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PURPOSE: The effectiveness of current follow-up guidelines after breast cancer treatment is uncertain. Tailored surveillance based on patient age and tumor characteristics may be more adequate. This study aimed to analyze the frequency of ipsilateral locoregional recurrences (LR) and second primary breast cancers (SP) detected outside of scheduled surveillance and to analyze risk factors associated with these events. METHODS: Patients with surgically treated early-stage breast cancer from the Malmö Diet and Cancer Study (MDCS), 1991-2014 (n = 1080), and the Västernorrland region, 2009-2018 (n = 1648), were included. Clinical and pathological information on the primary tumor and recurrences was retrieved from medical records. The mode of recurrence detection was defined as detection within (planned) or outside (symptomatic) of scheduled surveillance. RESULTS: The median follow-up was 6.5 years. Overall, 461 patients experienced a recurrence. The most common initial event was distant metastasis (47%), followed by locoregional recurrence (LR) (22%) and second primary (SP) (18%). 56% of LR and 28% of SP were identified outside of scheduled surveillance. Logistic regression analysis revealed that younger age (under 50 years) (OR 2.57, 95% CI 1.04-6.88), lymph node-positive breast cancer (OR 2.10, 95% CI 1.03-4.39) and breast cancer of the HER2 positive subtype (OR 5.24, 95% CI 1.40-25.90) were correlated with higher odds of detecting a recurrence outside of planned surveillance. CONCLUSION: Most recurrent events were detected outside of scheduled surveillance, particularly for locoregional recurrences. Risk-based surveillance, which takes into account patient and tumor characteristics, might be more suitable for specific patient subsets.

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Background: With improving prognosis in upper-tract urothelial carcinoma (UTUC), an increasing number of second primary malignancies (SPMs) are being identified. However, there is limited research on SPMs following UTUC. This study aims to evaluate the risk of SPMs in UTUC patients and create a nomogram to predict their survival rates. Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, we assessed the risk of SPMs among UTUC patients. Additionally, we developed and validated an overall survival (OS) nomogram for SPM patients post-UTUC diagnosis. Results: The prevalence of SPMs among UTUC patients was 30.23%, with solid tumors being the most prevalent type of second malignancy, constituting 95.30% of all SPMs. The overall risk of SPMs was significantly elevated across all subgroups. Univariate and multivariate Cox regression analyses identified age, race, gender, UTUC SEER historic stage, surgery, SPM site, histologic type, grade, and SEER historic stage as independent prognostic factors for SPM OS. Subsequently, we developed a nomogram for predicting SPM OS. The C-index for the training and validation sets were 0.72 [95% confidence interval (CI): 0.70-0.74] and 0.71 (95% CI: 0.67-0.75), respectively. The area under the curve (AUC) demonstrated good performance of our model in predicting the 3-year (0.73 and 0.737) and 5-year (0.723 and 0.733) OS of SPMs in both sets. Conclusions: This study represents the first comprehensive analysis of SPM incidence in UTUC patients and introduces a nomogram for predicting SPM prognosis.

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The long survival of patients with primary cancer increases the chance of such patients developing second primary cancer (SPC). The development of SPC in cancer survivors exerts a large psychological, social and economic burden on patients and their families. The aim of the present study was to assess the risk of cancer survivors developing SPC. The study included patients who had been diagnosed with a first primary cancer in five organs (stomach, colorectum, lung, breast and thyroid), which are the five most common sites of cancer in patients from Korea, at the regional cancer center in Jeonbuk National University Hospital between January 2007 and December 2009. The standardized incidence ratio (SIR) of SPC according to sex and site was calculated from 5,209 patients who were followed up to September 2017. General incidence was acquired from the National Cancer Registry of Republic of Korea. SPC occurred in 6.2% (323/5,209) of patients, and the incidence of SPC among the five major types of cancer was in the order of breast (8.8%, 46/524), colorectum (8.6%, 86/1,003), gastric (6.6%, 89/1,358), thyroid (4.7%, 67/1,437) and lung cancer (3.9%, 35/887). When all SPC sites were included, the SIRs of SPC in patients with colorectal cancer and breast cancer were >1.0 (1.21 and 1.66, respectively). Breast cancer and thyroid cancer exhibited a high site relationship (P<0.05), and colorectal cancer had a high site relationship with gastric cancer (P<0.05). The present study analyzed the incidence and pattern of SPC in patients with cancer who were diagnosed with primary carcinoma in five organs. The results of the study may be useful for effective follow-up and early detection of SPC in patients with cancer.

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Purpose: The aim of this study was to analyze the survival of patients with endometrial cancer diagnosed after a prior cancer and identify risk factors of endometrial cancer death in this population. Methods: Totally 1371 women diagnosed with second primary endometrial cancer (SPEC) between 2004 and 2015 were identified using the SEER database. Clinicopathological characteristics were collected, and Fine and Gray regression model was employed to assess the impact of treatment for the first primary cancer (FPC) and SPEC on the mortality of endometrial cancer patients. After propensity score matching (PSM), patients diagnosed with single primary endometrial cancer and SPEC between 2004 and 2015 were included as the second cohort. Kaplan-Meier and Cox survival risk models were used to assess the influence of previous cancer history on survival. Results: Patients previously diagnosed as lung cancer exhibited the lowest overall survival (OS). A diagnostic interval of ≥3 years was significantly associated with higher mortality from SPEC compared with that <3 years. Surgical treatment for SPEC was linked to a reduced risk of endometrial cancer-specific mortality (ECSM) and non-ECSM. Conversely, radiotherapy and chemotherapy were associated with an increased risk of ECSM. The 1-, 3-, and 5-year OS rates of patients with SPEC were significantly lower than those with single primary endometrial cancer whether before or after PSM. Univariate and multivariate analyses further demonstrated that endometrial cancer, either as FPC or SPEC, was independently associated with an increased risk for endometrial cancer-specific survival (ECSS) and OS. Conclusion: Chemotherapy and radiotherapy for SPEC can elevate the risk of ECSM. Whether as FPC or SPEC, endometrial cancer is demonstrated to be a significant independent risk factor for ECSS and OS.

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Introduction: Organ dose distribution calculation in radiotherapy and knowledge about its side effects in cancer etiology is the most concern for medical physicists. Calculation of organ dose distribution for breast cancer treatment plans with Monte Carlo (MC) simulation is the main goal of this study. Materials and Methods: Elekta Precise linear accelerator (LINAC) photon mode was simulated and verified using the GEANT4 application for tomographic emission. Eight different radiotherapy treatment plans on RANDO's phantom left breast were produced with the ISOgray treatment planning system (TPS). The simulated plans verified photon dose distribution in clinical tumor volume (CTV) with TPS dose volume histogram (DVH) and gamma index tools. To verify photon dose distribution in out-of-field organs, the point dose measurement results were compared with the same point doses in the MC simulation. Eventually, the DVHs for out-of-field organs that were extracted from the TPS and MC simulation were compared. Results: Based on the implementation of gamma index tools with 2%/2 mm criteria, the simulated LINAC output demonstrated high agreement with the experimental measurements. Plan simulation for in-field and out-of-field organs had an acceptable agreement with TPS and experimental measurement, respectively. There was a difference between DVHs extracted from the TPS and MC simulation for out-of-field organs in low-dose parts. This difference is due to the inability of the TPS to calculate dose distribution in out-of-field organs. Conclusion and Discussion: Based on the results, it was concluded that the treatment plans with the MC simulation have a high accuracy for the calculation of out-of-field dose distribution and could play a significant role in evaluating the important role of dose distribution for second primary cancer estimation.

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A significant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.7-1%) of the development of second primary cancers compared to patients treated with surgery up to 25 years after treatment. However, current evidence suggests that the implementation of intensity modulated radiation therapy is not increasing the risk of second primary cancers compared to conformal 3D-planned radiotherapy. Furthermore, increasing evidence indicates that highly conformal radiotherapy techniques may not increase the probability of second primary cancers compared to radical prostatectomy. Consequently, future studies should consider the radiotherapy technique and other confounding factors to provide a more accurate estimation of the occurrence of second primary cancers.

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Background: No data is available on hypomineralization in the full complement of primary dentition. Aim: To report on the prevalence and clinical presentation of enamel hypomineralization (EH) in the primary dentition. Design: A cross-sectional observational study with a random sample of 948, 4-6-year-old schoolchildren of Gautam Buddh Nagar, Uttar Pradesh, India, was conducted after approval from the Institutional Ethics Committee. European Academy of Paediatric Dentistry (EAPD) (2003) criteria were employed to score EH in all primary teeth. A single experienced examiner conducted an entire clinical examination of the study population. Data were expressed as the prevalence, type, extent, and distribution. Further analyses were conducted to compare the prevalence and distribution of different types of lesions in affected subjects using student t-tests and analysis of variance (ANOVA). Results: An overall prevalence of 7.51% (71/948) was reported. A total of 2.75 ± 1.735 teeth/subject were reported to be affected. The most common lesion was creamy white opacity (p = 0.002), while posteruptive breakdown (PEB) was observed in 40.85% (29/71) of affected subjects. Conclusion: The prevalence of EH in primary dentition was 7.51%. Further studies mapping the prevalence as well as possible links with molar incisor hypomineralization (MIH) in other geographical locations of the world are required. How to cite this article: Mittal N, Gupta N, Goyal A. Enamel Hypomineralization: Prevalence, Defect Characteristics in Primary Dentition in a Northern Indian Region. Int J Clin Pediatr Dent 2024;17(S-1):S67-S72.

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Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissection (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retrospectively included early ESCN patients treated with ESD at two medical centers in Taiwan between August 2010 and December 2023. Demographic, endoscopic and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resections were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resections were significantly associated with recurrence in a univariate analysis (HR: 0.19, 95% CI: 0.06-0.66, p = 0.008). Alcohol abstinence was independently associated with lower recurrence (HR: 0.34, 95% CI: 0.16-0.73, p = 0.006). Patients with pT1a-MM (muscularis mucosa invasion) had comparable OS (p = 0.82), DSS (p = 0.617) and recurrence (p = 0.63) rates to those with pT1a-EP/LPM (epithelium/lamina propria invasion). The long-term outcomes of ESCN patients after ESD for expanded indications were satisfactory. ESD could be considered in selected ESCN patients involving the muscularis mucosa, notably among high-risk HNC patients.

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Key Clinical Message: Epithelial-myoepithelial carcinoma of the breast is an extremely rare biphasic tumor. This report documents the first case of epithelial-myoepithelial carcinoma presenting in the location of a previously treated ductal carcinoma in order to increase the awareness of this entity as a potential differential for recurrent breast lesions. Abstract: Epithelial-myoepithelial carcinoma of the breast is an exceedingly rare biphasic tumor, seldom documented in medical literature. This report describes the first known case of this entity at the site of a previously treated neoplasm in a 75-year-old female with a history of high-grade ductal carcinoma in situ who presented with a new breast mass. Imaging demonstrated an oval shaped mass with microlobulated borders and hypoechoic echogenicity on ultrasound. Following multidisciplinary discussion, she underwent a mastectomy, revealing epithelial-myoepithelial carcinoma with metaplastic squamous cell carcinoma. The patient began chemotherapy but discontinued due to poor tolerance and neurological complications. Generally, prognosis for epithelial-myoepithelial carcinoma (World Health Organization Classification of Breast Tumors 2019, 8562/3) is highly variable, with limited available data suggesting that epithelial-myoepithelial carcinoma may follow a course similar to that of breast adenocarcinomas with both hematogenous and lymphatic spread. Treatment typically involves curative excision, though the role of axillary lymph node sampling remains under discussion. This case underscores the need for vigilance in post-treatment surveillance for breast cancer and highlights the importance of recognizing this entity in recurrent breast pathology.

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The occurrence of second primary malignancies is becoming increasingly important among cancer survivors. Melanoma, an aggressive neoplasm originating from the melanocytes, is responsible for most skin cancer-related deaths. This review aims to explore the risk of melanoma occurrence as a second primary cancer after the most common subtypes of hematologic neoplasia, a malignant disease originating from myeloid or lymphocytic cell lineages. Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are among the most associated subtypes with melanoma development. We also discuss the underlying hypotheses that may explain the associations between these malignancies and the impact of melanoma on survival. The review emphasizes the importance of increasing awareness of melanoma risk in hematologic cancer survivors, as it can lead to prompt recognition, improved skin surveillance, and better survival outcomes.

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Background: After improvement in the treatment of oral cancers over the years we now see more patients with recurrent oral squamous cell carcinoma (OSCC) and second primary. Recommendations for addressing the neck (ipsilateral and/or contralateral) in these patients are still unclear and debatable. Methods: In this retrospective study we included patients with recurrent and second primary OSCC who underwent surgery between January 2016 and December 2021. We analysed to identify factors and better imaging modality that help predict a pathologically N + neck in these patients. Results: In our cohort of 219 patients treated for recurrent/second primary OSCC, 131 patients underwent a neck dissection along with surgery for primary, out of which 59 patients had pN + neck. Factors that predicted ipsilateral pN + status were the clinical stage (advanced) p = 0.009, 2.724(1.291-5.750), subsite (Tongue + floor of mouth) p = 0.01, 3.105(1.305-7.386), previous treatment received (surgery alone) p = 0.0472.148(1.011-4.562) and histopathology [poorly differentiated squamous cell carcinoma (PDSCC)] p = 0.014, 3.070(1.253-7.519). PET-CECT had the best agreement (p < 0.001, kappa = 0.742) to predict nodal metastasis. There were no factors that could predict contralateral nodal metastasis. Conclusions: Patients with advanced clinical stage, Tongue + floor of mouth subsite, only surgery done previously, and histopathology (PDSCC) had a higher incidence of ipsilateral nodal metastasis in our cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-024-02272-8.

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OBJECTIVE: Prevention of subsequent primary cancer (SPC) is crucial for cancer survivors, particularly those who developed the disease during childhood, adolescence, and young adulthood (CAYA). The aim of this study was to assess the current status of SPC prevention among female CAYA cancer survivors. METHODS: A survey regarding long-term health issues after cancer treatment was conducted using questionnaires that targeted women aged ≥20 years who had developed cancer before the age of 40 years. The survey assessed various health issues, and this paper focuses on the items related to the respondents' perceptions and attitudes toward SPC prevention. RESULTS: A total of 1,026 respondents were analyzed. Over 60% of respondents were aware of SPC and the need for screening. The percentages of respondents who underwent regular SPC screening were 68.3%, 68.4%, 49.7%, 58.6%, and 57.0% for cervical, breast, lung, and gastric cancers, respectively. After adjusting for age, type of first cancer, and current follow-up, we found that receiving recommendations for SPC screening was the most critical factor in SPC screening uptake (odds ratio=3.836; 95% confidence interval=2.281-6.451; p<0.001 by logistic regression analysis). However, only 40.4% of the respondents received recommendations for SPC screening from their physicians. CONCLUSION: Despite good awareness of SPC prevention, the uptake rate for cancer screening among cancer survivors was inadequate, indicating that preventive measures for SPC should be promoted. Because recommendations from others strongly influence SPC screening uptake, healthcare professionals should have accurate knowledge and provide guidance regarding SPC prevention.

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OBJECTIVE: The purpose of this study was to investigate the association between depressive symptoms and second primary cancer (SPC) in U.S. cancer survivors. METHODS: Cancer survivors from the 2005-2018 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study, and depressive symptoms were defined by the Patient Health Questionnaire 9 (PHQ-9). The association between depressive symptoms and SPC was assessed via multiple logistic regression, restricted cubic spline (RCS), sensitivity, and subgroup analyses. RESULTS: This study involved 2315 participants representing >15 million noninstitutionalized U.S. residents. Multivariate logistic regression fully adjusted for confounders revealed that cancer survivors with a PHQ-9 score ≥ 10 had a greater risk of developing SPC than those with a PHQ-9 score of 0-4 ([OR] = 1.88, 95% [CI] = 1.20-2.89, p = 0.005). The RCS showed a linear positive correlation between the PHQ-9 score and SPC (p for overall = 0.017). The robustness of this association was subsequently confirmed via multiple interpolation of missing data and different cluster-level methods (namely weighted linear regression) as sensitivity analyses. Furthermore, subgroup analyses confirmed this correlation was stronger in participants with sleep duration <7 h (p for interaction = 0.036). CONCLUSION: Moderate to severe depressive symptoms in cancer survivors were associated with an increased risk of developing SPC, especially at <7 h of sleep.

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INTRODUCTION: There is a correlation between molar incisor hypomineralization (MIH) and hypomineralized second primary molars (HSPM), but this relationship has not been definitively confirmed. The purpose of this systematic review and meta-analysis was to reevaluate whether children with HSPM are more affected by MIH than non-HSPM children. METHODS: A systematic search was conducted in four databases (PubMed, Embase, Web of Science, and the Cochrane Library) for literature, published up to December 2022. Two independent reviewers conducted the study search and screening, quality assessment, and data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The risk-of-bias assessment of all included cohort studies and case-control studies was assessed by the Newcastle-Ottawa Scale (NOS), and cross-sectional studies were assessed using the Agency for Healthcare Research Quality (AHRQ) scale. RevMan 5.4 software was used for all data analyses, with odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures. Sensitivity and subgroup analyses were conducted to identify the potential sources of heterogeneity among the studies. Publication bias was tested and corrected by funnel plots and Egger's test. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software to control for type-1 and type-2 errors. RESULTS: A total of 12 studies involving 8,944 children were included in this meta-analysis. Compared with the non-HSPM group, the HSPM group had an increased likelihood of MIH (OR = 10.90, 95% CI = 4.59-25.89, p < 0.05). All the included studies were of moderate-to-high quality. TSA and sensitivity analyses suggested the robustness of this outcome. CONCLUSION: This systematic review demonstrated a certain correlation between HSPM and MIH, suggesting that HSPM can play a predictive role in the occurrence of MIH. Further high-quality, multicenter, and large-sample longitudinal studies are highly recommended.

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To examine the potential correlation between chemotherapy and the risk of individual of second primary endometrial cancer (SEC) in patients with rectal cancer (RC) and assess survival outcomes. The study employed the Surveillance, Epidemiology, and End Results database (SEER) as the primary data source, it encompasses a substantial cohort of patients diagnosed with RC between 1975 and 2018. This study involved a total of 30,847 individuals diagnosed with RC, of whom 168 individuals (5.45‰) experienced SEC. Among them, 107 patients (3.47‰) received chemotherapy treatment, while 61 patients (1.98‰) did not receive chemotherapy. The analysis of the overall occurrence of SEC revealed a significant association between SEC and chemotherapy treatment. Univariate and multivariate analyses confirmed a significant association between chemotherapy treatment and an increased risk of developing SEC in RC patients. Upon implementation of a dynamic analysis on the variables of relative risk and standardized incidence ratios, the results revealed that the likelihood of SEC escalated in tandem with advancing age. The examination of patients who developed SEC after receiving and not receiving chemotherapy revealed no substantial disparities in the 10-year overall survival (OS) and (cancer-specific survival) CSS rates. The results were the same after propensity score matching. Nevertheless, a notable discrepancy emerged when comparing the OS and CSS rates at 10 years between patients afflicted with SEC subsequent to chemotherapy and those afflicted with primary endometrial cancer, and the result was the same situation in the no-chemotherapy group. The use of chemotherapy in RC patients has been associated with an increased probability of developing specific SEC. Therefore, it is imperative to prioritize efforts aimed at reducing chemotherapy-related SEC occurrences and improving the prognosis of affected individuals.

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Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000-2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy's impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06-1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.

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This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan-Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146-4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291-4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028-3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006-2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193-4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

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As a result of an increased focus on early detection including lung cancer screening, combined with more curative treatment options, the 5-year survival rates for lung cancer are improving. Welcome though this is, it brings new, hitherto unseen challenges. As more patients are cured and survive longer, they are at risk of developing second primary cancers, particularly lung cancer. In this review, we examine the challenges that surveillance, diagnosis, and management of second primary lung cancer (SPLC) bring and how these can be addressed. Recent data from prospective follow-up studies suggests that the incidence of SPLC may be higher than previously appreciated, partly due to an increase in multi-focal adenocarcinoma spectrum disease. Over 5 years, up to 1 in 6 long-term lung cancer survivors may develop a SPLC. Although not routinely used in clinical practice at present, genomic approaches for differentiating SPLC from intrapulmonary metastases of the first primary are emerging, and we highlight how this could be used to help differentiate lesions. An accurate distinction between SPLC and the recurrence of the first primary is of paramount importance due to the very different management strategies that may be required. Wrongly classifying an SPLC as a recurrence of the first primary may have significant consequences for patient management and overall survival. Updated approaches to the classification of SPLC combining clinical history, histopathological assessment, and genomic profiling are needed. Finally, we review the potential role of early detection biomarkers in the identification of SPLC, focusing in particular on blood-based biomarkers that are being examined in a multi-center prospective study recruiting lung cancer survivors.

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BACKGROUND: Studies have found that first primary cancer (FPC) survivors are at high risk of developing second primary breast cancer (SPBC). However, there is a lack of prognostic studies specifically focusing on patients with SPBC. METHODS: This retrospective study used data from Surveillance, Epidemiology and End Results Program. We selected female FPC survivors diagnosed with SPBC from 12 registries (from January 1998 to December 2018) to construct prognostic models. Meanwhile, SPBC patients selected from another five registries (from January 2010 to December 2018) were used as the validation set to test the model's generalization ability. Four machine learning models and a Cox proportional hazards regression (CoxPH) were constructed to predict the overall survival of SPBC patients. Univariate and multivariate Cox regression analyses were used for feature selection. Model performance was assessed using time-dependent area under the ROC curve (t-AUC) and integrated Brier score (iBrier). RESULTS: A total of 10,321 female FPC survivors with SPBC (mean age [SD]: 66.03 [11.17]) were included for model construction. These patients were randomly split into a training set (mean age [SD]: 65.98 [11.15]) and a test set (mean age [SD]: 66.15 [11.23]) with a ratio of 7:3. In validation set, a total of 3,638 SPBC patients (mean age [SD]: 66.28 [10.68]) were finally enrolled. Sixteen features were selected for model construction through univariate and multivariable Cox regression analyses. Among five models, random survival forest model showed excellent performance with a t-AUC of 0.805 (95 %CI: 0.803 - 0.807) and an iBrier of 0.123 (95 %CI: 0.122 - 0.124) on testing set, as well as a t-AUC of 0.803 (95 %CI: 0.801 - 0.807) and an iBrier of 0.098 (95 %CI: 0.096 - 0.103) on validation set. Through feature importance ranking, the top one and other top five key predictive features of the random survival forest model were identified, namely age, stage, regional nodes positive, latency, radiotherapy, and surgery. CONCLUSIONS: The random survival forest model outperformed CoxPH and other machine learning models in predicting the overall survival of patients with SPBC, which was helpful for the monitoring of high-risk populations.

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