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Introduction: High-grade gliomas are central nervous system tumors conventionally treated with surgery followed by adjuvant chemoradiotherapy. Secondary cancer due to radiation therapy is a rare yet established phenomenon that typically occurs years after radiation therapy. Case Presentation: In this case, we discuss an early presentation of a second cancer adjacent to the radiation field. This case report is of a 52-year-old male who developed a new scalp sarcoma at the site of primary surgery 8 months after radiation therapy. Genetic testing revealed a heterozygous missense variant in the NF1 gene, a variant of uncertain significance. The report highlights that this case does not conform to the expected criteria for postradiation sarcoma in terms of timing. Conclusion: Secondary cancers may arise earlier than expected, even in phenotypically normal patients, as they may have unmanifested variants of relevant mutations. The question of pre-radiotherapy screening for radiosensitivity syndromes and diseases requires further study, as current data are limited and do not provide enough insight into the significance of different genetic variants.

Background: Aplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited. Methods: We retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition. Results: Nine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Conclusion: This study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7's prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression. [ABSTRACT FROM AUTHOR]

Introduction: High-grade gliomas are central nervous system tumors conventionally treated with surgery followed by adjuvant chemoradiotherapy. Secondary cancer due to radiation therapy is a rare yet established phenomenon that typically occurs years after radiation therapy. Case Presentation: In this case, we discuss an early presentation of a second cancer adjacent to the radiation field. This case report is of a 52-year-old male who developed a new scalp sarcoma at the site of primary surgery 8 months after radiation therapy. Genetic testing revealed a heterozygous missense variant in the NF1 gene, a variant of uncertain significance. The report highlights that this case does not conform to the expected criteria for postradiation sarcoma in terms of timing. Conclusion: Secondary cancers may arise earlier than expected, even in phenotypically normal patients, as they may have unmanifested variants of relevant mutations. The question of pre-radiotherapy screening for radiosensitivity syndromes and diseases requires further study, as current data are limited and do not provide enough insight into the significance of different genetic variants. [ABSTRACT FROM AUTHOR]

Abstract Objective The clinical characteristics and survival of patients with myeloproliferative neoplasms (MPNs) with secondary cancer were analyzed to explore the possible risk factors for secondary cancer in MPN patients. Methods The clinical characteristics of 1060 Chinese patients with MPN were retrospectively analyzed. The Kaplan–Meier method was used to analyze the survival. The Cox multivariate regression model was used to analyze the risk factors for developing secondary cancer in patients with MPNs. Results The 1060 patients with MPN had a median follow‐up of 10 years (range 1–50) and a median age of 55 years (range 21–86), and 497 (45.2%) were male. The proportion of PV, ET, and PMF was 52.2%, 33.5%, and 14.3%, respectively. About 28.1% (298/1060) of 1060 MPN patients died. The median survival times of the PV, ET, and PMF groups were 20, 24, and 12 years, respectively (p

Background: Childhood cancers affect 2,000-2,500 individuals per year in Japan, with onset at infancy. In Japan, there are ~50,000 childhood cancer survivors, and following recovery, the mother supports the child at home. Aim: To elucidate how mothers confront problems following the discharge of childhood cancer survivors and the provision of guidance to the child regarding self-care. Methodology: After creating an interview guide coinciding with the study objectives, semi-structured interviews of five mothers of childhood cancer survivors were conducted. The data obtained was analyzed using the modified grounded theory approach. Results: The challenges faced by mothers of childhood cancer survivors who underwent surgery as children and the self-care guidance process comprised 5 core categories and nine categories from 34 concepts. The core categories included "formation of beliefs to confront the disease," "promotion of understanding suitable to the child's age at onset," "individual actions against the lack of information," "preparation of the environment by oneself when the child needs to be monitored," and "reflection and acknowledgment of the process to date." Conclusions: The mothers of childhood cancer survivors with onset at infancy preferred for the child to understand their disease; however, the mothers experienced difficulty in explaining the disease owing to a lack of knowledge. To enhance their knowledge to facilitate the child's self-care, mothers joined patient groups to gather information. Furthermore, following discharge, it was difficult for parents and their children to establish relationships with medical staff and no avenue was available for consultation in case of any concerns. [ABSTRACT FROM AUTHOR]

Introduction Ewing sarcoma family tumor is a malignant tumor that is primarily of bone origin; it rarely occurs in the kidney. Case presentation A 22‐year‐old woman presented with hematuria. Computed tomography revealed a 6 × 6‐cm mass in the lower pole of the right kidney with invasion into the right renal vein. A right laparoscopic radical nephrectomy was performed. The tumor was completely encapsulated. Based on the small‐round‐cell histology, diffusely CD99‐positive tumor cells, and EWS (ex7)–FLi1 (ex6) fusion gene break point transcript, we diagnosed Ewing sarcoma/primitive neuroectodermal tumor of the kidney. After surgery, eight cycles of adjuvant chemotherapy including vincristine, doxorubicin (Adriamycin®), cyclophosphamide, ifosfamide, and etoposide were given. No evidence of recurrence has been observed 13 months from diagnosis. Conclusion This was a rare Ewing sarcoma family tumor in the kidney of a young female with no remarkable family medical history.

Objective: The clinical characteristics and survival of patients with myeloproliferative neoplasms (MPNs) with secondary cancer were analyzed to explore the possible risk factors for secondary cancer in MPN patients. Methods: The clinical characteristics of 1060 Chinese patients with MPN were retrospectively analyzed. The Kaplan–Meier method was used to analyze the survival. The Cox multivariate regression model was used to analyze the risk factors for developing secondary cancer in patients with MPNs. Results: The 1060 patients with MPN had a median follow‐up of 10 years (range 1–50) and a median age of 55 years (range 21–86), and 497 (45.2%) were male. The proportion of PV, ET, and PMF was 52.2%, 33.5%, and 14.3%, respectively. About 28.1% (298/1060) of 1060 MPN patients died. The median survival times of the PV, ET, and PMF groups were 20, 24, and 12 years, respectively (p < 0.0001). In age‐ and sex‐matched healthy Chinese patients, the standardized incidence ratio (SIR) value of developing secondary cancer in MPN patients was 6.41 (95% CI: 4.90–9.48). The median survival time was 14 years in the MPN with secondary cancer group. The Cox multivariate analysis showed that age ≥ 65 years (p < 0.0001, HR = 5.027, 95% CI [2.823, 8.952]), MF‐1 (p = 0.001, HR = 2.887, 95% CI [1.503, 5.545]) were risk factors for developing secondary cancer. Conclusions: The survival of MPN patients with secondary cancer was significantly worse than that of patients without secondary cancer. Compared with normal subjects, MPN patients had a 6.41‐fold increased risk of developing secondary cancer, and age ≥ 65 years and MF‐1 were risk factors for developing secondary cancer in MPN patients. [ABSTRACT FROM AUTHOR]

Endocrine therapy is the mainstay treatment for hormone receptor-positive ductal carcinoma in situ. The aim of this study was to examine the long-term secondary malignancy risk of tamoxifen therapy. The data of patients diagnosed with breast cancer between January 2007 and December 2015 were retrieved from the database of the Health Insurance Review and Assessment Service of South Korea. The International Classification of Diseases, 10th revision, was used to track all-site cancers. Age at the time of surgery, chronic disease status, and type of surgery were considered covariates in the propensity score matching analysis. The median follow-up duration was 89 months. Forty-one patients in the tamoxifen group and nine in the control group developed endometrial cancer. The Cox regression hazard ratio model showed that tamoxifen therapy was the only significant predictor of the development of endometrial cancer (hazard ratio, 2.791; 95% confidence interval, 1.355–5.747; p = 0.0054). No other type of cancer was associated with long-term tamoxifen use. In consonance with the established knowledge, the real-world data in this study demonstrated that tamoxifen therapy is related to an increased incidence of endometrial cancer. [ABSTRACT FROM AUTHOR]

We investigated the risk of secondary cancers in rectum and bladder for prostate cancer radiotherapy using a feasibility assessment tool. We calculated the risk of secondary cancer by generating a dose-volume histogram based on an ideal dose falloff function (f-value). This study found a smaller f-value was associated with a lower secondary cancer risk in the rectum but a higher risk in the bladder. The study suggests setting the f-value at 0-0.1 as the optimization goal for the rectum and 0.4 for the bladder is reasonable and feasible for reducing the risk of secondary cancer and other adverse events.

Abstract Aim Esophagogastroduodenoscopy (EGD) may contribute to early detection of secondary cancer in the upper gastrointestinal tract although the clinical relevance of follow‐up after gastrectomy remains unclear. This study aimed to elucidate the effectiveness of follow‐up EGD by investigating the incidence of secondary cancer in any part of the upper gastrointestinal tract. Methods Data from 1438 patients who underwent curative partial gastrectomy for primary gastric cancer between 2008 and 2014 and follow‐up EGD at least once during a 5‐year follow‐up period were retrospectively reviewed. Incidence rates of remnant gastric cancer, laryngeal cancer, and esophageal cancer detected after follow‐up EGD were determined, and risk factors for secondary cancers were examined. The characteristics of clinicopathological diagnoses of secondary cancers were reviewed and compared according to the frequency of follow‐up EGD. Results The average annual frequency of EGD was 0.7, while the 5‐year cumulative incidence rates of remnant gastric cancer and secondary laryngeal and esophageal cancers were 2.9% and 1.3%, respectively. Risk factors for remnant gastric cancer included heavy smoking, proximal gastrectomy, and tumor size ≥ 30 mm. All secondary cancers were resectable upon diagnosis, with endoscopically resectable cancer accounting for 81.0% of cases. Our results found a significantly higher proportion of endoscopically resectable cancers during regular follow‐up than during infrequent follow‐up. Conclusions Follow‐up EGD can be a useful modality for detecting secondary upper gastrointestinal tract cancer, likely leading to curative treatment for secondary cancer. Focusing on patients presenting with risk factors may increase the value of follow‐up EGD after gastrectomy.

Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa.

Considering that cancer survival rates have been growing and that nearly two-thirds of those survivors were exposed to clinical radiation during its treatment, the study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. To correctly assess this risk, knowing the dose to out-of-field organs is essential. As it has been reported, commercial treatment planning systems do not accurately calculate the dose far away from the border of the field; analytical dose estimation models may help this purpose. In this work, the development and validation of a new three-dimensional (3D) analytical model to assess the photon peripheral dose during radiotherapy is presented. It needs only two treatment-specific input parameter values, plus information about the linac-specific leakage, when available. It is easy to use and generates 3D whole-body dose distributions and, particularly, the dose to out-of-field organs (as dose–volume histograms) outside the 5% isodose for any isocentric treatment using coplanar beams [including intensity modulated radiotherapy and volumetric modulated arc therapy (VMAT)]. The model was configured with the corresponding Monte Carlo simulation of the peripheral absorbed dose for a 6 MV abdomen treatment on the International Comission on Radiological Protection (ICRP) 110 computational phantom. It was then validated with experimental measurements using thermoluminescent dosimeters in the male ATOM anthropomorphic phantom irradiated with a VMAT treatment for prostate cancer. Additionally, its performance was challenged by applying it to a lung radiotherapy treatment very different from the one used for training. The model agreed well with measurements and simulated dose values. A graphical user interface was developed as a first step to making this work more approachable to a daily clinical application.

Aim: Esophagogastroduodenoscopy (EGD) may contribute to early detection of secondary cancer in the upper gastrointestinal tract although the clinical relevance of follow‐up after gastrectomy remains unclear. This study aimed to elucidate the effectiveness of follow‐up EGD by investigating the incidence of secondary cancer in any part of the upper gastrointestinal tract. Methods: Data from 1438 patients who underwent curative partial gastrectomy for primary gastric cancer between 2008 and 2014 and follow‐up EGD at least once during a 5‐year follow‐up period were retrospectively reviewed. Incidence rates of remnant gastric cancer, laryngeal cancer, and esophageal cancer detected after follow‐up EGD were determined, and risk factors for secondary cancers were examined. The characteristics of clinicopathological diagnoses of secondary cancers were reviewed and compared according to the frequency of follow‐up EGD. Results: The average annual frequency of EGD was 0.7, while the 5‐year cumulative incidence rates of remnant gastric cancer and secondary laryngeal and esophageal cancers were 2.9% and 1.3%, respectively. Risk factors for remnant gastric cancer included heavy smoking, proximal gastrectomy, and tumor size ≥ 30 mm. All secondary cancers were resectable upon diagnosis, with endoscopically resectable cancer accounting for 81.0% of cases. Our results found a significantly higher proportion of endoscopically resectable cancers during regular follow‐up than during infrequent follow‐up. Conclusions: Follow‐up EGD can be a useful modality for detecting secondary upper gastrointestinal tract cancer, likely leading to curative treatment for secondary cancer. Focusing on patients presenting with risk factors may increase the value of follow‐up EGD after gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. Case presentation: A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. Conclusion: This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.

Endocrine therapy is the mainstay treatment for hormone receptor-positive ductal carcinoma in situ. The aim of this study was to examine the long-term secondary malignancy risk of tamoxifen therapy. The data of patients diagnosed with breast cancer between January 2007 and December 2015 were retrieved from the database of the Health Insurance Review and Assessment Service of South Korea. The International Classification of Diseases, 10th revision, was used to track all-site cancers. Age at the time of surgery, chronic disease status, and type of surgery were considered covariates in the propensity score matching analysis. The median follow-up duration was 89 months. Forty-one patients in the tamoxifen group and nine in the control group developed endometrial cancer. The Cox regression hazard ratio model showed that tamoxifen therapy was the only significant predictor of the development of endometrial cancer (hazard ratio, 2.791; 95% confidence interval, 1.355–5.747; p = 0.0054). No other type of cancer was associated with long-term tamoxifen use. In consonance with the established knowledge, the real-world data in this study demonstrated that tamoxifen therapy is related to an increased incidence of endometrial cancer.

Prostate cancer is the most common and second leading cause of death among men in the world. Nowadays, radiotherapy has been known as one of the most affecting methods for prostate cancer treatment. Nevertheless, radiotherapy is accompanied by the concern of developing secondary cancers by the scattered radiation to the neighbor organs at risk. Several studies have shown that secondary cancers after the radiotherapy of prostate cancer treatment, occur in tissues such as the bladder and rectum which have been exposed to direct or indirect radiations. Therefore, this review study aimed to evaluate the influencing factors for developing secondary cancers after the radiotherapy of prostate cancer. To access the previously validated published studies, Persian and English keywords such as prostate cancer, secondary cancers, radiotherapy and organs at risk have been searched in ISID, Google Scholar, Science Direct, PubMed, and World Health Organization, between 1997 and 2021. Totally 246 pieces of literature have been selected which finally, by ignoring the similar and overlapping studies, only 40 studies were reviewed. In the present study, the most affecting factors for developing secondary malignancies including the anatomical status changes, dose variations, smoking and the impact of the various treatment techniques, have been studied. The results of the reviewed studies showed a reduction of secondary cancer risks with performing the modern modalities such as proton therapy to treat prostate cancer. Moreover, organ movements and anatomical status changes which vary from one patient to others, have been reported to make a significant difference in the relative risk of secondary cancers. It has been shown that smoking may increase the risk of secondary cancers after the radiotherapy of prostate cancer, so radiotherapy and smoking may cause genetic mutations. Despite the advantages of radiotherapy for prostate cancer treatment, developing secondary cancers after the radiotherapy should not be ignored. Assessments of the affecting factors for secondary cancers after the radiotherapy of prostate cancer require social and comprehensive studies which can result in an accurate modality with fewer side effects. [ABSTRACT FROM AUTHOR]

Thymoma is a very rare tumor with a rate of 1.7 per million. Thymoma often occurs between the ages of 35-70. Thymoma is frequently located in the anterior mediastinum. Patients with thymoma often do not cause symptoms clinically. Depending on the localization of the tumor, pain may present with cough, hoarseness, shortness of breath, superior vena cava syndrome and weight loss. The coexistence of nasopharyngeal, breast, colon and hepatocellular cancer can be seen in patients with thymomas. In this article, we present our case with thymoma and colon cancer association with the literature.

Background ‒ Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa. Methods ‒ The differentially expressed genes (DEGs) between preradiation and postradiation BCa samples in the GSE65505 dataset were obtained. The pathways related to the radiation-associated DEGs in the protein–protein interaction (PPI) network modules were identified. miRNAs targeted to the key genes in the PPI network were identified, and their association with BCa prognosis was analyzed. Results ‒ A total of 136 radiation-associated DEGs preradiation and postradiation BCa samples were screened out. The PPI network consisted of a significant module that consisted of 21 upregulated DEGs that were associated with “hsa04512: ECM–receptor interaction,” “hsa04151: PI3K-Akt signaling pathway,” and “hsa04115: p53 signaling pathway.” Sixteen DEGs, including three collagen genes collagen type I alpha 1 chain (COL1A1), COL3A1, and COL1A2, were enriched in 17 radiation-associated pathways. The three genes were upregulated in BCa tissues compared with controls and were also elevated by radiation. They were targeted by hsa-miR-29a/c, and the expression levels of hsa-miR-29a/c were associated with a poor prognosis of BCa. Conclusions ‒ The upregulation of COL1A1, COL3A1, and COL1A2 might be genetic risk factors for radiationassociated secondary diseases in BCa. [ABSTRACT FROM AUTHOR]

Hodgkin lymphoma survivors who received mantle radiation are at risk of developing secondary malignant neoplasms. There is no established recommended screening guideline for this population. We discuss the case of a patient with a history of Hodgkin lymphoma status post-mantle field radiation, thyroid cancer status post-thyroidectomy, and now breast cancer following mantle radiation. The risk of adverse effects from mantle field radiation is well documented and includes secondary cancers of the thyroid, breast, lung, and cardiovascular disease. Advances in technology have led to an international paradigm shift in the management of Hodgkin lymphoma to reduce the diameter and dose of radiation based on the patient's anatomy. However, there is no consensus regarding the optimal frequency or modality of breast cancer screening in patients with Hodgkin lymphoma status post-mantle radiation who are now in remission. We discuss screening methods for this population, which has a high risk of developing breast cancer, and emphasize the need for personalized medicine., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Sovah Health Martinsville IRB issued approval IRB-IORG# 0003200FWA-VA043. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mansour et al.)

Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa). Material and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses. Results: We identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa. Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Secondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques. Patients and Methods: The SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature. Results: Out of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p<0.001). More advanced stages did not have significantly increased risk. In 2019, 104,743 early-stage breast patients received radiotherapy, and an estimated 3,413 will develop SLC (3.25%) leading to an excess of 2,900 deaths (2.77%). VMAT would reduce this mortality by 9.9%, hypofractionation 26 Gy in five fractions by 38.8%, a prone technique by 70.3%, 3D-CRT APBI by 43.3%, HDR brachytherapy by 71.1%, LDR by 80.7%, and robotic 4π APBI by 85.2%. Conclusions: SLC after breast RT remains a clinically significant issue for early-stage breast cancers. This mortality could be significantly reduced using a prone technique or APBI. [ABSTRACT FROM AUTHOR]

BackgroundThis study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).Material and MethodsWithin the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses.ResultsWe identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.ConclusionPatients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.

PurposeSecondary lung cancer (SLC) can offset the benefit of adjuvant breast radiotherapy (RT), and risks compound sharply after 25 to 30 years. We hypothesized that SLC risk is mainly an issue for early-stage breast cancer, and that lives could be saved using different RT techniques.Patients and MethodsThe SEER database was used to extract breast patient age, stage survival, and radiotherapy utilization over time and per stage and to assess the factors associated with increased SLC risk with a multivariable competing risk Cox model. The number of SLC was calculated using the BEIR model modified with patient survival, age, and use of RT from the SEER database. Stage distribution and number of new breast cancer cases were obtained from the NAACCR. Mean lung dose for various irradiation techniques was obtained from measurement or literature.ResultsOut of the 765,697 non-metastatic breast cancers in the SEER database from 1988 to 2012, 49.8% received RT. RT significantly increased the SLC risk for longer follow-up (HR=1.58), early stage including DCIS, stage I and IIA (HR = 1.11), and younger age (HR=1.061) (all p

Cyclophosphamide is a nitrogen mustard class of drugs that are often used in cancer chemotherapy. However, the use of Cyclophosphamide in high doses over a long period has been shown to increase the risk of developing secondary cancer. This can be indicated by the formation of mutagenic DNA adducts, such as O6-Methylguanine. Therefore, this adduct can be used as a biomarker for secondary cancer in patients receiving Cyclophosphamide. Bio sampling was carried out by using the Dried Blood Spot (DBS) method, followed by DNA extraction by using QIAamp DNA mini kit, and acid hydrolysis to obtain O6-Methylguanine. Analysis of O6-Methylguanine was performed by using the UPLC-MS/MS instrument with the conditions developed by Vianney, Harahap, & Suryadi (2021). Partial validation was carried out before the analysis. The results obtained from the calibration curve, accuracy, and precision validation test met the FDA requirements. The analysis method was then implemented in 16 breast cancer patients who received the Cyclophosphamide regimen. The O6-Methylguanine was successfully detected and quantified in all of the samples in the range of 0.55–6.66 ng/mL. It shows that the O6-Methylguanine accumulation in cancer patients receiving Cyclophosphamide is very likely to occur and the analysis method proposed by Vianney, Harahap, & Suryadi (2021) is potential to be used for Therapeutic Drug Monitoring in this group of patients.

Purpose: This study investigated radioactive iodine treatment (RAIT) patterns and the secondary cancer incidence among children and young adults receiving RAIT after thyroidectomy for thyroid cancer.Methods: This population-based cohort study used the Health Insurance Review and Assessment database of South Korea to identify a total of 18 617 children and young adults (0-29 years) who underwent thyroidectomy for thyroid cancer between 2008 and 2018. We recorded age at surgery, sex, the interval from surgery to RAIT, the doses of RAI, the number of RAIT sessions, and secondary cancer incidence.Results: A total of 9548 (51.3%) children and young adults underwent 1 or more RAIT sessions. The initial dose of RAIT was 4.35 ± 2.19 GBq. The overall RAIT frequency fell from 60.9% to 38.5%, and the frequency of high-dose RAIT (>3.7 GBq) fell from 64.2% to 36.5% during the observational period. A total of 124 cases of secondary cancer developed during 120 474 person-years of follow-up; 43 (0.5%) in the surgery cohort and 81 (0.8%) in the RAIT cohort. Thus, the RAIT cohort was at an increased risk of secondary cancer (adjusted hazard ratio 1.52 [95% confidence interval 1.03-2.24], P = 0.035).Conclusion: The proportion of children and young adults receiving RAIT, and the RAI dose, fell significantly over the observational period. RAIT was associated with secondary cancers. This is of major concern in the context of child and young adult thyroid cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to estimate the impact of the addition of internal mammary chain (IMC) irradiation in node-positive left-sided breast cancer (BC) patients undergoing regional nodal irradiation (RNI) and comparatively evaluate excess relative and absolute risks of radiation-induced lung cancer/BC and ischaemic heart disease for intensity-modulated radiotherapy (IMRT) versus 3D conformal radiotherapy (3D-CRT). Methods: Four treatment plans were created (3D-CRT and IMRT –/+ IMC) for each of the 10 evaluated patients, and estimates of excess relative risk (ERR) and 10-year excess absolute risk (EAR) were calculated for radiation-induced lung cancer/BC and coronary events using linear, linear-exponential and plateau models. Results: The addition of IMC irradiation to RNI significantly increased the dose exposure of the heart, lung and contralateral breast using both techniques, increasing ERR for secondary lung cancer (58 vs. 44%, p = 0.002), contralateral BC (49 vs. 31%, p = 0.002) and ischaemic heart disease (41 vs. 27%, p = 0.002, IMRT plans). IMRT significantly reduced the mean cardiac dose and mean lung dose as compared to 3D-CRT, decreasing ERR for major coronary events (64% 3D-CRT vs. 41% IMRT, p = 0.002) and ERR for secondary lung cancer (75 vs. 58%, p = 0.004) in IMC irradiation, without a significant impact on secondary contralateral BC risks. Conclusion: Although IMC irradiation has been shown to increase survival rates in node-positive BC patients, it increased dose exposure of organs at risk in left-sided BC, resulting in significantly increased risks for secondary lung cancer/contralateral BC and ischaemic heart disease. In this setting, the adoption of IMRT seems advantageous when compared to 3D-CRT. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic body radiotherapy (SBRT) currently adopts non-discriminative prescription regimen. This study attempts to investigate an individualized fraction regimen (IFR) method for SBRT patients with non-small cell lung cancer (NSCLC) based on Uncomplicated and Cancer-free Control Probability (UCFCP). Methods: Twenty patients with NSCLC were retrospectively prescribed with 40 regimens, ranging from 8Gy×5f to 12Gy×5f in step of 0.1 Gy. Taking into consideration of the age and the BMI index of each patient as well, the tumor control probability (TCP), the normal tissue complication probability (NTCP) of the total lung, chest wall and rib, and the secondary cancer probability (SCP) of the total lung were calculated for each plan of the patients. For the 40 regimens, the UCFCP was calculated and the maximum value of UCFCP was the IFR of the specified patient. Besides, IFR of UCP approach which only took account of the TCP and NTCP was also derived and to be compared with the IFR based on the UCFCP method. Results: For all the patients, the UCFCP value showed a bell-shaped trend with the change of prescription dose. Among the 20 patients, the IFRs of 16 patients were different from the original fixed regimen. Of the 16 patients, the IFR of 5 patients exhibited slight changes between UCP and UCFCP methods. Conclusion: The method based on the maximum value of UCFCP function may be helpful to provide IFR for specific SBRT patients with NSCLC, differentiating the patient specific characteristics such as anatomical structures and locations. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy plays an important role in the management of cancer. Although the improved technologies increase therapeutic index, different delivery techniques deliver different dose pattern to the healthy tissue within and outside treatment volume. Objective: The objective of this study was to evaluate the low, intermediate, and high dose to healthy tissue within and outside the treatment volume and to find the relation between tumor volume and various doses received healthy tissue volume. Materials and Methods: A total of 150 patients were included. For all patients, planning computed tomography images were acquired. Tumors, critical structures, and healthy tissue volumes at different regions were delineated. Two sets of plans, one with volumetric-modulated arc therapy and another with intensity-modulated radiation therapy (IMRT) were created, optimized for 6 MV photons and dose was calculated. Dosimetry results for tumor, organs at risks (OARs), and healthy tissue from both the techniques were evaluated and compared. Results: Tumor coverage and dose to OARs was significantly better with volumetric-modulated arc therapy (VMAT). Volume of healthy tissue received high-dose within the treatment volume as well as volume of healthy tissue received low and intermediate-dose out of treatment volume were significantly (P < 0.002) lesser with VMAT. Besides, the results showed that as the tumor volume increased, the various dose received healthy tissue volume also increased. Conclusions: VMAT plan can reduce the risk of secondary malignancy while treating different sites of cancer. VMAT is the most appropriate technique than IMRT, especially in the treatment of large tumor volume. Special attention has to be given, especially while treating women and children.

Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon.

Background: Aplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited., Methods: We retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition., Results: Nine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia., Conclusion: This study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7's prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression., Competing Interests: Authors S-TL and JRC were employed by the company Dxome Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Choi, Lee, Choi, Lyu, Shin and Cheong.)

This work concerns neutron doses associated with the use of a Siemens Primus M5497 electron accelerator, which is operated in the photon mode at 15 MV. The conditions offer a situation within which a fraction of the bremsstrahlung emission energies exceed the photoneutron threshold. For different field sizes, an investigation has been made of neutron dose equivalent values at various measurement locations, including: (i) At the treatment table, at a source-surface distance of 100 cm; (ii) at the level of the floor directly adjacent to the treatment table; and (iii) in the control room and patient waiting area. The evaluated neutron dose equivalent was found to range from 0.0001 to 8.6 mSv/h, notably with the greatest value at the level of the floor directly adjacent to the treatment couch (8.6 mSv/h) exceeding the greatest value on the treatment table (5.5 mSv/h). Low values ranging from unobservable to between 0.0001 to 0.0002 mSv/h neutron dose were recorded around the control room and patient waiting area. For measurements on the floor, the study showed the dose equivalent to be greatest with the jaws closed. These data, most particularly concerning neutron distribution within the treatment room, are of great importance in making steps towards improving patient safety via the provision of protective measures.

Li-Fraumeni syndrome (LFS) is a genetic disease that is hypersensitive to radiotherapy. Proton therapy (PT) was strongly recommended for pediatric and radiation-sensitive tumors. However, there is little information on PT for LFS. The patient was a 7-year-old girl with LFS who was diagnosed with radiation-induced right shoulder blade osteosarcoma and left chest wall malignant fibrous histiocytoma. Both tumors were in the area that had previously been irradiated (36–45 Gy by photon radiotherapy). Sixty-six GyE in 30 fractions was planned for both tumors. We set the clinical target to the minimum gross tumor volume. To comprehensively assess any adverse events, PT was conducted under hospital administration. Cisplatin was used as simultaneous combination chemotherapy. Although administration of granulocyte-colony stimulating factor was necessary for myelosuppression by chemotherapy, PT was completed without interruption. Acute radiation toxicity was observed as Grade 1 dermatitis. The dermatitis became exacerbated 2 weeks after PT but subsequently improved with conservation treatment alone. Twenty-three months after PT, magnetic resonance imaging showed an increase in the tumor on the right shoulder. A histological examination was not conducted as the family declined, but secondary cancer was suggested rather than recurrent osteosarcoma, as the tumor developed mainly from the soft tissue. Additional surgical treatment and radiotherapy were not indicated, and the patient died of tumor progression and sepsis caused by myelosuppression 27 months after undergoing PT. Up to 23 months after PT, there were no signs of Grade 2 or more late toxicities. This represents the first reported case of PT for a patient with LF to treat radiation-induced secondary cancer. [ABSTRACT FROM AUTHOR]

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Background: Radiotherapy plays an important role in the management of cancer. Although the improved technologies increase therapeutic index, different delivery techniques deliver different dose pattern to the healthy tissue within and outside treatment volume. Objective: The objective of this study was to evaluate the low, intermediate, and high dose to healthy tissue within and outside the treatment volume and to find the relation between tumor volume and various doses received healthy tissue volume. Materials and Methods: A total of 150 patients were included. For all patients, planning computed tomography images were acquired. Tumors, critical structures, and healthy tissue volumes at different regions were delineated. Two sets of plans, one with volumetric-modulated arc therapy and another with intensity-modulated radiation therapy (IMRT) were created, optimized for 6 MV photons and dose was calculated. Dosimetry results for tumor, organs at risks (OARs), and healthy tissue from both the techniques were evaluated and compared. Results: Tumor coverage and dose to OARs was significantly better with volumetric-modulated arc therapy (VMAT). Volume of healthy tissue received high-dose within the treatment volume as well as volume of healthy tissue received low and intermediate-dose out of treatment volume were significantly (P < 0.002) lesser with VMAT. Besides, the results showed that as the tumor volume increased, the various dose received healthy tissue volume also increased. Conclusions: VMAT plan can reduce the risk of secondary malignancy while treating different sites of cancer. VMAT is the most appropriate technique than IMRT, especially in the treatment of large tumor volume. Special attention has to be given, especially while treating women and children. [ABSTRACT FROM AUTHOR]

The prognosis of childhood cancers has improved markedly, and the proportion of long-term survivors has increased in recent years. However, with the increase in the number of long-term survivors, the development of latent treatment-related adverse effects, such as secondary malignancies, has generated new problems. Secondary cancer is defined as a histologically distinct malignancy that develops at least 2 months after the completion of treatment for primary cancer. Genetic factors and acquired conditions associated with treatment modalities are possible causes of secondary malignancy development. Genetic factors include the presence of Li-Fraumeni syndrome (LFS) and retinoblastoma. In terms of acquired factors, radiation and chemotherapy have been reported to be the most strongly associated with secondary malignancy development. The use of alkylating agents and topoisomerase II inhibitors for the treatment of childhood cancer increases the subsequent risk of secondary tumors. We herein investigated three cases of secondary osteosarcoma several years after treatment for primary cancer. In the three patients, the familial history did not appear to fit the clinical diagnostic criteria of LFS or retinoblastoma. The patients had not received previous radiation therapy to the anatomical site of the secondary cancer. However, high dosages of alkylating agents and topoisomerase II inhibitors had been administered for the treatment of primary cancer. The exact link between chemotherapy and secondary cancer remains elusive, but the possibility of an association should be considered. Following the development of multidisciplinary therapies, long-term follow-up and monitoring of latent adverse effects may be necessary for childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Abstract Introduction Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Methods Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV‐CT), megavoltage electronic portal image (MV‐EPI) and megavoltage cone‐beam computed tomography (MV‐CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. Results The highest contralateral breast mean dose was from the MV‐CBCT (1.79 Gy), followed by MV‐EPI (0.22 Gy) and MV‐CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation‐induced secondary cancer to the contralateral breast decreases. MV‐CBCT showed a stronger relationship between breast size and LAR of developing a radiation‐induced contralateral breast cancer in comparison with the MV‐CT and MV‐EPI. Conclusions For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account.

Background: Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. The aim of this study was to estimate and compare the lifetime risk of radiation-induced secondary cancer in pediatric medulloblastoma patients using three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT).Materials and Methods: 3D-CRT and IMRT plans were performed for 10 CSI pediatric patients. The average absorbed doses for organs at risk (OARs) was calculated from dose-volume histograms on the treatment planning system. The average lifetime risk of radiation-induced secondary cancer was then calculated.Results: Lifetime risk of secondary cancer for CSI pediatric patients treated using IMRT decreases in some OARs compared with those treated using 3D-CRT. This is attributable to the decrease in the average absorbed dose in some OARs when using IMRT technique.Conclusion: Follow-up of medulloblastoma pediatric patients should be performed after ending the treatment course in order to diagnose early secondary tumors. IMRT technique is substantially better than 3D-CRT in terms of lifetime risk of radiation-induced secondary cancer, probably due to reduced dose to OARs especially to the thyroid, which is the most sensitive organ to radiation. [ABSTRACT FROM AUTHOR]

Background: The risk of developing secondary cancers (SCs) among patients with malignant thymoma in the US has not been estimated in the more recent time period. Methods: We extracted demographic and treatment data from the SEER database to estimate the standardized incidence ratios (SIRs). Results: Of 1570 patients with thymoma 211 (13.4%) had SCs. The overall risk of developing SCs was higher among patients with thymoma (SIR: 1.54, 95% CI: 1.34-1.76). The SIRs for cancers of lung, esophagus, sigmoid colon, soft tissue and heart, kidney, NHL and leukemia was significantly higher as compared to the general US population. Conclusions: Patients with thymoma are at modestly elevated risk of developing SCs as compared to the general US population. Although the overall risk has not changed after 14 additional years of follow up, the distribution of SCs has significantly broadened, with increased diversity across type and anatomic location of SCs. [ABSTRACT FROM AUTHOR]

Elective nodal irradiation ( ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation ( CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus two concurrent cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis. Of these patients, 51 were treated with ENI, whereas 38 were treated with CFI. For the per-protocol population, the patients in the ENI group significantly improved in terms of their 10-year disease-specific overall survival (43.1% vs 10.5%, P = 0.019), 10-year disease-free survival (36.7% vs 10.2%, P = 0.040) and 10-year local recurrence-free survival (47.2% vs 17.2%, P = 0.018) compared with the CFI group. Aside from radiation esophagitis, the incidence of grade 3 or greater acute toxicities did not differ between the two groups. Multivariate analysis showed that radiation field, tumor length and clinical stage were independent prognostic factors associated with OS. Concurrent chemoradiotherapy with ENI improves both disease-specific overall survival and loco-regional control in patients with inoperable esophageal cancer receiving per-protocol treatment. The regimen has a manageable tolerability profile. [ABSTRACT FROM AUTHOR]