Second Primary Cancer Research Articles

The effect of thyroid cancer on the survival of patients with digestive system tumors using SEER database.

The number of cancer survivors worldwide is increasing every year, making secondary primary cancers (SPC) is a growing health threat. Studies have been conducted to investigate the risk of occurrence between digestive system tumors (DST) and thyroid cancer (TC). However, existing studies have tended to focus more on the risk of developing SPC and less on the impact of SPC on the survival of cancer survivors. In this study, using the Surveillance, Epidemiology, and End Results database, we aimed to explore the impact of TC on the survival of patients with DST by data between 2000 and 2018. The study employed the standardized incidence ratio to assess the relative risk of SPC, propensity score matching was conducted to mitigate confounding effects, Kaplan-Meier, Cox proportional risk model and competitive risk model were used to analyze the factors affecting the overall survival and cancer-specific survival. We furthermore explored the influence of pathological types and radiotherapy of TC on the survival of DST patients. 518,901 patients with DST only, 801 patients with TC occurring earlier than DST (TC-1st), and 744 patients with DST occurring earlier than TC (DST-1st) were included. The total incidence rate of small intestine cancer after TC was higher than that of the general population, and the incidence of TC after DST was higher than in the general population. DST patients with a history of TC had better overall survival and lower cancer-specific mortality and this difference was particularly significant in patients with DST-1st. In addition, radiotherapy for TC had no effect on cancer-specific mortality in patients with DST.

Second primary cancers in patients with a pharyngeal index tumour: a register-based cohort study.

While prior research on the SPC (second primary cancer) risk among pharyngeal carcinoma (PC) patients has been conducted in other regions, the European perspective is underrepresented. Our register-based cohort study aims to assess the subsite-specific risk of SPC among individuals initially diagnosed with a pharyngeal index tumour. Standardized incidence ratios (SIR) of SPC were calculated relative to the general population for all patients diagnosed with a primary oropharyngeal, nasopharyngeal, and hypopharyngeal carcinoma (OPC, NPC, and HPC) in Finland during 1953-2021. A total of 4701 PC patients - 3320 men (71%) and 1381 women (29%) - were identified. The average and median follow-up times were 5.7 and 2.8 years, respectively. A SPC was diagnosed in 561 patients (11.9%): in 12.3% of men (n = 410) and 10.9% of women (n = 151). For male PC patients, the overall SIR for an SPC at any primary site was 1.83 (95% CI: 1.65-2.01). For female patients, the corresponding SIR was 1.89 (95% CI: 1.60-2.22). OPC and HPC showed increased risks for SPCs of the mouth/pharynx (SIR 4.41 and 6.91, respectively) and respiratory organs (SIR 3.51 and 4.80). OPC patients also had an increased risk in digestive organs (SIR 1.83). Male NPC patients exhibited increased risks for oral/pharyngeal, brain, and haematolymphoid SPCs (SIRs 5.14, 6.60, and 3.05, respectively). PC patients face an 80% higher SPC risk, which persists decades after treatment. Healthcare professionals must be aware of this, providing counselling and encouraging a healthy lifestyle, including smoking cessation, while monitoring symptoms.

The association between breast cancer and lung cancer: a bidirectional Mendelian randomization study.

With increasing life spans, breast cancer (BC) survivors may face the possibility of developing second primary cancer (SPC), which can considerably shorten survival. Lung cancer (LC) is a common SPC among BC survivors. This study explored the association between these two cancers through Mendelian randomization (MR) analysis. A bidirectional two-sample MR analysis was conducted with BC genome-wide association study (GWAS) data from the Breast Cancer Association Consortium (BCAC) included 228,951 individuals and the GWAS summary statistics from the Transdisciplinary Research in Cancer of the Lung (TRICL) of LC included 112,781 individuals. The IVW method and MR-RAPS method showed a causal effect of overall BC on lung adenocarcinoma (LUAD) (IVW: OR = 1.060, 95% CI = 1.008-1.116, P = 0.024; MR-RAPS: OR = 1.059, 95% CI = 1.005-1.116, P = 0.033), which indicated that patients with BC had an increased risk of LUAD. However, there is no strong evidence for a causal effect of LUAD on BC. Our study revealed a causal effect of BC on second primary LUAD, suggesting that we should intensify screening for second primary LC in BC survivors. Early intervention and treatment for patients with second primary LC are needed to reduce mortality in BC survivors.

Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers.

Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records. We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks. There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% (BRCA1 carriers), 12%/3.0%/6.2% (BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers. Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

The risk and distribution of second primary cancers according to subsite of primary stomach cancer: a retrospective cohort population-based study

Background: The development of second primary cancers (SPCs) following a diagnosis of stomach cancer presents a significant clinical challenge, with varying risks depending on the anatomic subsite of the primary tumor, patient demographics, and treatment modalities. This study aims to assess the risk of SPCs in stomach cancer survivors, focusing on differences across anatomic subsites, gender, age, and treatment periods. Methods: We conducted a retrospective cohort study using data from stomach cancer patients, analyzing the incidence of SPCs based on the anatomic location of the primary tumor, with stratifications by gender, age, latency period, and year of diagnosis. Standardized incidence ratios (SIRs) were calculated to compare the observed SPC rates with those expected in the general population. Results: Elevated stomach SPC risk was observed across most anatomic subsites, particularly in the body (SIR 8.84) and fundus (SIR 7.34). Females exhibited higher SIRs compared to males, especially in the fundus (SIR 13.33 for females vs. 4.55 for males). Younger patients (<50 years) had significantly higher SPC risks, particularly for cancers originating in the fundus (SIR 49.56). Notably, patients diagnosed after 2010 showed the highest SIRs, indicating a potential impact of advances in diagnostic and therapeutic modalities. Non-stomach SPCs, including colorectal, lung, and thyroid cancers, were significantly elevated, with distinct patterns based on the primary tumor site. Conclusions: The study highlights the critical role of primary tumor location, gender, age, and treatment era in determining SPC risk in stomach cancer survivors. These findings underscore the need for tailored surveillance strategies to manage long-term cancer risks in this population.

HLA diversity unveils susceptibility and organ-specific occurrence of second primary cancers: a prospective cohort study

BackgroundUp to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence.MethodsWe analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles.ResultsDuring a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59–0.89; females: HR 0.81, 95% CI 0.70–0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03–1.56; females: HR 1.35, 95% CI 1.07–1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females.ConclusionsThese results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.

Empowering survivors, elevating care: The vital role of oncology primary care clinics.

362 Background: Due to increasing numbers of cancer survivors, there is a greater focus on the longitudinal management of treatment-related comorbidities. Cancer survivors have increased risk of cardiovascular (CV) disease, CV-related mortality, and second primary cancers (SPCs). Primary care providers (PCPs) are responsible for most of the care of long-term survivors, however, many report uncertainty around long-term effects and survivorship guidelines. While fostering strong primary care-oncology relationships is one approach to support those impacted by cancer, the development of oncology primary care clinics enhances patient outcomes and ensures patients receive comprehensive survivorship care. Despite this, few tertiary cancer care centers offer such clinics. Methods: In 2021, the University of Cincinnati Cancer Center established an oncology primary care clinic. Patients are eligible if they have a current or prior cancer diagnosis or cancer hereditary syndrome (CHS). The clinic is comprised of two-family medicine physicians, one with survivorship experience, and one fellowship-trained in palliative and hospice medicine. Clinical team members include an RN with oncology experience, medical assistants, a clinical service specialist, two oncology clinical pharmacists, and an oncology social worker. A clinical registry was developed to longitudinally measure patient outcomes. Electronic medical records of patients (n=683) seen between 1/2021 and 1/2024 were extracted and entered in REDCap. Data was summarized using SAS. Results: The mean age was 56 years (range 20-93), and 12% received a diagnosis in the pediatric/adolescent/young adult age range (0-39 years). The most common types included breast (23%),hematologic cancers (15%), and CHS (16%). Notably 43% of patients are on active treatment and 53% completed or are on maintenance treatment. Over 61% struggle with obesity, while 45% report being a current or former smoker. Comorbidities were common with 79% of patients having at least one CV diagnosis. Of 57% patients eligible for cardiomyopathy screening, 78% received recommended echocardiograms. Many patients received their recommended screenings including breast (79%), colon (43%), cervical (56%), prostate (46%), and lung (55%). Patients were referred to a variety of supportive services including physical therapy (42%), cancer exercise (18%) and psychiatry (14%). Conclusions: This model of care is a viable option for connecting cancer survivors with PCPs knowledgeable about survivorship care. CV-related comorbidities were common, and their management is a critical need during and after cancer. Survivors have increased risk of SPCs, and while the number of patients up to date on recommended cancer screenings is low, screenings are on the rise with ongoing efforts. Patient registries enable objective measurement of outcomes and can inform future research and care.

Metachronous Second Primary in the Form of Nasopharyngeal Carcinoma Following Treatment of Small Cell Neuroendocrine Carcinoma of the Head and Neck: Dual Tracer PET/CT Findings Highlighting SSTR2 Expression and Its Theranostic Implications

AbstractPatients of head and neck squamous cell carcinoma (HNSCC) experience increased risk of developing second primary cancer (SPC) necessitating active surveillance during their disease course. SPCs are associated with poor prognosis and are the leading cause of long-term morbidity and mortality impacting survival of patients with HNSCC. Small cell neuroendocrine carcinoma (SmNEC) is a rare but aggressive neoplasm with poor prognosis and high risk of local recurrence and distant metastasis. We report an exceedingly rare case of nasopharyngeal carcinoma (NPC) presenting as a recurrence in the form of metachronous second primary to primary SmNEC 9 years after chemotherapy. The dual tracer positron emission tomography and computed tomography (PET/CT) imaging approach ([68Ga]Ga-DOTATATE-PET/CT with 18F-FDG-PET/CT) was explored in such metachronous NPCs, and the findings are illustrated with its potential for theranostic applications. NPC is a rare malignancy with significant geographical variations in incidence rates. Somatostatin receptor 2 (SSTR2) expression in NPC is well documented and can serve as a potential theragnostic marker in advanced NPC where the successful outcome is minimal with currently available treatment modalities.

Incidence and pattern of second primary cancer in patients diagnosed with primary cancer.

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.

Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy

PurposePrevious studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and MethodsUsing the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). ResultsIn total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. ConclusionIn this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

Association between depressive symptoms and second primary cancer in cancer survivors: Insights from a nationally representative study

ObjectiveThe purpose of this study was to investigate the association between depressive symptoms and second primary cancer (SPC) in U.S. cancer survivors. MethodsCancer 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. ResultsThis 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). ConclusionModerate to severe depressive symptoms in cancer survivors were associated with an increased risk of developing SPC, especially at <7 h of sleep.

Longitudinal Risk Analysis of Second Primary Cancer after Curative Treatment in Patients with Rectal Cancer.

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.

Risk of Second Primary Cancer Among Patients with Cardio-Esophageal Cancer in Finland: A Nationwide Population-Based Study.

The occurrence of a second primary cancer (SPC) after primary esophageal carcinoma (EC) or gastric cardia carcinoma(GCC) is well acknowledged. However, previous research on the risk of SPC among these patients has been predominantly conducted in Asian countries. Yet, notable population-dependent variation in histological types and risk profiles exists. This register-based study assesses the histology-specific risk of SPC among individuals initially diagnosed with a first primary EC or GCC. We obtained data on 7197 patients diagnosed with EC/GCC in Finland between 1980 and 2022 from the Finnish Cancer Registry. Standardized incidence ratios (SIR) of SPC were subsequently calculated relatively to the cancer risk of the general population. The average and median follow-up times were 2.8 years and 10.5 months. Adenocarcinomas and squamous cell carcinomas comprised 57.8% (n = 4165) and 36.6% (n = 2631) of all cases, respectively. An increased SIR was noted among EC/GCC patients after 15-20 years of follow-up (SIR 1.49, 95% CI: 1.01-2.11). Among adenocarcinoma patients, an increased SIR for SPCs of the digestive organs was seen in the 40-54-year-old group (SIR 9.86, 95% CI: 3.62-21.45). Squamous cell carcinoma patients displayed increased SIRs for cancer of the mouth/pharynx (SIR 3.20, 95% CI: 1.17-6.95) and respiratory organs (1.77, 1.07-2.76). Healthcare professionals should be aware of the increased risk of SPCs occurring in the mouth/pharynx, respiratory and digestive organs in survivors of EC/GCC. Patients should be advised about this risk and remain alert for symptoms, even beyond the standard 5-year follow-up period.

The impact of baseline health factors on second primary cancer risk after radiotherapy for prostate cancer.

In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.

Risk Factors for Second Primary Cancer in a Prospective Cohort of Endometrial Cancer Survivors: an Alberta Endometrial Cancer Cohort Study.

We examined associations between modifiable and non-modifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years post-diagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray sub-distribution hazard models. During a median follow-up of 16.7 years (interquartile range (IQR)=12.2-17.9), 89 (17%) participants developed a SPC with breast (29%), colorectal (13%) and lung (12%) cancers being the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs. <90.4 g/day: sub-hazard ratios (sHR)=1.71, 95% confidence intervals (CI)=1.09-2.69) as well as older age (≥60 vs. <60: sHR=2.48, 95% CI=1.34-4.62) and alcohol intake (≥2 drink/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 one-in-six survivors developing a 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.

Clinical Significance of Human Papillomavirus DNA Test and p16 Overexpression in Oropharyngeal Cancer

Background and Objectives Oropharyngeal squamous cell carcinoma (OPSCC) can be caused by human papilloma virus (HPV) infection or other factors like smoking. The 8th Edition of the AJCC Cancer Staging Manual recommends different staging and treatment approaches based on etiology. Despite criticisms of its low specificity, the current guidelines suggest using p16 immunohistochemistry (IHC) as a surrogate marker for the HPV-related OPSCC. This study assessed the reliability of p16 as a surrogate marker by correlating the survival rates of OPSCC patients with the results of p16 IHC and HPV-DNA testing.Subjects and Method A retrospective analysis was performed on patients treated for tonsil squamous cell carcinoma at a tertiary medical institution between 1994 and 2018. All patients underwent p16 immunostaining and HPV-DNA chip tests. Out of 88 patients, 17 were excluded due to insufficient data or secondary primary cancer, leaving 71 patients.Results Among the 71 patients, 51 were p16 positive and 49 were HPV-DNA positive; both tests were associated with extended survival. However, discrepancies were noted in 18 patients: specifically, 11 patients were p16 positive but HPV-DNA negative, displaying a different survival pattern compared to HPV-associated and non-HPV-associated patients.Conclusion Both p16 immunostaining and HPV-DNA testing have their pros and cons. p16 immunostaining is cost-effective but has lower specificity. The study found discrepancies in 18 patients, suggesting that relying solely on p16 immunostaining may have limitations. It would be advisable to complement it with additional tests like the HPV-DNA chip test to predict the disease’s prognosis more accurately.

Ten-Year Follow-Up of Lung Cancer Patients with Resected Stage IA Invasive Non-Small Cell Lung Cancer.

The purpose of this study was to assess 10-year follow-up outcomes after surgical resection in patients with stage IA invasive non-small cell lung cancer (NSCLC) based on postoperative pathological diagnosis. Patients with stage IA invasive NSCLC who underwent resection between December 2008 and December 2013 were reviewed. Patients were categorized into the pure-ground glass opacity (pGGO), mixed-ground glass opacity (mGGO), and solid groups based on consolidation to tumor ratio (CTR). Postoperative survival and risk of recurrence and developing secondary primary lung cancer were analyzed in each group. Among the 645 stage IA invasive NSCLC, the 10-year overall survival and recurrence-free survival rate was 79.38% and 77.44%, respectively. The 10-year overall survival for pGGO, mGGO, and solid group of patients was 95.08%, 86.21%, and 72.39%, respectively. The respective recurrence-free survival rate was 100%, 89.82%, and 65.83%. Multivariable Cox regression analysis associated tumor size and GGO components with recurrence and younger age, and tumors with GGO components were associated with longer overall survival. The cumulative incidence curve indicated no recurrence of GGO lung cancer ≥ 5 years postoperatively. Our cohort indicated that the number and stations of dissected lymph node did not influence long-term prognosis of IA invasive NSCLC. Recurrence of invasive stage IA NSCLC with GGO was more prevalent in patients with tumor size >1cm and CTR > 0.5, occurring within 5 years after surgery. This will provide important evidence for follow-up strategies in these patients.

The contribution of rare and common genetic variants to risk of prostate cancer and second primary cancer after prostate in the UK Biobank.

10604 Background: It has been estimated that up to 40% of prostate cancer may be attributed to inherited genetic susceptibility, yet very few variants have been consistently associated with risk and/or adverse outcomes after diagnosis. Moreover, because prostate cancer survival is generally good, risk of developing a second primary cancer (SPC) is an important concern. Identifying men at greater genetic risk of developing an SPC will lead to improved post-diagnostic cancer surveillance practices and lifestyle behavior modifications. Methods: The current investigation leverages genetic and phenotypical data from the UK Biobank (UKB) to examine inherited genetic factors, including rare pathogenic mutations (RPMs) and polygenic risk scores (PRS) with prostate cancer risk and SPC. The individual and joint contribution of (RPM in 26 cancer susceptibility genes and trans-ethnic PRS previously derived for 11 different cancer sites with both risk of prostate cancer and also SPCs among men diagnosed after primary prostate cancer. Cox regression models were used to estimate Hazard Ratio (HR) for prostate cancer, adjusted for age and ancestry. Cumulative incidence of SPC by person-year among prostate cancer patients was estimated from the age of diagnosis and compared with that in men without cancer. Results: Among 228,472 men in the UKB, 17,547 were diagnosed with prostate cancer. RPMs in five genes ( ATM, BRCA2, CHEK2, HOXB13 and PTEN) were significantly associated with prostate cancer risk. The rate of prostate cancer among RPM carriers was 15.59% compared with 7.72% in non-carriers (HR=2.26, 95% CI=1.97-2.59). The top decile of PRSProstate was associated with a 9.99-fold increase in risk of prostate cancer (95% CI=9.08-11). Having a diagnosis of prostate cancer had a significantly increased risk for two SPCs (bladder and kidney) and reduced risk for lung cancer, p&lt;0.001. Those that developed SPC of bladder cancer had significantly higher PRSBladder, p=5.91E-06. The number of RPM carriers (n=77) among SPC bladder cancers was prohibitively small to precisely estimate risk. Conclusions: In this large population-based cohort, both RPMs in largely DNA damage repair genes and PRS contribute to risk of prostate cancer and PRS with second primary bladder cancer among men with prostate cancer. These data both contribute to our understanding of the genetic susceptibility to prostate cancer and reinforce the need for refinement of genetic screening panels.

Beyond the initial diagnosis: Epidemiological factors associated with second primary cancers among patients with head and neck squamous cell carcinoma (a SEER-based study).

6081 Background: Patients with Head and Neck cancer squamous cell carcinoma (HNSSC) have an increased risk of developing a Second Primary Cancer (SPC). We evaluated the epidemiological factors associated with SPC among patients with Stage 1-4 HNSCC using the SEER database from 2004-2020. Methods: Stage 1-4 HNSSC cases from 2004-2020, with a minimum of six months of follow-up, were identified using SEER.Stat 8.4.2 using ICD-10 CM codes. Adjusted odd’s ratios (aOR) for developing SPC (dependent variable) and the independent variables (sex, age, race and ethnicity, site of primary cancer, and marital status) were generated using multivariate logistic regression. All the analyses were performed on SAS OnDemand. Results: 127,919 cases of HNSCC were identified from 2004-2020. Oral cavity cancer accounted for 41.2% of the cases. 18,192 (14.2%) patients developed SPC. Patients with primary hypopharynx, laryngeal, and oral cavity cancer had the highest odds of developing SPC (p&lt; 0.0001). The most prevalent sites for developing SPC were the lung (25.0%), head and neck (24.1%), and prostate (10.6 %). Males had significantly higher odds of developing SPC than females (aOR - 1.11 (1.07, 1.5)). When compared to the NH-white population, Hispanics and NH-Asian had significantly lower odds of developing SPC (aOR - 0.72 (0.68, 0.77) and 0.72 (0.68, 0.78) respectively), while NH-Blacks had higher odds of developing SPC (aOR - 1.1(1.01,1.23)). Conclusions: Our study emphasizes the substantial risk of SPC in HNSCC patients, with oral cavity cancer as the predominant primary cancer subtype. Specific HNSCC sites show elevated SPC odds, mainly primary hypopharyngeal cancer, emphasizing the need for targeted surveillance. Demographic variations reveal gender and racial disparities in SPC susceptibility, advocating for tailored monitoring and preventive strategies in high-risk subpopulations to enhance overall cancer care and survivorship. [Table: see text]

Synchronous Primary Head and Neck Tumors: Follicular Thyroid Carcinoma and Squamous Cell Carcinoma of The Tonsil

Simultaneously occurring malignancies may be detected in different organs or tissues at any given time. Patients diagnosed with a tumor may be found to have another tumor or second primary cancer. Second primary cancers (SPCs) may be further classified as synchronous or metachronous. Synchronous SPCs are lesions detected simultaneously or within 6 months after the diagnosis of the primary tumor while metachronous SPCs are tumors diagnosed 6 months after primary tumor diagnosis.1 There is an increased risk of having second primary cancer in Head and Neck Squamous Cell Carcinoma (HNSCC) patients.1 In a study by Strojan et al. in 2013, among 2,106 head and neck cancer patients, 2.4% developed synchronous second primary cancers.2 A systematic review by Coco-Pelaz et al. in 2020, showed that second primary tumors most frequently occur in the head and neck area followed by the lungs and esophagus.3 We present a case of follicular thyroid carcinoma with an incidental finding of cervical lymph node metastatic squamous cell carcinoma from the tonsil and discuss the clinical presentation, ancillary procedures and management.