Occurrence Of Second Primary Cancers Research Articles

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.

The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: astatement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

Asignificant 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 25years 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 amore accurate estimation of the occurrence of second primary cancers.

Characterizing Chemotherapy/Radiotherapy-Induced Genome Chaos in Hodgkin's Lymphoma Patients Using M-FISH.

Hodgkin lymphoma (HL) is one of the most common lymphomas, with an incidence of 3 per 100,000 persons. Current treatment uses a cocktail of genotoxic agents, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), along with or without radiotherapy. This treatment regimen has proved to be efficient in killing cancer cells, resulting in HL patients having a survival rate of >90% cancer-free survival at five years. However, this therapy does not have a specific cell target, and it can induce damage in the genome of non-cancerous cells. Previous studies have shown that HL survivors often exhibit karyotypes characterized by complex chromosomal abnormalities that are difficult to analyze by conventional banding. Multicolor fluorescence in situ hybridization (M-FISH) is a powerful tool to analyze complex karyotypes; we used M-FISH to investigate the presence of chromosomal damage in peripheral blood lymphocytes from five healthy individuals and five HL patients before, during, and one year after anti-cancer treatment. Our results show that this anti-cancer treatment-induced genomic chaos that persists in the hematopoietic stem cells from HL patients one year after finishing therapy. This chromosomal instability may play a role in the occurrence of second primary cancers that are observed in 10% of HL survivors. This chapter will describe a protocol for utilizing M-FISH to study treatment-induced genome chaos in Hodgkin's lymphoma (HL) patients, following a brief discussion.

Impact of Psychological Distress on Immune Phenotype in CLL/SLL Patients Managed By Active Observation

Introduction: Asymptomatic patients with a new diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are usually managed by active observation; however, many patients report elevated levels of distress and worry during the ‘watchful waiting’ phase. Psychological distress may have clinical implications given that natural killer [NK] and T cells are not only sensitive to distress, but also critical in controlling disease progression. Thus, the purpose of this study was to examine associations of psychological functioning and quality of life (QOL) with biomarker expression and functional activity of immune cells from peripheral blood of CLL/SLL patients being managed with surveillance. Methods: We conducted a multisite, prospective study in patients with indolent B-cell neoplasms who were managed with surveillance. Participants completed measures of perceived stress (Perceived Stress Scale), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) and quality of life (FACT-G) at study entry and then every 6 months for up to 2 years or disease progression (whichever occurred first). Blood samples were collected at study entry and every 6 months for immune phenotyping using multiparametric flow cytometry (up to 13-color). Biomarkers of activation, viability, proliferation, exhaustion, and receptor expression were assessed on subsets of T, NK, and myeloid cells, and mean fluorescence intensity or percentage of cells staining were determined. Results: Between April 2016 and November 2020, 233 patients were enrolled at two academic institutions in Philadelphia, including 111 with a diagnosis of CLL/SLL. Of these, 76 patients also had viable samples for immune phenotyping. Participants were predominantly male (60.5%) with a mean age of 63.7 years (SD=9.1 years). Approximately 5% self-reported their race as Black or African American and 4% were of Hispanic ethnicity. At enrollment, the median time since diagnosis was 10.6 months (median follow-up time = 23.6 months). Multivariable regression analyses revealed that increased depressive symptoms were associated with a significant shift from lower percentages of non-classical monocytes (NCM) to higher percentages of classical monocytes (CM; see Figure 1). Similar significant population shifts from reduced NCM toward increased CM were also observed with increased levels of stress and anxiety. These results suggest that patients reporting increased stress, anxiety, and depressive symptoms have fewer of the “patrolling” NCM and increased “sensing” CM in peripheral blood. We also assessed expression of numerous innate immune receptors, including DNAM-1, which can stimulate responses by NK and T cells toward tumors. We observed lower expression of DNAM-1 on CD4 + helper T cells and CD8 + cytotoxic T cells in patients with increased depressive symptoms (p< 0.05). Similarly, patients reporting lower QOL also expressed lower levels of DNAM-1 on CD4 + and CD8 + T cells, as well as cytotoxic CD56 dim NK cells (p<0.05). As DNAM-1 is important for antitumor responses, our data suggest that patients with higher depressive symptoms have T and NK cells with reduced capacity to respond to CLL/SLL tumor cells. NKp30, another activating receptor on NK and CD8+ T cells promoting cytotoxicity, was also expressed at lower levels on CD56 dim NK cells and T cells in the peripheral blood of patients reporting depressive symptoms. Patients who reported higher levels of depressive symptoms had lower levels of expression of the activation marker CD69 on CD4+ and CD8+ T cells. Finally, longitudinal analyses revealed that higher levels of depressive symptoms predicted lower levels of PD-L1 on CD56 dim NK cells over time ( p = 0.04). Conclusion: In CLL/SLL patients, psychological functioning is associated with differential patterns of monocyte distribution. Greater depressive symptoms and lower quality of life predicted lower expression of innate immune receptors, such as DNAM-1 on CD4 + helper T cells and CD8 + cytotoxic T cells. Future directions will investigate whether these measures are associated with disease progression or the occurrence of second primary cancers, given the importance of DNAM-1 and NKp30 in immune surveillance for cancers and reactivation of latent viruses. These findings may have direct translational relevance and enable the early identification of patients at-risk for poor outcomes.

Incidence of second primary cancers in oral and pharyngeal cancer patients using a large medical claims database in Japan

Background/purposeAs 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 methodsThis 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. ResultsOf 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. ConclusionPatients 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.

Assessment of Second Primary Cancer Risk Among Men Receiving Primary Radiotherapy vs Surgery for the Treatment of Prostate Cancer

Shared decision-making is an important part of the treatment selection process among patients with prostate cancer. Updated information is needed regarding the long-term incidence and risk of second primary cancer after radiotherapy vs nonradiotherapy treatments, which may help to inform discussions of risks and benefits for men diagnosed with prostate cancer. To assess the current incidence and risk of developing a second primary cancer after receipt of radiotherapy vs nonradiotherapy treatments for prostate cancer. This retrospective cohort study used the Veterans Affairs Corporate Data Warehouse to identify 154 514 male veterans 18 years and older who had localized prostate cancer (tumor stages T1-T3) diagnosed between January 1, 2000, and December 31, 2015, and no cancer history. A total of 10 628 patients were excluded because of (1) incomplete treatment information for the year after diagnosis, (2) receipt of both radiotherapy and a surgical procedure in the year after diagnosis, (3) receipt of radiotherapy more than 1 year after diagnosis, (4) occurrence of second primary cancer or death within 1 year or less after diagnosis, (5) prostate-specific antigen value greater than 99 ng/mL within 6 months before diagnosis, or (6) no recorded Veterans Health Administration service after diagnosis. The remaining 143 886 patients included in the study had a median (IQR) follow-up of 9 (6-13) years. Data were analyzed from May 1, 2021, to May 22, 2022. Diagnosis of a second primary cancer more than 1 year after prostate cancer diagnosis. Among 143 886 male veterans (median [IQR] age, 65 [60-71] years) with localized prostate cancer, 750 (0.5%) were American Indian or Alaska Native, 389 (0.3%) were Asian, 37 796 (26.3%) were Black or African American, 933 (0.6%) were Native Hawaiian or other Pacific Islander, 91 091 (63.3%) were White, and 12 927 (9.0%) were of unknown race; 7299 patients (5.1%) were Hispanic or Latino, 128 796 (89.5%) were not Hispanic or Latino, and 7791 (5.4%) were of unknown ethnicity. A total of 52 886 patients (36.8%) received primary radiotherapy, and 91 000 (63.2%) did not. A second primary cancer more than 1 year after prostate cancer diagnosis was present in 4257 patients (3.0%), comprising 1955 patients (3.7%) in the radiotherapy cohort and 2302 patients (2.5%) in the nonradiotherapy cohort. In the multivariable analyses, patients in the radiotherapy cohort had a higher risk of second primary cancer compared with those in the nonradiotherapy cohort at years 1 to 5 after diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.13-1.37; P < .001), with higher adjusted HRs in the subsequent 15 years (years 5-10: 1.50 [95% CI, 1.36-1.65; P < .001]; years 10-15: 1.59 [95% CI, 1.37-1.84; P < .001]; years 15-20: 1.47 [95% CI, 1.08-2.01; P = .02). In this cohort study, patients with prostate cancer who received radiotherapy were more likely to develop a second primary cancer than patients who did not receive radiotherapy, with increased risk over time. Although the incidence and risk of developing a second primary cancer were low, it is important to discuss the risk with patients during shared decision-making about prostate cancer treatment options.

Risks of Second Primary Gynecologic Cancers following Ovarian Cancer Treatment in Asian Ethnic Subgroups in the United States, 2000-2016.

The differential occurrence of second primary cancers by race following ovarian cancer is poorly understood. Our objective was to determine the incidence of second primary gynecologic cancers (SPGC) following definitive therapy for ovarian cancer. Specifically, we aimed to determine differences in SPGC incidence by Asian ethnic subgroups. We identified 27,602 women ages 20 years and older and diagnosed with first primary epithelial ovarian cancer between 2000 and 2016 who received surgery and chemotherapy in 18 population-based Surveillance, Epidemiology and End Results Program registries. We compared the incidence of SPGC with expected incidence rates in the general population of women using estimated standardized incidence ratios (SIR) and 95% confidence intervals (CI). The incidence of SPGC was lower among White women (SIR = 0.73; 95% CI, 0.59-0.89), and higher among Black (SIR = 1.80; 95% CI, 0.96-3.08) and Asian/Pacific Islander (API) women (SIR = 1.83; 95% CI, 1.07-2.93). Increased risk of vaginal cancers was observed among all women, although risk estimates were highest among API women (SIR = 26.76; 95% CI, 5.52-78.2) and were also significant for risk of uterine cancers (SIR = 2.53; 95% CI, 1.35-4.33). Among API women, only Filipinas had significantly increased incidence of SPGC overall including both uterine and vaginal cancers. Risk of SPGC following treatment of ovarian cancer differs by race and ethnicity, with Filipina women having the highest rates of second gynecologic cancers among Asian women. Ensuring access and adherence to surveillance may mitigate ethnic differences in the early detection and incidence of second gynecologic cancers.

Abstract C020: Racial differences in the risks of second primary gynecologic cancers following chemotherapy for malignant ovarian tumors: Asian subgroups in the United States, 2000-2016

Abstract Objective: The incidence of ovarian cancer in the United States varies by race with the highest rates among white women but lower survival observed among black women and other racial and ethnic groups. These disparities in outcomes among women with ovarian cancer are not well understood, including the differential occurrence of second primary cancers according to race. Our objective was to measure racial differences in incidence of second primary gynecologic cancers (SPGC) among women with malignant ovarian tumors following treatment with chemotherapy. Specifically, we aimed to determine differences in SPGC incidence by Asian ethnic subgroups in the United States. Methods: We conducted a retrospective cohort study of women ages 20 years and older diagnosed with first primary malignant ovarian tumors treated with definitive surgery and chemotherapy between 2000 and 2016 from 18 population-based registries in the Surveillance, Epidemiology and End Results (SEER) Program. We collected demographic and clinical information on ovarian histologic subtypes, laterality, tumor grade, type of surgery and treatment with radiotherapy. Census tract-level sociodemographic characteristics of women were also described. The incidence of SPGC in our cohort was compared to expected incidence rates in the general population using age-and region-standardized incidence ratios (SIRs) and 95% confidence intervals (CI) for individual racial/ethnic groups. Results: Among 34,081 women with ovarian cancer, 74% were white, 6% were black, 8% were Asian/Pacific Islander (API) and 11% were Hispanic. Median age at diagnosis was lower among API and Hispanic women (54 years) compared to white (60 years) and black women (58 years). Most ovarian tumors were serous or endometrioid, although API women had a higher proportion of clear cell ovarian tumors (15%) compared to white (6%), black (5%) and Hispanic women (6%). Subgroups of API women also differed in distribution of ovarian tumor histology, grade, and age at diagnosis. Whereas incidence of SPGC was observed to be lower than expected among white women (SIR 0.72 CI 0.59-0.87), estimates were suggestive of higher than expected incidence among black (SIR 1.61, CI 0.88-2.71) and API women (SIR 1.64, CI 0.96-2.63), although confidence intervals included 1.0. Increased risk of vaginal cancers was observed among all women, although risk estimates were highest among API women (SIR 23.90, CI 4.93-69.84) and were also significant for risk of uterine cancers (SIR 2.28 CI 1.21-3.90). Among API women, only Filipinas had significantly increased incidence of SPGC overall including both uterine and vaginal cancers. Conclusions: Risk of SPGC following treatment of ovarian cancer differs by race. The increased incidence of secondary gynecological cancers observed in Asian women is driven largely by increased rates of uterine and vaginal cancers among Filipina women. Further research is warranted to understand the possible mechanism(s) underlying this observed disparity. Citation Format: Nita H Mukand, Ashwini N Zolekar, Naomi Y Ko, Gregory S Calip. Racial differences in the risks of second primary gynecologic cancers following chemotherapy for malignant ovarian tumors: Asian subgroups in the United States, 2000-2016 [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C020.

Second Primary Cancers in Melanoma Patients Critically Shorten Survival.

BackgroundSurvival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease.MethodsData for melanoma and any SPCs were obtained from the Swedish Cancer Registry for years 2003 through 2015, including clinical TNM classification. SPCs were grouped into three ‘prognostic groups’ based on 5-year relative survival of these cancers as first primary cancer. Kaplan-Meier survival curves were generated and hazard ratios were estimated using Cox regression, adjusted for a number of variables and treating diagnosis of SPC as a time-dependent variable.ResultsThe total number of first melanoma patients was 28,716 followed by 3,202 (11.1%) SPCs, 1/3 of which had a second melanoma while 2/3 had other SPCs. Among men diagnosed at age over 70 years, who survived at least 10 years, 31.4% had SPC. HRs (95% CI) for survival increased systematically from the reference rate of 1.00 (no SPC) to 1.59 (1.35–1.87) with SPC of good prognosis (78.6% of SPCs) to 3.49 (2.58–4.72) of moderate prognosis (12.0%) and to 7.93 (5.50–11.44) of poor prognosis (9.4%). In patients without SPC, the HRs increased to 2.62 (2.02–3.39) with any nodal metastases and to 5.88 (4.57–7.57) with any distant metastases compared to patients without local or distant metastases.ConclusionThe data showed that SPCs are an increasingly common negative prognostic factor for melanoma. Future attempts to improve melanoma survival need to target SPCs.

Effect of second primary cancer on the prognosis of patients with non-small cell lung cancer.

Second primary cancer (SPC) is not a rare event for patients with non-small cell lung cancer (NSCLC), especially for those who survive for a longer period of time. This study was aimed to explore the effects of SPC on the survival of NSLCL patients. A total of 241,805 patients with primary NSCLC were identified between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence of SPC and its effect on the overall survival (OS) and lung cancer-specific survival (LCSS) was explored and analyzed using Cox regression model with SPC being treated as a time-dependent covariate. The incidence of SPCs after the diagnosis of NSCLC was 6.4%, with the second primary lung cancer being the most common one (45.1%). About half of the SPCs (50.7%) occurred during the first year after the diagnosis of NSCLC. It seemed that patients who developed SPC late in the follow-up period tended to have poor prognosis. Multivariable analysis with Cox regression showed that the occurrence of SPC was a poor prognostic factor for patients with NSCLC [hazard ratio (HR), 1.298; 95% confidence interval (CI), 1.270-1.326; P=0.000], and it increased the risk of LCSS (versus no SPC, HR, 1.094; 95% CI, 1.066-1.123; P=0.000). The occurrence of SPC after the diagnosis of NSCLC was not a rare event, and it indicated a poorer prognosis compared with patients without it. During the follow-up, attention should be paid to the screening of SPC especially the second primary lung cancer, and a rational surveillance policy should be formed and implemented.

Second primary cancers in patients with acute lymphoblastic, chronic lymphocytic and hairy cell leukaemia.

Improvement of survival in lymphocytic leukaemia has been accompanied by the occurrence of second primary cancer (SPCs). Based on Swedish Family Cancer Database, we applied bi-directional analyses in which relative risks (RRs) were calculated for any SPCs in patients with chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL) and hairy cell leukaemia (HCL) and the risks of these leukaemias as SPCs. After CLL, RRs were significant for 20 SPCs, and high for skin squamous cell cancer (24·58 for insitu and 7·63 for invasive), Merkel cell carcinoma (14·36), Hodgkin lymphoma (7·16) and Kaposi sarcoma (6·76). Conversely, 15 CLL cancer pairs were reciprocally increased. The increased risks were reciprocal for ALL and four cancers. RR for ALL was 15·35 after myeloid neoplasia. HCL showed reciprocally increased RRs with non-Hodgkin lymphoma and melanoma. The concordance between RRs for bi-directional associations between CLL and different cancers, and HCL and different cancers was highly significant. For CLL (also for HCL), the bi-directional risks with skin cancers and other immune-related cancers suggest the probable involvement of immune dysfunction. For ALL, treatment may contribute to risks of multiple SPCs. Increased risk of ALL after haematological neoplasms may indicate bone marrow dysfunction. These findings may help guide treatment decisions and prognostic assessment.

Conventional Western Treatment Associated With Chinese Herbal Medicine Ameliorates the Incidence of Head and Neck Cancer Among Patients With Esophageal Cancer.

Background: Because of advances in medical treatment, the survival of cancer patients is prolonged. In line with the prolonged survival time of cancer the incidence of second primary cancer has increased. There is currently no effective way to prevent the occurrence of secondary primary cancer (SPC). Objectives: The aim of this study is to evaluate whether Chinese Herbal Medicine (CHM) is correlated with reduced occurrence of second primary cancer (SPC) of head and neck (H&N) in patients with esophageal cancer (EC). Method: We identified 15,546 patients who were diagnosed with esophageal cancer between Jan 1, 2000, and Dec 31, 2010. The patients with H&N cancer before receiving CHM were excluded. After the selection and matching process, both CHM and non-CHM cohorts each contained 850 individuals. We compared the cumulative incidence of SPC of H&N with or without CHM treatment in patients with EC by the Kaplan-Meier method. NodeXL is used to run a network analysis of CHM to examine the association between herbs and formulas. Results: Compared with non-CHM users, CHM-users showed a reduced incidence rate of SPC of H&N among the patients with EC. Reduced cumulative incidence of SPC of H&N among patients with EC was noted in the CHM cohort compared to the non-CHM cohort. The most commonly used single herbs and formulas were associated with reducing SPC occurrence. Conclusion: We propose that CHM as an adjuvant therapy may prevent the occurrence of SPC of H&N in patients with EC.

Predictors of circulating INTERLEUKIN-6 levels in head and neck cancer patients

BackgroundCirculating interleukin-6 (IL-6) improves outcome prediction for second primary cancer (SPC) in head and neck cancer (HNC) patients. This study aimed to identify factors associated with IL-6 serum levels in HNC patients.MethodsThis study was conducted as part of a phase III chemoprevention trial. IL-6 was measured using chemiluminescent immunometric assay on pretreatment serum sample obtained from 527 stage I-II HNC patients. Patients’ lifestyle habits, sociodemographic, medical and tumor characteristics were evaluated before radiation therapy (RT). Factors independently associated with IL-6 levels before RT were identified using multiple linear regression.ResultsThe median IL-6 serum level was 3.1 ng/L. In the multivariate analysis, eight factors were significantly associated (p < 0.05) with IL-6: age, gender, marital status, body mass index, tobacco consumption, comorbidities, Karnofsky Performance Status and HNC site. Smoking duration and lifetime pack-years were positively associated with IL-6 serum levels in a dose-response relationship (p-value for trend ≤0.03).ConclusionsCirculating IL-6 is a strong predictor of the occurrence of SPC in HNC patients. We identified eight factors independently associated with serum IL-6 levels in 527 stage I-II HNC patients.The dose-response relationship between lifetime smoking and IL-6 serum levels suggested a causal role of tobacco exposure on IL-6 production. Further studies are needed to establish whether the effect of tobacco exposure on SPC could be partly mediated by IL-6, a pro-inflammatory cytokine.

Relationships Between Serum IL-6, Tobacco Consumption, and the Occurrence of Second Primary Cancers in Head and Neck Cancer Patients

Relationships Between Serum IL-6, Tobacco Consumption, and the Occurrence of Second Primary Cancers in Head and Neck Cancer Patients

Facial flushing after alcohol intake as a predictor for a high risk of synchronous or metachronous cancer of the upper gastrointestinal tract.

In Japan, there has been a lot of reports showing an association between facial flushing after light alcohol consumption and heterozygosity for inactive aldehyde dehydrogenase-2 (ALDH2). Persons with inactive ALDH2 may have a higher risk of alcohol-related oral, pharyngeal and esophageal cancers, compared with those with wild-type ALDH2. The purpose of this study was to examine whether flushers with oral or pharyngeal squamous cell carcinoma have an increased risk of synchronous or metachronous cancer of the upper gastrointestinal (UGI) tract. A retrospective study was performed by medical chart review and through a questionnaire sent to 285 patients treated for oral and pharyngeal cancer. Responses were obtained from 150 patients (52.6%), who were classified as flushers or non-flushers, smokers (≥20 pack-year; 1 pack-years = number of cigarettes/20 per day) or non-smokers, and drinkers (≥14 units of alcohol consumption per week; 1 unit = 22 g) or non-drinkers. Relationships of these factors with occurrence of second primary cancers (SPCs) in the UGI tract were investigated. In Kaplan-Meier analysis, there was a significantly higher rate of SPC at 5 years in flushers and drinkers, but no relationship with smoking. In multivariate analyses, a history of flushing was significantly associated with SPC in the UGI tract (HR 2.64, 95% CI 1.25-5.52, P = 0.0109), but not with smoking or alcohol consumption. A simple interview on history of facial flushing after alcohol intake can be useful for identifying patients at high risk for synchronous or metachronous cancers of the UGI tract.

Occurrence of second primary cancer after curative resection of cholangiocarcinoma: a report of 5 cases

The second primary cancer, a new cancer subsequent to the initial cancer, usually occurs in a person who has a history of cancer or the patient treated with curative resection. Although the pathogenesis of second primary cancer is unclear, it is always found that occurrence of second primary cancer is related to the age and family history. In our 5 cases’ reports, second primary cancer occurs after curative resection of cholangiocarcinoma. And most of the second primary cancers belong to well differentiated adenocarcinomas which grow slowly and never metastasize distally in early stage. Therefore, operative excision is the most effective treatment. At the same time, conventional examination after operation could improve early diagnosis and timely surgical treatment.

Second Primary Cancers After Primary Breast Cancer Diagnosis in Israeli Women, 1992 to 2006.

PurposeImprovements in early detection and treatment have resulted in improved long-term survival from breast cancer, which increases the likelihood of the occurrence of second primary cancers. We calculated the risk of second primary cancers among Israeli women receiving a first primary breast cancer diagnosis.MethodsBy using data from the Israel National Cancer Registry, we identified 46,090 women with invasive breast cancer diagnosed between 1990 and 2006 and non–breast primary cancers diagnosed subsequent to breast cancer diagnosis. We used life table analysis to calculate the risk of a second primary cancer and calculated standardized incidence ratios (SIRs) by using age-specific cancer risk in the general population of Israeli women as the standard and stratifying by diagnosis period (1992 to 1996, 1997 to 2001, 2002 to 2006) and age at diagnosis (< 50 and ≥ 50 years).ResultsThe probability of a second malignancy was 3.6% within 5 years, 8.2% within 10 years, and 13.9% within 15 years. The SIR for any second non–breast primary cancer was 1.26 (95% CI, 1.23 to 1.30). Significantly increased risks of colorectal, uterine, lung, ovarian, and thyroid cancer and leukemia were observed for the full follow-up period, which persisted after excluding the first 6 months after index diagnosis, although increased leukemia and colorectal cancer risks were no longer statistically significant. Women younger than age 50 years at initial diagnosis had a greater excess risk than women age 50 years and older (SIR, 1.77 [95% CI, 1.63 to 1.91] and 1.20 [95% CI, 1.15 to 1.24], respectively).ConclusionThe findings likely reflect a combination of personal risk factors (genetics, hormonal therapy, environmental exposures) as well as the effects of the initial cancer treatment and are unlikely to be explained by enhanced surveillance alone.

Effect of metformin on progression of head and neck cancers, occurrence of second primary cancers, and cause-specific survival.

This study aimed to investigate the effect of metformin on progression of head and neck cancers, occurrence of second primary cancers, and cause-specific survival. This study analyzed a retrospective cohort of 1,151 consecutive patients with head and neck squamous cell carcinoma who were treated at our hospital. Patients were divided into three groups: nondiabetic, nonmetformin, and metformin. Clinical characteristics, recurrence of index head and neck cancer, occurrence of second primary cancer, and survival were compared among the different groups. Of 1,151 patients, 99 (8.6%) were included in the metformin group, 79 (6.8%) were in the nonmetformin group, and 973 (84.5%) were in the nondiabetic group. Diabetic status and metformin exposure had no significant impact on index head and neck cancer recurrence or second primary cancer development (p > .2). The nonmetformin group showed relatively lower overall (p = .017) and cancer-specific (p = .054) survival rates than the other groups in univariate analyses, but these results were not confirmed in multivariate analyses. Metformin use did not show beneficial effects on index tumor progression, second primary cancer occurrence, and cause-specific survival in patients with head and neck cancer compared with nonmetformin users and nondiabetic patients.

Genetic features of metachronous esophageal cancer developed in Hodgkin's lymphoma or breast cancer long-term survivors: an exploratory study.

BackgroundDevelopment of novel therapeutic drugs and regimens for cancer treatment has led to improvements in patient long-term survival. This success has, however, been accompanied by the increased occurrence of second primary cancers. Indeed, patients who received regional radiotherapy for Hodgkin’s Lymphoma (HL) or breast cancer may develop, many years later, a solid metachronous tumor in the irradiated field. Despite extensive epidemiological studies, little information is available on the genetic changes involved in the pathogenesis of these solid therapy-related neoplasms.MethodsUsing microsatellite markers located in 7 chromosomal regions frequently deleted in sporadic esophageal cancer, we investigated loss of heterozygosity (LOH) and microsatellite instability (MSI) in 46 paired (normal and tumor) samples. Twenty samples were of esophageal carcinoma developed in HL or breast cancer long-term survivors: 14 squamous cell carcinomas (ESCC) and 6 adenocarcinomas (EADC), while 26 samples, used as control, were of sporadic esophageal cancer (15 ESCC and 11 EADC).ResultsWe found that, though the overall LOH frequency at the studied chromosomal regions was similar among metachronous and sporadic tumors, the latter exhibited a statistically different higher LOH frequency at 17q21.31 (p = 0.018). By stratifying for tumor histotype we observed that LOH at 3p24.1, 5q11.2 and 9p21.3 were more frequent in ESCC than in EADC suggesting a different role of the genetic determinants located nearby these regions in the development of the two esophageal cancer histotypes.ConclusionsAltogether, our results strengthen the genetic diversity among ESCC and EADC whether they occurred spontaneously or after therapeutic treatments. The presence of histotype-specific alterations in esophageal carcinoma arisen in HL or breast cancer long-term survivors suggests that their transformation process, though the putative different etiological origin, may retrace sporadic ESCC and EADC carcinogenesis.

Abstract C87: Risk of second primary cancer (SPC) after breast cancer: A pooled analysis of Hispanic and non-Hispanic white women from New Mexico

Abstract Breast cancer is the most common form of cancer diagnosed among women. With the advances in early detection and breast cancer treatment, the population of long-term survivors is growing. Breast cancer survivors have increased risk of developing a second primary cancer (SPC) relative to a first primary cancer. Several population-based studies have examined the associations of specific risk factors, such as radiation treatment, with risk of SPC; however, few have investigated ethnic/racial differences in risk, or have examined the associations with modifiable risk factors such as smoking or obesity. We evaluated the risk of SPC among Hispanic (H) and non-Hispanic white (NHW) women from a pooled sample of 1,699 (1011 NHW, 688 H) incident breast cancer cases from the New Mexico Women's Health Study (1992-1994) and the 4-Corner's Breast Cancer Study (1999-2004). Data on lifestyle/behavioral risk factors, cancer diagnoses/characteristics, and primary breast cancer treatment were available. Adjusted Cox regression models were calculated to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of SPC with ethnicity, age at first primary breast cancer diagnosis, cigarette smoking history, and obesity (body mass index (BMI)≥30 kg/m2). Multivariable models were adjusted for age, study site/center, ethnicity, and breast cancer treatment. There were a total of 223 cases with SPC. There was no difference between NHW and H women for occurrence of SPC (13.5% vs. 12.7%; chi. sq. p=0.63) or the average number of years from first primary to SPC (H= 9.8 years vs. NHW= 9.5 years, p=0.102). The most common SPC observed was secondary primary breast cancer (n=117), followed by lung (n=15) and colon cancer (n=15). Obesity was not significantly associated with risk of SPC. However, women 50 years or older were at an increased risk for SPC compared to women under age 50 (HR, 1.67, 95% CI 1.23-2.28, p=0.001). With the evaluation of smoking history, former smokers had longer durations of smoking compared to current smokers; however, current smokers, compared to former, smoked on average more cigarettes/day. Compared to never smokers, women who smoked more than 20 pack-years (HR, 1.61; 95% CI 1.16-2.24, p=0.02), an average of 20 or more cigarettes/day (HR, 1.52; 95% CI 1.10-2.10, p=0.09), or for more than 30 years (HR, 1.69; 95% CI 1.19-2.40, p=0.03) had increased risk for SPC. Women who were ever smokers vs. never smokers also had an increased risk for SPC (HR, 1.35; 95% CI 1.04-1.76, p=0.03). The association among current smokers was not statistically significant (HR, 1.27; 95% CI 0.94-1.71), but there was a significant positive association found for former smokers (HR, 1.52; 95% CI 1.06-2.18, p=0.05). Our results suggest that women diagnosed with primary breast cancer are more likely to develop SPC if they are over the age of 50 years at diagnosis or have a history of cigarette smoking. These results were statistically significant after adjustment for breast cancer treatment. These findings further suggest that smoking cessation programs or interventions should be clinically advised for breast cancer survivors, as this population of women is at an increased risk for developing SPC. Citation Format: Avonne E. Connor, Richard N. Baumgartner, Stephanie D. Boone, Christina M. Pinkston, Kathy B. Baumgartner. Risk of second primary cancer (SPC) after breast cancer: A pooled analysis of Hispanic and non-Hispanic white women from New Mexico. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C87. doi:10.1158/1538-7755.DISP13-C87