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We examined associations between modifiable and nonmodifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years postdiagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray subdistribution hazard models. During a median follow-up of 16.7 years (IQR, 12.2-17.9), 89 (17%) participants developed an SPC; breast (29%), colorectal (13%), and lung (12%) cancers were the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs < 90.4 g/day: subhazard ratio [sHR] = 1.71; 95% CI, 1.09-2.69), as well as older age (≥60 vs < 60 years: sHR = 2.48; 95% CI, 1.34-4.62) and alcohol intake (≥2 drinks/week vs none: sHR = 3.81; 95% CI, 1.55-9.31) during early survivorship, were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR = 0.34; 95% CI, 0.14-0.82). With 1 in 6 survivors developing an SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors. This article is part of a Special Collection on Gynecological Cancer. [ABSTRACT FROM AUTHOR]

Abstract Second Primary Cancers (SPCs) are defined as cancers that develop either simultaneously or metachronously in the same individual who has been diagnosed with and survived one primary cancer. SPCs exhibit a high incidence rate and represent the primary cause of mortality among survivors of first primary cancers. There is growing concern about the dangers of SPCs. This review summarizes recent studies on the mechanisms of SPCs, including the roles of genomic changes after first primary cancer (FPC) treatments, stromal cell phenotypic and metabolic changes, hormone levels and receptor expression, immunosuppression, aberrant gene methylation, EGFR signaling, and cell-free DNA in SPC development. This comprehensive analysis contributes to elucidating current research trends in SPC mechanisms and enhances our understanding of the underlying pathophysiology. Furthermore, potential applications of intratumoral microbes, single-cell multi-omics, and metabolomics in investigating SPC mechanisms are also discussed, providing new ideas for follow-up studies.

Predicting and improving the response of rectal cancer to second primary cancers (SPCs) remains an active and challenging field of clinical research. Identifying predictive risk factors for SPCs will help guide more personalized treatment strategies. In this study, we propose that experience data be used as evidence to support patient-oriented decision-making. The proposed model consists of two main components: a pipeline for extraction and classification and a clinical risk assessment. The study includes 4402 patient datasets, including 395 SPC patients, collected from three cancer registry databases at three medical centers; based on literature reviews and discussion with clinical experts, 10 predictive variables were considered risk factors for SPCs. The proposed extraction and classification pipelines that classified patients according to importance were age at diagnosis, chemotherapy, smoking behavior, combined stage group, and sex, as has been proven in previous studies. The C5 method had the highest predicted AUC (84.88%). In addition, the proposed model was associated with a classification pipeline that showed an acceptable testing accuracy of 80.85%, a recall of 79.97%, a specificity of 88.12%, a precision of 85.79%, and an F1 score of 79.88%. Our results indicate that chemotherapy is the most important prognostic risk factor for SPCs in rectal cancer survivors. Furthermore, our decision tree for clinical risk assessment illuminates the possibility of assessing the effectiveness of a combination of these risk factors. This proposed model may provide an essential evaluation and longitudinal change for personalized treatment of rectal cancer survivors in the future. [ABSTRACT FROM AUTHOR]

Background Annual surveillance mammography is recommended for women with a personal history of breast cancer. Risk prediction models that estimate mammography failures such as interval second breast cancers could help to tailor surveillance imaging regimens to women's individual risk profiles. Methods In a cohort of women with a history of breast cancer receiving surveillance mammography in the Breast Cancer Surveillance Consortium in 1996-2019, we used Least Absolute Shrinkage and Selection Operator (LASSO)-penalized regression to estimate the probability of an interval second cancer (invasive cancer or ductal carcinoma in situ) in the 1 year after a negative surveillance mammogram. Based on predicted risks from this one-year risk model, we generated cumulative risks of an interval second cancer for the five-year period after each mammogram. Model performance was evaluated using cross-validation in the overall cohort and within race and ethnicity strata. Results In 173 290 surveillance mammograms, we observed 496 interval cancers. One-year risk models were well-calibrated (expected/observed ratio = 1.00) with good accuracy (area under the receiver operating characteristic curve = 0.64). Model performance was similar across race and ethnicity groups. The median five-year cumulative risk was 1.20% (interquartile range 0.93%-1.63%). Median five-year risks were highest in women who were under age 40 or pre- or perimenopausal at diagnosis and those with estrogen receptor-negative primary breast cancers. Conclusions Our risk model identified women at high risk of interval second breast cancers who may benefit from additional surveillance imaging modalities. Risk models should be evaluated to determine if risk-guided supplemental surveillance imaging improves early detection and decreases surveillance failures. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and meta-analysis aimed to examine the risk of second primary cancers (SPCs) among retinoblastoma (Rb) patients, both hereditary and nonhereditary. Previous studies have reported on the long-term risk of SPCs in these patient populations, but a comprehensive synthesis of the existing evidence is lacking. Methods: A systematic search was conducted in PubMed, EMBASE, and Cochrane Library from inception to 12 March 2023, supplemented by manual screening. Eligible studies were identified, and data were extracted. The primary outcome measure was the standardized incidence ratios (SIRs) of SPCs in Rb patients. Summary estimates were calculated using random or fixed effects models. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: Ten studies, including nine high-quality studies, were included in this review. The summary estimate of SIR for SPCs among hereditary Rb patients was 17.55 (95% CI=13.10-23.51), while the pooled estimate of SIR for SPCs among nonhereditary Rb patients was 1.36 (95% CI=0.90-2.04). Significant differences in SIRs for different SPC types were observed (P=0.028), including nasal cavity tumor (SIR=591.06, 95% CI=162.79-2146.01), bone tumor (SIR=442.91, 95% CI=191.63-1023.68), soft tissue sarcoma (SIR=202.93, 95% CI=114.10-360.93), CNS (SIR=12.84, 95% CI=8.80-18.74), and female breast cancer (SIR=3.68, 95% CI=2.52-5.37). Chemotherapy and radiation therapy were associated with an increased risk of SPCs among hereditary Rb patients. Discussion: The findings of this review indicate that hereditary Rb patients have a significantly elevated risk of developing SPCs, whereas nonhereditary Rb patients do not show the same risk. Furthermore, significant differences were observed in the SIRs of different SPC types. Treatment techniques, specifically chemotherapy and radiation therapy, were associated with an increased risk of SPCs among hereditary Rb patients. These findings highlight the importance of radiation protection for Rb patients and the need for further research and tailored management strategies for this high-risk population. [ABSTRACT FROM AUTHOR]

Objective To analyze the risk and prognostic factors for synchronous breast cancer（BC）and thyroid cancer（TC）. Methods The Surveillance，Epidemiology，and End Results Program（SEER）2020 database was utilized to collect the information of patients with synchronous BC and TC（BC and TC group）and those with BC alone（BC group）. Clinical data and survival were compared between two groups. Clinical data of patients with synchronous BC and TC（BC and TC group A）and those with BC alone（BC group B）admitted to a certain hospital were retrospectively analyzed. Clinical data and survival were also compared between two groups. Results ①Analysis of SEER database ，482 patients in BC and TC group and 500 patients in BC group. Univariate analysis revealed that age at first diagnosis and progesterone receptor（PR）were the risk factors for synchronous BC and TC（both P < 0.05）. Multivariate analysis found that age at first diagnosis（OR=1.800，95% CI：1.387-2.337，P < 0.001）and PR（OR=1.364，95% CI：1.023-1.818，P = 0.034）were the independent risk factors for synchronous BC and TC. Excluding those with incomplete follow-up data，univariate analysis indicated that tumor diameter and PR were the prognostic factors for synchronous BC and TC（both P < 0.05）；multivariate analysis revealed that tumor diameter was an independent prognostic factor for synchronous BC and TC（OR=4.328，95% CI：1.410-13.288，P = 0.010）. Univariate analysis found that age at first diagnosis and tumor diameter were the prognostic factors for BC alone（both P < 0.05）；multivariate analysis identified that age at first diagnosis（OR = 2.443，95% CI ：1.014-5.889，P = 0.047）and tumor diameter（OR = 2.030，95% CI：1.039-3.969，P = 0.038）were the independent prognostic factors for BC alone. ②Analysis of inpatients，there were 40 patients each in BC and TC group A and BC group A. Univariate analysis indicated that menstrual status，PR，proliferation index Ki-67，and TT3 were the risk factors for synchronous BC and TC（all P < 0.05），multivariate analysis found that menstrual status（synchronous BC and TC versus BC alone，OR=0.175，95% CI：0.052-0.591，P = 0.005），PR（OR=5.686，95% CI：1.677-19.282，P = 0.005），Ki-67（OR=3.966，95% CI：1.133-13.875，P = 0.031）were the independent risk factors for synchronous BC and TC. Eighty patients were subject to follow-up，6 patients died，27 survived，and 7 were lost to follow-up in BC and TC group A；2 patients died，29 survived，and 9 were lost to follow-up in BC group A. Cox regression analysis revealed no statistical significance in both groups. Conclusions Age at first diagnosis，menstrual status，PR，and Ki-67 are the risk factors for synchronous BC and TC. Tumor diameter is an independent prognostic factor for synchronous BC and TC. Age at first diagnosis and tumor diameter are the independent prognostic factors for BC alone.

Cancer survivors have an increased risk of developing subsequent primary tumors. However, the characteristics of first primary cancers (FPCs) with various types of second primary cancers (SPCs) are poorly understood, which hinders screening strategies. We analyzed data from 1,893,258 patients from the Surveillance, Epidemiology, and End Results (SEER) database to characterize and classify of FPC patients with subsequent SPCs at the pan-cancer level. In total, 3% of patients had SPC, with varied incidence rates observed depending on the types of FPC. Their onset patterns of SPC and diversity of SPC varied. Based on the diversity of the high-incidence sites of SPC, we classified FPCs into two categories: FPCs that require whole-body screening and those that need screening of particular body parts. Moreover, according to the different timing of high incidence of SPCs, our system classifies FPCs into two subtypes: FPCs that require long-term monitoring for the occurrence of SPCs and those that require screening at specific time points for SPCs. Furthermore, we identified 11 anatomical sites where over half of FPC types are prone to SPC occurrence at these locations. The risk factors for SPC occurrence in different FPC types and prognostic factors were also elucidated. Overall, we characterize and classify of FPC patients with subsequent SPCs at the pan-cancer level, which can guide the development of distinct screening strategies for each FPC type. [ABSTRACT FROM AUTHOR]

Background/purpose: As the occurrence of second primary cancers (SPCs) is strongly related to the survival rate of patients with oral and pharyngeal cancers, early detection and treatment are important. Therefore, this study aimed to clarify the incidence of SPCs and their risk factors in patients with oral and pharyngeal cancer. Materials and methods: This observational study was conducted using data from the administrative claims database of 21,736 participants with oral and pharyngeal cancer from January 2005 to December 2020. We evaluated the cumulative incidence of SPCs among patients with oral and pharyngeal cancers using the Kaplan–Meier method. The Cox proportional-hazard model was used for multivariate analysis. Results: Of the 1633 patients with oral and pharyngeal cancer who qualified for analysis, 388 developed SPCs (incidence rate, 7.994/1000 person-months). The multivariate analysis showed that the risk of developing SPCs was affected by age at diagnosis of oral and pharyngeal cancer, cancer treatment, and anatomical site of the primary cancer. Conclusion: Patients with oral and pharyngeal cancers are at a high risk of developing SPCs. The data from this study may be useful in providing accurate information to patients with oral and oropharyngeal cancer.

Approximately 5–20% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (α-tocopherol, β-carotene, JP, Isotretinoin, interferon α-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context. [ABSTRACT FROM AUTHOR]

There is an increased risk of second primary cancers (SPCs) after neuroendocrine tumor (NET) diagnosis. The clinical significance of SPCs in this population is unknown. The purpose of this study was to evaluate the association between SPCs after NET diagnosis and survival. We performed a population-based, retrospective cohort study of NET patients (gastrointestinal, pancreatic, or lung primary) from 2000 to 2016 using the Surveillance, Epidemiology, and End Results database. Cox regression models assessed the association between SPCs and NET-specific (NET-SS), cancer-specific (CSS), and overall survival (OS). Of 58,553 NET patients, 7.9% experienced an SPC. SPCs were associated with worse OS (hazard ratio (HR) 2.14, 95% CI 1.94-2.36) and CSS (HR 2.31, 95% CI 2.06-2.59) with no difference in NET-SS (HR 1.04, 95% CI 0.87-1.23). Stratified analyses by histologic grade showed similar results for well and moderately differentiated NETs, but no difference in OS or CSS for poorly differentiated NETs (P > 0.05). In stratified analyses by NET site, SPCs were associated with worse OS (HR 3.41, 95% CI 3.01-3.87) and CSS (HR 4.96, 95% CI 4.28-5.74) in gastrointestinal NETs and worse OS (HR 1.25, 95% CI 1.03-1.52) with no difference in CSS (HR 1.08, 95% CI 0.85-1.36) in lung NETs. SPCs were not associated with a difference in OS or CSS in pancreatic NETs (P > 0.05). In conclusion, SPCs after NETs were associated with inferior OS and CSS compared to no SPC but were not associated with NET-SS. These data highlight the need for long-term follow-up in NETs to include the detection of SPCs to ensure early diagnosis and timely management. [ABSTRACT FROM AUTHOR]

Abstract Background The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. Methods Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. Results APL occurred in 374 males and 387 females at a median age of 44 (1–97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991–2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14–161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010–2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. Conclusions There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).

As the occurrence of second primary cancers (SPCs) is strongly related to the survival rate of patients with oral and pharyngeal cancers, early detection and treatment are important. Therefore, this study aimed to clarify the incidence of SPCs and their risk factors in patients with oral and pharyngeal cancer. This observational study was conducted using data from the administrative claims database of 21,736 participants with oral and pharyngeal cancer from January 2005 to December 2020. We evaluated the cumulative incidence of SPCs among patients with oral and pharyngeal cancers using the Kaplan–Meier method. The Cox proportional-hazard model was used for multivariate analysis. Of the 1633 patients with oral and pharyngeal cancer who qualified for analysis, 388 developed SPCs (incidence rate, 7.994/1000 person-months). The multivariate analysis showed that the risk of developing SPCs was affected by age at diagnosis of oral and pharyngeal cancer, cancer treatment, and anatomical site of the primary cancer. Patients with oral and pharyngeal cancers are at a high risk of developing SPCs. The data from this study may be useful in providing accurate information to patients with oral and oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Purpose: To assess oncological outcomes of patients receiving neoadjuvant radiochemotherapy (RCT) for soft tissue sarcoma (STS) of the extremities. Methods: Patients who were treated with preoperative radiotherapy and concomitant chemotherapy—3 cycles of mitomycin/doxorubicin/cisplatin (MAP) or 2–4 cycles of doxorubicin/cisplatin (AP)—followed by surgery were analyzed retrospectively. Survival rates were estimated, and prognostic factors were identified. Results: Between 1994 and 2017, a total of 108 patients were included. Median ages were 43 years and 51 years for patients receiving MAP and AP, respectively. The 5‑year local relapse-free survival (LRFS), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were 94.1, 63.6, 75.3, and 71.9%, respectively. In the multivariate analysis, significant predictors were identified as follows: de novo or R1/R2 resected tumor on admission before RCT (p = 0.017; hazard ratio [HR] 0.112, 95% confidence interval [CI] 0.019–0.675) and R0 resection after RCT (p = 0.010; HR 0.121, 95% CI 0.024–0.598) for LRFS; female gender (p = 0.042; HR 0.569, 95% CI 0.330–0.979) and liposarcoma histology (p = 0.014; HR 0.436, 95% CI 0.224–0.845) for DFS; liposarcoma histology (p = 0.003; HR 0.114, 95% CI 0.027–0.478) and AP regimen (p = 0.017; HR 0.371, 95% CI 0.165–0.836) for DSS; age ≤ 45 years (p = 0.043; HR 0.537, 95% CI 0.294–0.980) and liposarcoma histology (p = 0.006; HR 0.318, 95% CI 0.141–0.716) for OS, respectively. Conclusion: An increased risk for local failure seems to exist for patients with relapsed tumor on admission and having positive surgical margins after neoadjuvant RCT. Intensity of chemotherapy influenced DSS but not OS, which could be due to younger patients receiving MAP. [ABSTRACT FROM AUTHOR]

Background: The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. Methods: Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. Results: APL occurred in 374 males and 387 females at a median age of 44 (1–97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991–2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14–161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010–2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. Conclusions: There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754). [ABSTRACT FROM AUTHOR]

Abstract Objective Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims to compare the clinical manifestation, pathology, treatment, and prognostic features of patients with 2nd RCC and first primary renal cell carcinoma (1st RCC). Materials and methods Data of the patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. Results The most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fewer had clinical symptoms and renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs were commonly identified in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. Conclusions Second RCC is not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately.

Simple Summary: In head and neck cancer surgery, blood transfusion is required occasionally due to patients' underlying conditions and perioperative blood loss during surgical resection. However, transfusion is associated with immunosuppression, also known as the term "transfusion-related immune modulation (TRIM)", which could lead to worse cancer prognoses. The purpose of the study is to assess the association between perioperative blood transfusion and head and neck cancer recurrence and mortality. Our findings showed that blood transfusion was significantly associated with both cancer recurrence and mortality after head and neck cancer surgery. Background: The association between perioperative blood transfusion and cancer prognosis in patients with head and neck cancer (HNC) receiving surgery remains controversial. Methods: We designed a retrospective observational study of patients with HNC undergoing tumor resection surgery from 2014 to 2017 and followed them up until June 2020. An inverse probability of treatment weighting (IPTW) was applied to balance baseline patient characteristics in the exposed and unexposed groups. COX regression was used for the evaluation of tumor recurrence and overall survival. Results: A total of 683 patients were included; 192 of them (28.1%) received perioperative packed RBC transfusion. Perioperative blood transfusion was significantly associated with HNC recurrence (IPTW adjusted HR: 1.37, 95% CI: 1.1–1.7, p = 0.006) and all-cause mortality (IPTW adjusted HR: 1.37, 95% CI: 1.07–1.74, p = 0.011). Otherwise, there was an increased association with cancer recurrence in a dose-dependent manner. Conclusion: Perioperative transfusion was associated with cancer recurrence and mortality after HNC tumor surgery. [ABSTRACT FROM AUTHOR]

Approximately 5–20% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (α-tocopherol, β-carotene, JP, Isotretinoin, interferon α-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context.

Background: Breast cancer (BC) survivors have an increased risk of developing second primary cancers (SPCs); however, it is still unclear if metastasis is a risk factor for developing SPCs. Usually, long-term cancer survivors face an increased risk of developing SPCs; however, less attention has been paid to SPCs in patients with metastatic cancer as the survival outcomes of the patients are greatly reduced. Methods: A total of 17,077 American women diagnosed with breast cancer between 2010 and 2018 were identified from Surveillance, Epidemiology, and End Results (SEER) database and were included in the study. The clinical characteristics, standardized incidence ratio (SIR), standardized mortality ratio (SMR), and patterns of SPCs in BC patients with no metastasis, regional lymph node metastasis, and distant metastasis were investigated. Kaplan-Meier method was used to compare the prognosis of BC patients after developing SPCs with different metastatic status. XGBoost, a high-precision machine learning algorithm, was used to create a prediction model to estimate the prognosis of metastatic breast cancer (MBC) patients with SPCs. Results: The results reveal that the SIR (1.01; 95% CI, 0.99-1.03, p>0.05) of SPCs in non-metastasis breast cancer (NMBC) patients was similar to the general population. Further, patients with regional lymph node metastasis showed an 8% increased risk of SPCs (SIR=1.08, 95%CI, 1.05-1.11, p<0.05), and patients with distant metastasis had a 26% increased risk of SPCs (SIR=1.26, 95%CI, 1.16-1.37, p<0.05). The SIR of SPCs in all patients below the age of 40 was the highest, which decreased with age. Patients with poorly differentiated cancers, large tumor size, and late N stage had an increased risk of SPCs. However, an increase in SIR of SPCs was observed in distant MBC patients, even at the early T1 (SIR=1.60, 95% CI, 1.22-1.98, p<0.05) and N1 (SIR=1.27, 95% CI, 1.10-1.44, p<0.05) stage. An increase in the SIR of SPCs was observed in patients with triple-negative BC, and the SIR of SPC increased with metastasis development in BC patients with luminal A subtype. The peak of SPCs risk occurrence was earlier in MBC patients (4-6 months and 10 months) compared to NMBC patients (12 months). The effect of metastasis on the prognosis of SPCs patients was dependent on the type of SPCs. Meanwhile, the XGBoost model was created to predict the 3-year (AUC=0.873) and 5-year survival (AUC=0.918) of SPCs in MBC patients. Conclusions: Our study provides novel insight into the impact of metastasis on SPCs in BC patients. Metastasis could promote the second primary tumorigenesis which further increased cancer-related deaths. Therefore, more attention should be paid to the occurrence of SPCs in MBC patients. [ABSTRACT FROM AUTHOR]

Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan's National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged <65 years accounted for 53.15%. Patients aged ≥65 years accounted for 40.18% and 53.24% in the SPLC and SPEC groups, respectively. Females accounted for 50.3% of patients without SPC, 54% of the SPLC group, and 44.3% of the SPEC group. Univariate and multivariate Cox proportional hazard models showed increased hazard ratios for smoking, hypertension, and diabetes mellitus, and lower HRs for surgery, chemotherapy, radiotherapy, and TKIs. Patients undergoing surgery, chemotherapy, and radiotherapy were associated with a lower risk of SPCs. Treatment with EGFR TKIs was a significant and independent factor associated with lower incidence of SPCs. This study may encourage researchers to establish predictive models based on our results to assess the risk factors for SPCs, and therefore, early screening and intervention could be applied, and the SPCs-related mortality and relevant medical costs could be reduced. [ABSTRACT FROM AUTHOR]

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004–2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypolipidemic drugs are among the most frequently prescribed medications in the Western world. Since many studies have indicated their role in carcinogenesis, this work aimed to investigate their association with the occurrence of a second primary malignancy in colorectal cancer survivors. The overall incidence of a second neoplasm was not linked to hypolipidemic medication; however, a subgroup analysis revealed a lower incidence of secondary neoplasia in statin users. When stratified by cancer types, a significant increase in gastric and bladder cancer was detected among colorectal cancer patients using hypolipidemic drugs. Survival outcomes in patients with early-stage colorectal carcinoma who suffered second cancer were significantly worse if treated with hypolipidemic drugs. Although our results do not provide evidence for a causative relationship between hypolipidemic medication and carcinogenesis, these correlations might steer the direction of tertiary prevention care towards specific risk factors shared between cardiovascular diseases and cancer. An increasing number of studies has brought evidence of the protective role of statin use against different types of cancer. However, data on their association with second primary malignancies (SPMs) are lacking. The purpose of this study was to determine the role of hypolipidemic treatment in the prevention of second primary cancer in colorectal cancer (CRC) survivors. We conducted a retrospective single-institution study of 1401 patients with newly diagnosed colorectal cancer from January 2003 to December 2016, with follow-up until December 2020. An SPM was detected in 301 patients (21%), and the incidence was significantly lower in patients with statin medication. However, stratification by cancer types revealed an increased incidence of bladder and gastric cancer in hypolipidemic users. A Kaplan−Meier analysis of early-stage CRC survivors with an SPM showed a significant survival benefit in patients without a history of hypolipidemic treatment. Despite the protective role of statins on overall second cancer incidence, these data indicate that CRC survivors treated with hypolipidemic drugs should be screened more cautiously for SPMs, especially for gastric and bladder cancer. [ABSTRACT FROM AUTHOR]

Objective: Second primary renal cell carcinoma (2nd RCC) refers to renal cell carcinoma (RCC) diagnosed after another unrelated malignancy. This study aims to compare the clinical manifestation, pathology, treatment, and prognostic features of patients with 2nd RCC and first primary renal cell carcinoma (1st RCC). Materials and methods: Data of the patients with localized RCC were retrospectively collected. They were classified as 2nd RCC or 1st RCC according to a previously diagnosed cancer, including 113 cases of 2nd RCC and 749 cases of 1st RCC. Results: The most common types of extrarenal malignancies in patients with 2nd RCC include lung, colorectal, breast, gynecological, and gastric cancers. The age and smoking rate of 2nd RCC patients were significantly higher than in those of 1st RCC patients. For 2nd RCC patients, fewer had clinical symptoms and renal masses tend to be smaller. One hundred and eight (95.6%) patients with 2nd RCC received surgical interventions. All patients with 1st RCC underwent renal surgery. More patients with 2nd RCC underwent a partial nephrectomy. Pathologically, there was no significant difference in postoperative pathological types between the 2nd and 1st RCCs. However, the 2nd RCCs were commonly identified in the early stages. The median overall survival (OS) of 2nd RCC patients was 117 months, which was shorter than that of 1st RCC patients. Conclusions: Second RCC is not uncommon. More attention should be paid to screening for 2nd RCC in cancer survivors. There are some differences between patients with 2nd and 1st RCCs that should be viewed separately. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improvements in cancer survival mean that an increasing number of survivors may live long enough beyond their initial cancer to be diagnosed with additional independent primary cancers. The proportion of newly diagnosed cancers that are second‐ or higher‐order primaries and how this proportion has changed over the past several decades were examined. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify incident malignant primaries diagnosed between 1975 and 2017. Using the SEER sequence number, the authors tabulated the proportion of all cancers in each calendar year that were second‐ or higher‐order primaries. The average annual percent change (AAPC) was then calculated to assess how this proportion has changed over time. RESULTS: Analyses included nearly 4.9 million incident cancers diagnosed during 1975‐2017. The proportion of all cancers that were second‐ or higher‐order increased steadily from 9.77% during 1975‐1984 to 21.03% during 2015‐2017, reflecting an AAPC of 2.41% (95% CI, 2.16%‐2.65%). In 2015‐2017, second‐ or higher‐order cancers were most prevalent among cancers of the bladder (28.79%), followed by lung and bronchus (28.07%), melanoma (27.88%), and leukemia (26.10%). The highest AAPCs over the study period were observed for melanoma (4.05%), leukemia (3.51%), and lung and bronchus (3.36%). CONCLUSIONS: The proportion of newly diagnosed cancers that are second‐ or higher‐order has grown rapidly over the past several decades and currently exceeds 20%. Continued monitoring of second and later primaries will be critical for anticipating the future impact on cancer treatment and survivorship care. In the United States, the proportion of newly diagnosed cancers that are second‐ or higher‐order has grown rapidly over the past several decades and currently exceeds 20%. Because the challenges associated with 2 or more primary cancer diagnoses may be substantial and unique, continued monitoring of second‐ or higher‐order cancers will be critical for anticipating the future impact on cancer treatment and survivorship care. [ABSTRACT FROM AUTHOR]

Proton therapy has been proposed as a technique to improve the long-term quality of life of breast cancer patients. This is due to its ability to reduce the dose to healthy tissue compared to conventional X-ray therapy. The aim of this study was to investigate the risk of secondary carcinogenesis due to proton therapy compared to hybrid IMRT for breast treatments. In this study, the Pinnacle treatment planning system was used to simulate treatment plans for 15 female left-sided whole breast cancer patients with deep inspiration breath hold scans. Two treatment plans were generated for each patient: hybrid intensity modulated radiotherapy (h-IMRT) and intensity modulated proton therapy (IMPT). Using the dose-volume histograms (DVHs) from these plans, the mean lifetime attributed risk (LAR) for both lungs and the contralateral breast were evaluated using the BEIR VII and Schneider full risk models. The results from both risk models show lower LAR estimates for the IMPT treatment plan compared to the h-IMRT treatment plan. This result was observed for all organs of interest and was consistent amongst the two separate risk models. For both treatment plans, the organs from most to least at risk were: ipsilateral lung, contralateral breast, and contralateral lung. In all cases, the risk estimated via the BEIR VII model was higher that the Schneider full risk model. The use of proton therapy for breast treatments leads to reduced risk estimates for secondary carcinogenesis. Therefore, proton therapy shows promise in improving the long term treatment outcome of breast patients. [ABSTRACT FROM AUTHOR]

Survivors of gynecologic cancers have an increased risk of developing second primary cancers (SPC); however it is unclear which sites have higher risks. We aimed to ascertain risk of SPC among survivors of gynecological cancer, and identify anatomic sites at risk of SPC. We queried the Surveillance, Epidemiology and End Results database (2000–2016) for confirmed cases of index gynecological (cervix uteri [cervical], corpus and uterus [endometrial], ovarian, vaginal, and vulvar) cancers. Risk of SPC was estimated using standardized incidence ratios (SIRs: observed/expected cases) and excess absolute risks (EARs: observed - expected cases) per 10,000 person-years at risk (PYR). SIRs and EARs were stratified by index anatomic site and latency interval. Among the cohort of 301,210 gynecological cancer survivors, 19,005 (6.31%) developed an SPC (SIR = 1.16; 95% CI, 1.15–1.18 and EAR = 17.2 cases per 10,000 PYR) compared with the general population. All gynecological cancer survivors (except survivors of ovarian) had a significant risk of developing SPC (SIR range 1.06–2.16), with survivors of vulvar cancer having the highest risk (SIR = 2.16; 95% CI, 2.06–2.27; EAR = 139.5 per 10,000 PYR). Risk of SPC was highest within the first 5 years post-diagnosis for survivors of cervical, vulvar and vaginal cancers. While most index gynecological cancer sites are associated with increased risk of SPC, risk is highest among survivors of vulvar cancer. These findings have the potential to inform lifelong surveillance recommendations for gynecological cancer survivors. • Quantified the risks of second primary cancer (SPC) in patients diagnosed with first primary gynecological cancers. • 1-in-15 patients diagnosed with first primary gynecological cancers developed an SPC. • Patients diagnosed with first primary vulvar cancer had the highest risk of SPC. • The risk of SPC remain high for the first five years after the initial diagnosis of first primary gynecological cancers. [ABSTRACT FROM AUTHOR]

Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.

Purpose: The current study explored the risk of developing second primary cancers (SPCs) among long-term early-stage breast cancer survivors and identified risk factors to build an externally validated clinical prediction model.Methods: The cumulative incidence of SPCs was calculated by Gray method among survivors of early-stage initial primary breast cancer (IPBC). Comparisons of treatment-related risk by selected organ sites were performed. A nomogram was established to estimate the individual risk of developing SPCs based on the multivariate Fine and Gray risk model. Decision curve analysis (DCA) was used to evaluate clinical usefulness of the model.Results: The cumulative incidence of developing SPCs after early-stage IPBC was 7.43% at 10 years, 14.41% at 15 years, and 20.08% at 20 years. Radiotherapy was associated with elevated risks of any SPCs and with elevated risks of lung cancer (SHR: 1.109; P = 0.045), breast cancer (SHR: 1.389; P < 0.001), and AML (SHR: 1.298; P = 0.045). Chemotherapy was significantly associated with a declined risk of any SPCs, with decreased risks of lung (SHR: 0.895; P = 0.015) and breast cancers (SHR: 0.891; P < 0.001), as well as elevated risks of other leukemias (SHR: 1.408; P = 0.002). HR-positive status was associated with decreased risks of any SPCs; with decreased risks of breast (SHR: 0.842; P < 0.001) and ovarian cancers (SHR: 0.483; P < 0.001); and with elevated risks of urinary tract cancers (SHR: 1.214; P = 0.029).Conclusion: We found that the cumulative incidence of developing SPCs increased over time and did not plateau. Risk factors for developing SPCs identified by our study were not consistent with those of previous studies. The prediction model can help identify individuals at higher risk of SPCs.

Purpose: The current study explored the risk of developing second primary cancers (SPCs) among long-term early-stage breast cancer survivors and identified risk factors to build an externally validated clinical prediction model. Methods: The cumulative incidence of SPCs was calculated by Gray method among survivors of early-stage initial primary breast cancer (IPBC). Comparisons of treatment-related risk by selected organ sites were performed. A nomogram was established to estimate the individual risk of developing SPCs based on the multivariate Fine and Gray risk model. Decision curve analysis (DCA) was used to evaluate clinical usefulness of the model. Results: The cumulative incidence of developing SPCs after early-stage IPBC was 7.43% at 10 years, 14.41% at 15 years, and 20.08% at 20 years. Radiotherapy was associated with elevated risks of any SPCs and with elevated risks of lung cancer (SHR: 1.109; P = 0.045), breast cancer (SHR: 1.389; P < 0.001), and AML (SHR: 1.298; P = 0.045). Chemotherapy was significantly associated with a declined risk of any SPCs, with decreased risks of lung (SHR: 0.895; P = 0.015) and breast cancers (SHR: 0.891; P < 0.001), as well as elevated risks of other leukemias (SHR: 1.408; P = 0.002). HR-positive status was associated with decreased risks of any SPCs; with decreased risks of breast (SHR: 0.842; P < 0.001) and ovarian cancers (SHR: 0.483; P < 0.001); and with elevated risks of urinary tract cancers (SHR: 1.214; P = 0.029). Conclusion: We found that the cumulative incidence of developing SPCs increased over time and did not plateau. Risk factors for developing SPCs identified by our study were not consistent with those of previous studies. The prediction model can help identify individuals at higher risk of SPCs. [ABSTRACT FROM AUTHOR]

The article discusses the cancer risk following post-transplant lymphoproliferative disorders in solid organ transplant recipients. Topics include how post-transplant lymphoproliferative disorders (PTLDs) are associated with immunosuppressive therapy administered to prevent graft rejection, leading to uncontrolled replication of Epstein–Barr virus (EBV).

Background: It is unclear whether the established association between cutaneous melanoma (CM) and lymphoid neoplasms (LNs) differs across LN subtypes. This study quantifies risk for developing CM after specific LNs and, conversely, for developing specific LNs after CM, as well as assessing clinical impact.Methods: We identified a cohort of Caucasian adults (age 20-83 years) initially diagnosed with CM or LN, as reported to 17 US population-based cancer registries, 2000-2014. Standardized incidence ratios (SIRs) quantified second cancer risk. We assessed impact of second cancer development on risk of all-cause mortality using Cox regression.Results: Among 151 949 one-or-more-year survivors of first primary LN, second primary CM risk was statistically significantly elevated after chronic lymphocytic leukemia/small lymphocytic lymphoma (SIR = 1.96, 95% confidence interval [CI] = 1.74 to 2.21), follicular lymphoma (SIR = 1.32, 95% CI = 1.09 to 1.58), and plasma cell neoplasms (SIR = 1.33, 95% CI = 1.07 to 1.63). Risks for these same subtypes were statistically significantly elevated among 148 336 survivors of first primary CM (SIR = 1.44, 95% CI = 1.25 to 1.66; SIR = 1.47, 95% CI = 1.21 to 1.77; SIR = 1.25, 95% CI = 1.06 to 1.47; respectively). Risk for CM was statistically significantly elevated after diffuse large B-cell lymphoma (SIR = 1.22, 95% CI = 1.02 to 1.45) and Hodgkin lymphoma (SIR = 1.75, 95% CI = 1.33 to 2.26), but the reciprocal relationship was not observed. There were no statistically significant associations between marginal zone lymphoma and CM. Among survivors of most LN subtypes, CM statistically significantly increased risk of death (hazard ratio [HR] range = 1.52, 95% CI = 1.25 to 1.85, to 2.46, 95% CI = 1.45 to 4.16). Among survivors of CM, LN statistically significantly increased risk of death (HR range = 1.75, 95% CI = 1.15 to 2.65, to 6.28, 95% CI = 5.00 to 7.88), with the highest risks observed for the most aggressive LN subtypes.Conclusions: Heterogeneous associations between CM and specific LN subtypes provide novel insights into the etiology of these malignancies, with the mutual association between CM and certain LN suggesting shared etiology. Development of second primary CM or LN substantially reduces overall survival. [ABSTRACT FROM AUTHOR]

Background: The authors' systematic review indicated an increasing trend in the risk of second primary cancers (SPCs) from the 1980s to 2000 when considering studies from the United States and Australia. It is uncertain whether this trend has continued to increase since 2000.Methods: The current study was a population-based study of 51,802 individuals with adult-onset cancers identified in the Tasmanian Cancer Registry. Patients with a first cancer diagnosis made between 1980 and 2009 were followed up to December 2013. SPC risks were quantified using standardized incidence ratios (SIRs) and absolute excess risks (AERs). Trends in SPC risk were assessed using multivariable Poisson models.Results: With a median follow-up of 4.8 years (mean, 6.9 years), a total of 5339 SPCs were observed. The SIRs for any SPC increased from 0.98 (95% confidence interval, 0.90-1.07) after a first cancer diagnosis in 1980 through 1984 to 1.12 (95% confidence interval, 1.05-1.20) in 2005 through 2009. In multivariable Poisson models accounting for patient sex, age at the time of the first cancer diagnosis, follow-up interval, and first cancer type, the trend in SIRs increased significantly from 1980 through 2009 for all SPCs (P for trend <.001) and for specific SPCs of the head and neck, lung, digestive tract, and prostate (all P for trend <.05). From 2000 onward, the AER for specific SPCs after specific first cancers was highest for prostate cancer after first cancers of the urinary tract (AER, 54.3 per 10,000 person-years).Conclusions: In Tasmania, the risk of SPCs among survivors of adult-onset cancers has increased with periods of first cancer diagnosis from 1980 through 2009. Increased cancer screening and improved medical imaging may have contributed to the greater risk in recent years. Cancer 2018;124:1808-18. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

We aimed at investigating risk of specific second primary cancers (SPCs) after malignant mesothelioma (MM) and vice versa, which has not been reported. Among survivors of 3672 pleural MM and 895 peritoneal MM, overall 113 and 28 SPCs were recorded, respectively, while reverse analyses included overall 431 pleural and 88 peritoneal MMs after any first cancers. We found a bidirectional association of pleural MM with kidney cancer for overall [for second kidney cancer after pleural MM: standardized incidence ratios (SIRs) = 4.4, 95% confidence intervals (CIs): 2.0-8.3; for second pleural MM after kidney cancer: 2.3 (1.3-3.9)] and for <1 year follow-up [5.4 (2.0-12) and 4.9 (2.0-10), respectively, according to the 2-way analyses]. In contrast, a bidirectional association of pleural MM with unknown primary cancer was found only for follow-up ≥1 year [3.9 (1.1-10) and 2.8 (1.3-5.1), respectively]. We found a bidirectional association of pleural MM with kidney cancer for overall and for <1 year follow-up, suggesting the involvement of germline BAP1 mutations and increased medical surveillance, while the bidirectional association of pleural MM with unknown primary cancer suggests shared genetic or environmental risk factors. [ABSTRACT FROM AUTHOR]

Survivors of childhood cancer have a higher mortality than the general population. We describe cause-specific long-term mortality in a population-based cohort of childhood cancer survivors. We included all children diagnosed with cancer in Switzerland (1976-2007) at age 0-14 years, who survived ≥5 years after diagnosis and followed survivors until December 31, 2012. We obtained causes of death (COD) from the Swiss mortality statistics and used data from the Swiss general population to calculate age-, calendar year-, and sex-standardized mortality ratios (SMR), and absolute excess risks (AER) for different COD, by Poisson regression. We included 3,965 survivors and 49,704 person years at risk. Of these, 246 (6.2%) died, which was 11 times higher than expected (SMR 11.0). Mortality was particularly high for diseases of the respiratory (SMR 14.8) and circulatory system (SMR 12.7), and for second cancers (SMR 11.6). The pattern of cause-specific mortality differed by primary cancer diagnosis, and changed with time since diagnosis. In the first 10 years after 5-year survival, 78.9% of excess deaths were caused by recurrence of the original cancer (AER 46.1). Twenty-five years after diagnosis, only 36.5% (AER 9.1) were caused by recurrence, 21.3% by second cancers (AER 5.3) and 33.3% by circulatory diseases (AER 8.3). Our study confirms an elevated mortality in survivors of childhood cancer for at least 30 years after diagnosis with an increased proportion of deaths caused by late toxicities of the treatment. The results underline the importance of clinical follow-up continuing years after the end of treatment for childhood cancer. [ABSTRACT FROM AUTHOR]

The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67-1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen. [ABSTRACT FROM AUTHOR]