients (OTRs).

Although great progress has been achieved during the last decades, the clinical management of organ transplant recipients (OTRs) remains a challenge. OTRs need in general lifelong immunosuppressive therapy that is associated with an increased risk to develop skin cancer and with an unfavorable clinical outcome of these malignancies. Skin cancer prevention measures, including regular full-body examinations, are therefore necessary in OTRs to detect and treat suspicious lesions at an early stage. The frequency of aftercare depends on the individual risk factors of the patient. Patients should apply consistent sun protection with sunscreens and clothing, as well as a monthly self-examination. On the other hand, the need of UVR avoidance increases the risk of vitamin D deficiency, which itself is associated with an increased risk for many diseases, including malignancies. OTRs should therefore be monitored for 25(OH)D status and/or should take vitamin D supplements. It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist, is needed to ensure the best care for the OTRs.

Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study.

BACKGROUND: The risk of subsequent primary cancers in patients with prostate cancer after treatment with photon radiotherapy is small in absolute numbers, but it is higher than that after surgical treatment. Carbon ion radiotherapy has a theoretically lower risk of inducing secondary malignancies than photon radiotherapy, but this risk has not been investigated in practice because of the low number of facilities offering such therapy worldwide and the limited data on long-term follow-up because the therapy has only been available since 1994. We aimed to analyse the risk of subsequent primary cancers after treatment with carbon ion radiotherapy in patients with localised prostate cancer and to compare it with that after photon radiotherapy or surgery in this setting. METHODS: In this retrospective cohort study, we reviewed records of patients who received carbon ion radiotherapy for prostate cancer between June 27, 1995, and July 10, 2012, at the National Institute of Radiological Sciences (NIRS) in Japan. We also retrieved the records of patients diagnosed and treated for prostate cancer between Jan 1, 1994, and Dec 31, 2012, from the Osaka Cancer Registry. Eligible patients had histologically confirmed localised prostate cancer and a minimum follow-up of at least 3 months; no age restrictions were applied. We excluded patients with metastasis, node-positive disease, or locally invasive (T4 stage) prostate cancer, those with previous or synchronous malignancies, and those who received previous radiotherapy or chemotherapy. We did a multivariable analysis to estimate predictors of subsequent cancers after carbon ion radiotherapy treatment. We also used propensity score inverse probability weighting to retrospectively compare the incidence of subsequent cancers in patients with localised prostate cancer treated with carbon beams, photon radiotherapy, or surgery. FINDINGS: Of 1580 patients who received carbon radiotherapy for prostate cancer at the NIRS, 1455 (92%) patients met the eligibility criteria. Of 38 594 patients with prostate cancer identified in the Osaka registry, 1983 (5%) patients treated with photon radiotherapy and 5948 (15%) treated with surgery were included. Median follow-up durations were 7·9 years (IQR 5·9-10·0) for patients who received carbon ion radiotherapy (after limiting the database to 10-year maximum follow-up), 5·7 years (4·5-6·4) for patients who received photon radiotherapy, and 6·0 years (5·0-8·6) for those who received surgery. 234 subsequent primary cancers were diagnosed in the carbon ion radiotherapy cohort; some patients developed several tumours. On multivariable analysis, age (p=0·0021 for 71-75 years vs ≤60 years; p=0·012 for >75 years vs ≤60 years) and smoking (p=0·0005) were associated with a higher risk of subsequent primary cancers in patients treated with carbon ion radiotherapy. In the propensity score-weighted analyses, carbon ion radiotherapy was associated with a lower risk of subsequent primary cancers than photon radiotherapy (hazard ratio [HR] 0·81 [95% CI 0·66-0·99]; p=0·038) or surgery (HR 0·80 [0·68-0·95]; p=0·0088), whereas photon radiotherapy was associated with a higher risk of subsequent primary cancers than surgery (HR 1·18 [1·02-1·36]; p=0·029). INTERPRETATION: Our analysis suggests that patients with localised prostate cancer treated with carbon ion radiotherapy appear to have a lower risk of subsequent primary cancers than those treated with photon radiotherapy. Although prospective evaluation with longer follow-up is warranted to support these results, our data supports a wider adoption of carbon ion radiotherapy for patients with expected long-term overall survival or those with poor outcomes after receiving conventional treatments. FUNDING: Research Project for Heavy Ions at the National Institute of Radiological Sciences (Japan).