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Patients with known tumors can have other tumors in unexpected places, the so-called synchronic or second primary cancers. In these patients, whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) to study known tumors can identify other tumors that would escape notice if only the sites of known tumors were investigated. We present 3 patients in whom whole-body FDG-PET was requested to study known tumors: 2 lung cancers and one melanoma. FDG-PET localized the known lesions and revealed hypermetabolic uptake in the abdomen in all 3 patients. Endoscopic polypectomy and pathologic analysis were performed, revealing 2 colon cancers and a tubular adenoma with a high degree of focal atypia. Whole body FDG-PET is a highly useful technique in the early diagnosis of colorectal cancer, which in turn allows complete cure of patients with this disease.

Aims Prostate brachytherapy may be associated with a lower risk of radiation-induced second primary cancer (SPC) as a significantly smaller volume of normal tissue is irradiated when compared with external beam techniques. Limited data are available as it has been a routine treatment option for less than 20 years. This study identified cases of SPC in patients who underwent I-125 prostate brachytherapy as monotherapy in a single institution. Materials and methods SPC incidence was retrieved by conducting a UK cancer registry search (Northern and Yorkshire Cancer Registry and Information Service) for 1805 consecutive patients with localised prostate cancer who received monotherapy with I-125 brachytherapy from 1995 to 2006 at a single public hospital. Of 1730 UK residents, the completeness of the registry match was 91% (1574 patients). The mean age at treatment (interquartile range) of the cohort was 63 (58–68) years with 1100 patients (70%) over the age of 60 years at treatment. The median (range) follow-up was 8 (6–10) years with 487 patients (31%) having 10 years or more. Results In total, 170 patients (10.8%) were diagnosed with second primaries (1 year or more after implant); 20 of these were bladder and 10 rectal cancers. The 10 year cumulative incidences were 14.6, 1 and 0.84% for any second malignancy, bladder and rectal cancer, respectively. Only the standardised incidence rate (SIR) for bladder cancer was higher at 1.54 (95% confidence interval 0.96–2.46) compared with the general population. The SIR for bladder cancer was higher in the first few years after treatment, suggesting that the increased incidence of bladder cancer is due to increased urological surveillance. Conclusions Overall, the incidence of SPC after I-125 is comparable with other published data with no significant excess more than 5 years from treatment. Mortality secondary to SPC of the bladder or rectum is unusual.

A review of planning studies was undertaken to evaluate estimated risks of radiation induced second primary cancers (RISPC) associated with different prostate radiotherapy techniques for localised prostate cancer. A total of 83 publications were identified which employed a variety of methods to estimate RISPC risk. Of these, the 16 planning studies which specifically addressed absolute or relative second cancer risk using dose–response models were selected for inclusion within this review. There are uncertainties and limitations related to all the different methods for estimating RISPC risk. Whether or not dose models include the effects of the primary radiation beam, as well as out-of-field regions, influences estimated risks. Regarding the impact of IMRT compared to 3D-CRT, at equivalent energies, several studies suggest an increase in risk related to increased leakage contributing to out-of-field RISPC risk, although in absolute terms this increase in risk may be very small. IMRT also results in increased low dose normal tissue irradiation, but the extent to which this has been estimated to contribute to RISPC risk is variable, and may also be very small. IMRT is often delivered using 6MV photons while conventional radiotherapy often requires higher energies to achieve adequate tissue penetration, and so comparisons between IMRT and older techniques should not be restricted to equivalent energies. Proton and brachytherapy planning studies suggest very low RISPC risks associated with these techniques. Until there is sufficient clinical evidence regarding RISPC risks associated with modern irradiation techniques, the data produced from planning studies is relevant when considering which patients to irradiate, and which technique to employ.

Second cancer in a women with a primary gynecological malignancy could reflect a common etiology or sequealae of a potentially carcinogenic treatment. The aim of the present study was to determine the incidence rate of second primary cancer in a cohort of women with primary gynecological cancer and patient characteristics, namely age, diagnosis, type of treatment, and duration of follow-up. The study cohort comprised 925 Israeli Jewish women with histologically confirmed gynecologic malignancies. The file was linked by computer matching to the Israel Cancer Registry for identification of second primary cancers. Standardized incidence rates (SIRs) for site-specific as well as for all cancer were computed. A significant excess for subsequent leukemia among ovarian (SIR 10; 95% CI 1.1–36.1) and uterine corporal cancer patients (SIR 10.0; 95% CI 2.7–25.6) was found. The significant increase in leukemia was treatment-related and limited to patients treated with radiotherapy. Age older than 60 years constituted a significantly unfavorable factor. The estimated probability of developing a subsequent cancer at 175 months is 6.1%. Physicians should be aware of the possibility of a second primary malignancy when prescribing treatment and during follow-up.

About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excessive consumptions of tobacco and/or alcohol are recognized as risk factors of second primary cancers in these patients. Epidemiologic studies suggest that antioxidant vitamins could have a protective effect on the occurrence of second primary cancers; however, this hypothesis should be confirmed by randomized clinical trials. A better knowledge of the risk factors of second primary cancers in patients with a pharyngeal cancer could help reducing the occurrence of second primary cancers and improving the follow-up of these patients.

A marked increase in cancer survival and in the frequency of second primary cancers (SPCs) has been observed in the latest decades, propelling the investigation of their burden at a population level. We aimed to quantify the proportion of SPCs among the incident cases in North Portugal and to describe their survival. We identified all SPCs (excluding skin nonmelanoma) registered by the North Region Cancer Registry (RORENO) from 2000 to 2003 according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. We classified tumors diagnosed more than 2 months after a first primary cancer (FPC) as metachronous. The observed survival was computed using vital status in December 2010. A total of 1607 SPCs (3.8% of all cancers) were registered (77.9% metachronous). The most frequent metachronous SPC topographies and the corresponding most frequent FPCs were of the colon (12.2%; FPC: prostate, breast, and stomach), lung (10.5%; FPC: bladder, stomach, and colon), and stomach (9.7%; FPC: prostate, breast, and bladder). The overall 5-year survival of individuals with metachronous SPCs was 47.4%; within the subgroups with higher (63.1%) and lower survival (31.1%), there were no significant differences across groups of FPCs with expectably different survival. The proportion of SPCs was that anticipated for a registry with approximately one decade of activity. The most common cancers in the general population were also frequent metachronous SPCs, whereas the most frequent FPCs were high incidence and survival cancers. The survival of metachronous SPCs did not vary with the survival expected for the FPCs., L.F. received a grant from the Fundação para a Ciência e a Tecnologia (SFRH/SINTD/60124/2009).

Background Adolescents and young adults (AYA; aged 15-39) treated for first cancers are a demographic cohort that are uniquely predisposed to risk of second cancers. This is due to increased sensitivity of exposed tissues to cancer therapies and a longer latency for the development of second cancers due to longer survival resulting from advances in cancer treatments. Radiotherapy is a commonly used modality in several AYA cancers and has been associated with increased risk of subsequent neoplasms including myeloid malignancies. Myelodysplastic syndrome (MDS) is the most common myeloid malignancy in the US but very little is known regarding the risk of MDS in the AYA population. In this study, we analyzed the evolving risk of MDS in the AYA population spanning over 4 decades using the US Surveillance Epidemiology and End Results (SEER) registry. Methods A novel R program, SEERaBomb (Leukemia. 2016;30(2):285-94) was developed to query all 18 SEER registries. We identified all AYA first cancer cases treated with radiation that subsequently developed MDS as second cancers. Diagnosis was derived from the International Classification of Diseases for Oncology Third Revision categories. SEER cancer registries collect information on the initial course of treatment and does not carry information on chemotherapy. SEERaBomb allows merging of all 18 SEER registries - a function not permitted by the NIH-developed SEER*Stat MP-SIR program that limits researchers to use either SEER 9 or SEER 13. This significantly increases the capture of MDS cases. AYA cancer survivor person yrs at risk for developing MDS was based on age at diagnosis of the first cancer, survival time, and age at diagnosis of MDS. Relative risks (RR) for developing MDS were based on observed/expected cases between the cohorts receiving no radiation (control) or radiation. Results In total 569,681 AYA first cancer patients (pts) were identified, of whom 133,829 (23%) received radiation as initial part of their cancer treatment and 426,272 (75%) received no radiotherapy. Mean age at the time of first cancer diagnosis was similar in radiation treated and untreated cohorts (32 yrs vs. 31.2 yrs). Median yrs of follow up after first cancer diagnosis was 5.7 yrs (25-75 interquartile [IQR], 1.9-12.2) in pts receiving radiation and 9.1 yrs (25-75 IQR, 2.7-20.2) in those not treated with radiation. A total of 48 pts developed MDS; 21 in the radiation group and 27 in the cohort that did not receive radiation. Median time to development of MDS after first cancer diagnosis was 3.8 yrs (25-75 IQR, 2.0-6.1) in those who received radiation and 3.1 yrs (25-75 IQR, 1.1-4.2) in non-irradiated pts. MDS cases were classified as RA (n=5), RARS (n=4), RCMD (n=3), RAEB (n=8), MDS with 5q deletion syndrome (n=2), and MDS-U (n=26). Compared with the risk in general population, pts treated with radiotherapy and those who did not receive radiation had an elevated risk of developing MDS within the first 10 yrs (RR=33.3; 95% CI, 20.4-51.5 vs. RR=19.3; 95% CI, 12.6-28.2). The risk of MDS in both radiation-treated and untreated cohort peaked within the first two yrs. The risk of MDS in general was higher in the radiation-treated pts compared to non-radiated pts for up to 7 yrs from exposure and beyond 10 yrs, the risk for MDS steadily fell to baseline rates (Fig 1). The risk kinetics of developing MDS in AYA first cancer survivors mimics the kinetics of MDS development in adults > 40 yrs, whereas the magnitude of the RR is much higher in the first group (Fig 2). When the pooled occurrence of AML and MDS as second cancers was analyzed in AYA first cancer survivors, those who received radiation had a statistically significant increased risk of developing AML or MDS within the first 3 yrs of exposure compared with pts not treated with radiation (RR=22.5; 95% CI, 18.2-27.7 vs. RR=12.5; 95% CI,10.3-15.0; Fig 3). Conclusion AYA cancer pts have a strikingly increased risk of developing MDS in the first 10 yrs after first cancer diagnosis. AYA cancer pts undergoing radiotherapy for first cancers appear to have an even higher risk of developing MDS that can last up to 10 yrs following exposure. Considering the long latency of MDS seen in atomic bomb cohorts and relative young age of AYA pts, MDS rates are likely to continue to rise. Figure 1 Kinetics of MDS second cancer risks in AYA pts. Figure 1. Kinetics of MDS second cancer risks in AYA pts. Figure 2 Kinetics of MDS second cancer risks in patients aged > 40 yrs. Figure 2. Kinetics of MDS second cancer risks in patients aged > 40 yrs. Figure 3 Kinetics of myeloid neoplasm (MN; MDS or AML) second cancer risks in AYA pts. Figure 3. Kinetics of myeloid neoplasm (MN; MDS or AML) second cancer risks in AYA pts. Disclosures Carraway: Baxalta: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau. Maciejewski:Celgene: Consultancy, Honoraria, Speakers Bureau; Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding.

Second Primary Cancers and Cardiovascular Disease after Radiation Therapy. NCRP Report No. 170. NCRP Publications, Bethesda, MD, 2011. $160.00. ISBN: 978-0-9823843-9-8, 386, pp. (hardcover).

In unsparing efforts to find the hidden primaries, second primary cancers (SPCs) unrelated to cancer of unknown primary (CUP) are found. The detection rates of SPCs after CUP can be considered as measures for the effectiveness of modern diagnostic techniques in finding tumors. We aimed to compare the rates of specific SPCs found after the work-up of CUP and the more sign/symptom-directed diagnostic approaches applied after any other cancer. The number of CUP patients identified in the nationwide Swedish database and nine German cancer registries was 24 641 from 1997 through 2006, and rate ratios (RRs) for SPCs were recorded in two follow-up periods. The detection rate of SPCs immediately after any other cancer was about two times higher in Germany than in Sweden, but the rate immediately after CUP was almost the same for the two datasets. In the joint analyses after CUP, the RRs of liver, lung, breast, and kidney cancers were higher than after any other cancer, whereas the RRs of prostate, urinary bladder, and connective tissue cancers as well as non-Hodgkin's lymphoma were not significantly different; the RR of cancers of upper aerodigestive tract was lower after CUP than after any other cancer. The joint data indicate that the work-up is efficient in detecting tumors in the thoracoabdominal organs that are screened by computed tomography. For some other organ sites, the more sign/symptom-directed diagnostic approaches may be equally efficient. However, none of the applied techniques could detect all tumors immediately after the first diagnosis.

Introduction This article presents the case of a 26-year-old woman with tongue cancer. The median age at the diagnosis of the tongue’s cancer is 61 years. Only approximately 2% of patients are diagnosed before the age of 35. Case presentation Our patient survived acute myeloid leukemia (AML) before her second year. She had been having recurrent, poorly healing aphtae on the right side of the tongue for a period of months before the symptoms of the tongue cancer appeared. As a treatment a partial glossectomy was conducted on the right side and a neck dissection of levels I-III. Than a reconstruction of the tongue with a radialis free vascularised flap from left side was performed. Discussion It should be always looked for the causal factor in young patients with a neoplasm. There is strong evidence for second malignant neoplasms in survivors of childhood cancer.

BACKGROUND The survival of patients with renal cell carcinoma (RCC) has improved in recent years. However, data on the risk of developing a second cancer after a diagnosis of RCC is limited. We used the data available in the Surveillance Epidemiology and End Results (SEER) database to estimate the risk of second metachronous primary cancers in patients diagnosed with RCC between 1973 and 2006. Furthermore, we also investigated the effect of the second primary cancers (SPCs) on the survival of RCC patients. RESULTS A total of 3795 cases of SPCs were registered in the SEER between 1973 and 2006. The ratio of observed/expected number of SPCs in RCC was 1.18, which was significantly greater than expected. Solid tumors comprised 90% of all second malignancies in RCC patients, with the most second cancers reported in the prostate gland and the digestive and respiratory systems. The overall risk of second primaries was highest in patients aged over 30 years at the time of diagnosis. The site-specific risk of second cancers varied with the age at diagnosis, sex, race of the patient, size of the primary renal tumor, and history of radiation therapy. Patients with second primaries had a significantly longer overall survival than those without second malignancies. An interval of

To investigate the possible relationship between dietary factors and the development of multiple primary cancer, a nested case-control study was carried out within a cohort of 1,090 oral and pharyngeal cancer patients. This patient group, enrolled in 1984-1985 in a population-based case-control study conducted in four areas of the United States, was followed up through June 1989 for the occurrence of second primary cancer. Information on a number of risk factors, including diet, ascertained from interviews conducted at baseline (1984-1985) and at follow-up were compared between 80 patients with histologically confirmed second primary cancers (39% in the upper aerodigestive tract, 32% in the lung, 29% elsewhere) and 189 sex- and survival-matched control patients free of second cancers. Although few significant trends emerged, the results were suggestive of a protective effect provided by higher intake of vegetables. Risk of second primary cancers was 40-60% lower among those with the highest levels of intake for total vegetables and most vegetable subgroups, including dark yellow, cruciferous, and green leafy vegetables and legumes. Risks were also nonsignificantly lower among those with high consumption of vitamin C and carotenoids, with the adverse effects of alcohol being most evident among heavy drinkers with low vitamin C or carotenoid intake. There was also some evidence of an interaction between smoking and vitamin C consumption, but numbers of nonsmokers were small. Among other dietary factors considered, positive associations were found with increasing consumption of meats, liver, and retinol. The findings suggest that dietary factors contribute along with alcohol and smoking to the excess risks of second primary cancers among patients with oral and pharyngeal cancers.

Acute leukemia after myeloma has been attributed to exposure to alkylating agents. However, leukemia is now being seen in patients receiving lenalidomide maintenance therapy. Patients with monoclonal gammopathy of undetermined significance also have an increased risk of leukemia without ever being treated.

Background Cancer survivors face an increased likelihood of being subsequently diagnosed with another cancer. The aim of this study was to quantify the relative risk of survivors developing a second primary cancer in Queensland, Australia. Methods Standardised incidence rates stratified by type of first primary cancer, type of second primary cancer, sex, age at first diagnosis, period of first diagnosis and follow-up interval were calculated for residents of Queensland, Australia, who were diagnosed with a first primary invasive cancer between 1982 and 2001 and survived for a minimum of 2 months. Results A total of 23,580 second invasive primary cancers were observed over 1,370,247 years of follow-up among 204,962 cancer patients. Both males (SIR = 1.22; 95% CI = 1.20-1.24) and females (SIR = 1.36; 95% CI = 1.33-1.39) within the study cohort were found to have a significant excess risk of developing a second cancer relative to the incidence of cancer in the general population. The observed number of second primary cancers was also higher than expected within each age group, across all time periods and during each follow-up interval. Conclusions The excess risk of developing a second malignancy among cancer survivors can likely be attributed to factors including similar aetiologies, genetics and the effects of treatment, underlining the need for ongoing monitoring of cancer patients to detect subsequent tumours at an early stage. Education campaigns developed specifically for survivors may be required to lessen the prevalence of known cancer risk factors.

WOS:000284263900006 PubMed: 22933922 Background. The risk of developing a second primary tumour in patients with gastric carcinoma is higher than among the general population. The aim was to investigate the clinicopathological characteristics of the second primary cancers in patients with gastric cancer in this study. Patients and methods. In the retrospective study, patients with gastric cancers were evaluated between 1995 and 2005 for primary tumours according to Warren and Gates' criteria related with the second primary cancers. Results. Nine of the 112 patients with gastric cancer had second primary cancers. Seven of the patients were males and two females. Six patients with gastric cancers had synchronous, and three had metachronous tumours. The age of the patients ranged from 53 to 78 years, and the mean age was 61 +/- 8.3 years. The most frequent site of occurrence of the second tumours was the colo-rectum (33%) followed by the upper respiratory system (22%), and the urogenital system (22%) in descending order of frequency. Conclusions. The incidence of the second primary cancer in gastric cancer patients was 8% in the current report. It is recommended that careful preoperative and postoperative examinations for other primary cancers, as well as for the extent of the primary gastric carcinoma, are carried out. Because colorectal cancer was the most common carcinoma combined with gastric carcinoma, the surveillance for this carcinoma (e.g., colonoscopy, abdominopelvic CT) would be appropriate after the diagnosis of gastric carcinoma.

The purpose of this study was to investigate clinically useful information for effective screening for synchronous and metachronous second primary cancers and to suggest potential surveillance tool.We retrospectively reviewed 1,063 patients who were treated with potentially curative surgery for colorectal cancer at Gachon University, Gil Hospital from 1997 to 2007.The incidence of synchronous or metachronous cancer in addition to colorectal cancer was 5.3% (57 patients). The most common second primary cancer was stomach (54.3%), followed by cancers in cervix (12.2%). The time interval between the first and second tumor in colorectal cancer associated with metachronous extracolonic malignancy ranged from 1.1 to 10.8 years. The incidence of early-stage tumor was higher in patients with synchronous cancer than in those with a metachronous cancer with statistical significance (p = 0.034). The 5-year survival rate of the colorectal cancer group without second primary cancer was 70.1%, whereas that for the second primary cancer group was 63.8% (p = 0.253). The 5-year survival rate of the colorectal cancer group with stomach cancer was 70.5%, whereas that for the second primary cancer other than stomach cancer group was 56.6% (p = 0.282).The frequent association between colorectal cancer and gastric cancer suggests an inclusion of gastrofiberscope when surveillancing patients with colorectal cancer in Korean population. Second primary cancers may develop even 10 years after the initial operation; thus, a need for lifelong surveillance even more than 5 years may be necessary.

Head and neck cancer provides a unique model for the study of chemoprevention. The retinoids and other agents have established activity in oral premalignancy. The retinoids have recently been shown to decrease the frequency of second primary cancers in the aerodigestive tract. Biomarker evaluation as intermediate end points shows potential in facilitating future chemoprevention clinical trials.

Second primary cancers occur in ∼ 12% of women with an initial breast cancer diagnosis. This study assessed predictors of the risk of developing a second primary cancer after breast cancer. The analysis included 335,191 females, registered in the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database, who had been diagnosed with breast cancer. Observed numbers of subsequent cancers in the SEER database with a first breast cancer diagnosed from 1973 to 2000 were compared with the expected numbers based on age-adjusted incidence rates to calculate standardized incidence ratios. Kaplan-Meier curves were conducted to determine the median time until the second primary cancer diagnosis.

Substantial improvements in the past few decades in cancer detection and supportive care along with advances in therapy have led to growing numbers of cancer survivors. In view of the prolongation of survival in increasing numbers of patients, identification and quantification of the late effects of cancer and its therapy have become critical. One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. The number of patients who have second or higher-order cancers is increasing, and solid tumors are a leading cause of mortality among several populations of long-term survivors, including patients who have Hodgkin lymphoma. The focus of this article is treatment-associated malignancies in survivors of selected adult cancers.

Publisher Summary Radiation is one of the most extensively researched carcinogens, and induction of carcinogenesis by low doses of radiation (1-10 Gy) has been demonstrated by the significantly higher incidence of cancers among workers who handle radioactive substances and among atomic-bomb survivors. The use of diagnostic radiology and radiotherapy has been increasing worldwide. One of the unique features of radiation used in medicine is the dosage range from a few milli-Gy, for most diagnostic examinations, to many tens of Gy, for the treatment of cancer. The radiation therapy for both benign and malignant disease appears to cause second cancers when substantial doses are administered to normal, healthy organs. The significant improvement in cancer treatment has resulted in longer survival and a growing number of high-dose-radiation-related second cancers. Second primary cancers have been emphasized as an important radiation-induced injury among the increasing numbers of cancer patients who have been cured by radiotherapy. Because of the paradoxical aspect of ionizing radiation in both helping to cure cancer and causing it, there is a need to provide information on radiation-induced cancer as well as the usefulness of radiation therapy to patients, relatives, and physicians in clinical practice. Epidemiologic investigations of people receiving medical radiation in the course of diagnosis or treatment have provided a great deal of information on the several levels of cancer risk following a broad spectrum of medical practices, and the data have been an important complement to the atomic-bomb survivor studies

To assess the effects of atomic bomb radiation on the incidence of multiple primary cancers (MPC), we analyzed the association between the incidence of second primary cancers in survivors of the atomic bombing of Nagasaki, and exposure distance. The incidence rate (IR) of a second primary cancer was calculated and stratified by the distance from the hypocenter and age at the time of bombing for the years 1968 through 1999. The IR of the first primary cancer was also calculated and compared with the second primary cancer to determine whether atomic bomb radiation was associated with the multiplicity of tumors. There were 511 confirmed cases of MPC in the 7572 cancer-bearing survivors. The crude IR was 27.6 per 100,000 person-years. The IR of second primaries decreased significantly with increasing distance from the hypocenter: relative risk, 0.89 per 1.0 km; 95% confidence interval, 0.84-0.94. A significant decrease was also noted for those of older ages at the time of the bombing, based on the attained age of the second primary cancer: relative risk, 0.91 per 1 year; 95% confidence interval, 0.90-0.92. These findings suggest that the radiation has affected the incidence of MPC. Furthermore, when compared with the first primary cancer, a stronger distance effect was suggested on the occurrence of a second primary cancer in the survivors. The present study suggests the significance of atomic bomb radiation on MPC in the survivors. These results on the incidence of MPC in the tumor-bearing survivors and its correlations with the atomic bombing of 62 years ago are described for the first time in this report., Cancer science, 99(1), pp.87-92; 2008

In the above-captioned paper [1], Scelo and colleagues present a pooled analysis of the occurrence of second primary cancers in nasopharyngeal carcinoma (NPC) patients from 13 cancer registries from Europe, Canada, Australia, and Singapore. This paper provides an important contribution as previous studies of second malignancies, following NPC, have been based on small sample sizes. However, there is a serious methodological issue arising from their study that needs to be discussed. Although the authors justifiably stratify the analysis, geographically into high risk (Singapore) and low risk (Europe, Canada, and Australia) areas, there is no mention in the paper of stratification by race or ethnicity.

e12592 Background: Disparities exist in breast cancer outcomes between specific racial/ethnic groups in the United States. Reasons for these disparities are multifactorial and include genetic diffe...

Five-year survival after invasive breast cancer is now at 90% and an estimated 2.97 million U.S. women are breast cancer survivors. The high incidence of invasive breast cancer, with over 220,000 U.S. women newly diagnosed every year, coupled with continued advances in survival has resulted in an ever increasing number of women at risk of developing a second primary cancer. Indeed, 41% of all second primary cancers diagnosed among U.S. women occur among breast cancer survivors and approximately 10% of breast cancer survivors will develop a second primary cancer. The four most common sites of second primary cancer, breast, lung, colon and endometrium, account for 70% of these second primaries. The appreciable risk of second primary cancer in breast cancer survivors is well-documented, yet relatively little is known about the etiologic and molecular determinants of these second primaries and little to no information on second primary cancer risk has been incorporated into preventive efforts and clinical care because of this evidence gap. This presentation will provide information on the following: 1. Descriptive epidemiology of second primary cancers among breast cancer survivors, 2. Review of the literature on risk factors for second primary breast cancer, and 3. Briefly describe the limited knowledge regarding risk factors for non-breast second primary breast cancers. Further studies of factors contributing to second primary cancers among breast cancer survivors can 1. Define the relationships between therapies for a first breast cancer and risk of these second cancers; 2. Clarify contributions of patient/clinical factors including modifiable exposures; and 3. Molecular profiling of first primary breast tumors aimed at distinguishing those at high vs. low risk of second primaries could advance approaches to risk stratification, tailored surveillance, treatment choice, and preventive interventions. Citation Format: Christopher I. Li. Second primary cancers among breast cancer survivors: Incidence and risk factors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES5-2.

It is now at least theoretically possible to prevent patients with hepatocellular carcinoma (HCC) from dying of HCC. Screening identifies small potentially curable lesions, and the diagnostic algorithm allows for efficient investigation and diagnosis. Radiofrequency ablation completely ablates more than 05% of lesions smaller than 2 cm. Second primary cancers can be dealt with in the same manner as the initial primary. If the management of HCC is so efficient and effective, liver transplantation may come to be used as a last resort, rather than the treatment of choice. This benefits patients with hepatitis C and other liver diseases because more organs become available for treatment of other liver diseases.

Summary In order to determine the efficacy and proper timing of routine PET scans for surveillance of recurrent head and neck squamous cell carcinoma (HNSCC), we evaluated the diagnostic performance of routine PET scans in relation to time interval from completion of treatment. Amongst 206 retrospectively evaluated post-treatment PET scans of 159 patients with HNSCC, 156 were performed for routine surveillance in subclinical cases. Diagnostic performance of PET scan and follow-up outcome were evaluated in relation to the time interval (2–6 months, 6–12 months, 12–24 months, and >24 months) of PET scan from the completion of treatment. Overall sensitivity and NPV of these PET scans for recurrence were 92.5% and 94.8%, compared with 55.0% and 76.9% for conventional evaluation methods. In the 156 routine scans, the diagnostic sensitivity, specificity, and NPV for locoregional recurrence were 90%, 91% and 97%, respectively, and the values for distant metastases and second primary cancers were 100%, 97% and 100%, respectively. The diagnostic accuracy of routine PET scans was not significantly altered by the time interval. Most (97%) of true negative cases on routine PET scans had no recurrence during a median 14 months follow-up. PET scan may be a useful tool in routine surveillance for detection of recurrence in subclinical patients. For routine surveillance, the initial PET scan should be performed within 6 months after completion of treatment and the proper timing of next routine PET scan for subclinical patient with initial negative PET result might be 1 year after initial PET scan.

Gastric cancer ranks as the fourth most common cancer and the second most frequent cause of cancer death worldwide.1 The aetiology includes causes such as Helicobacter pylori infection (for distal gastric cancer but not for cardia cancer),2 dietary imbalance, smoking, and genetic factors.2,3 Estimation of the incidence of second primary cancers may provide valuable insight into the aetiology and shared risk factors with the initial cancer. However, as gastric cancer patients have poor survival,4 a study of second malignancies after primary gastric cancer may not be informative. Instead, we examined the occurrence of second gastric cancers following any first cancers, based on the nationwide Swedish Family Cancer Database. This database has been described in detail previously.5 Briefly, it was created by linking information from the Multigenerational Register, censuses, Cancer Registry, and death …

The purpose of this study is to estimate the risk of second primary cancer (SPC) in 129 consecutive patients with splenic marginal zone lymphoma (SMZL) diagnosed in three Italian haematological centres. The person-years method deriving as a sum of products of age- and sex- specific rates and of the corresponding time at risk was used. The SPC Standardized Incidence Ratio (SIR) was 2.03 with a 95% confidence interval: [1.05, 3.56] (p < 0.05) and the corresponding Absolute Excess Risk (AER) was 145.8 (per 10000 SMZL patients per year). Our findings evidence a high frequency of additional cancers in patients with SMZL and suggest that the incidence rate of SPCs is significantly different from that expected in the general population.

It may be useful to look at the risk patterns for developing a second primary malignancy after a first primary melanoma diagnosis in order to understand the etiology and mortality due to melanoma. In this volume, W.B. Grant has proposed the interesting hypothesis that solar UV radiation and smoking may be inversely associated with the development of melanoma through the presence of dermal or solar elastosis. However, this association is inconsistent and may be explained by confounding by outdoor activity, physical exercise, obesity, diet and underlying immune or genetic factors.

516 Background: Second primary cancers are a major concern for young adult colorectal cancer (CRC) survivors. The impact of treatment with radiation on the risk for second solid and hematological malignancies, as well as the typical latency period before development of a second cancer, requires elucidation. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect CRC cases in young adults (aged 20-40 years) diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The latency exclusion period from the date of diagnosis was 5 years. We investigated the possible effect of radiation therapy on risk for a second cancer, and established the typical latency period after initial diagnosis (5-10 years and >10 years). Results: A total of 9,537 cases of CRC in young adults were available for analysis. Radiation was administered in 1,823 (19.1%) patients. Second primary cancers occurred in 798 cases, 754 (94.5%) solid tumors and 44 (5.5%) hematological malignancies respectively. In the latency period 5-10 years after initial diagnosis, “All Solid Tumors” (SIR: 1.85, p10 years after initial diagnosis, an increased risk of developing pancreatic cancer (SIR: 1.90, p10 years latency periods. Pancreatic cancer risk was increased specifically in the >10 years latency period. Radiation treatment did not pose an increased risk for any specific second primary cancers. Interestingly, young adult CRC survivors did not have an increased risk for hematological malignancies compared to the general population.

e20522 Background: The prevalence of multiple primary malignancies at any age ranges from 0.73% to 11.7%. Since the population is getting older and survival improves in many adult malignancies, the...

We studied second primary cancer among 25,947 patients diagnosed with squamous cell carcinoma of the skin (SCC) in Sweden between 1958 and 1992. In total, 5,706 patients developed a second primary cancer at any site, compared with an expected number of 2,651 [standardized incidence ratio (SIR) = 2.15; 95% confidence interval (CI) = 2.10-2.21]. Men below 60 years of age at diagnosis of SCC had higher SIR (2.5; CI = 2.2-2.8) with the highest risk during the first year of follow-up (SIR = 9.2; CI = 6.9-12.2). If second primary SCC was excluded, the SIR was reduced to 1.30 (CI = 1.25-1.34); the relationships by sex, age and time since diagnosis remained similar. For skin cancer, the SIR for second SCC was markedly elevated (SIR = 15.6) and the risk of malignant melanoma was elevated 3-fold. Significantly increased risks were found for most second cancers in squamous cell epithelium: lip (SIR = 5.2), respiratory organs (SIR = 1.7), esophagus (SIR = 1.5), cervix uteri (SIR = 2.2), and vulva including vagina (SIR = 2.3). There was a generally increased risk of almost 2-fold for second cancer in hematopoietic or lymphoproliferative tissues. Slightly increased rates (SIR = 1.0-1.5) were seen for second tumors in digestive tissues. Finally, a high SIR (SIR = 5.5) was observed for second primary cancer in salivary glands. In conclusion, patients with SCC are at increased risk to develop new primary cancer, especially in skin, squamous cell epithelial and tobacco-related tissues. Common risk factors among the tumor types might explain our findings, however, an intrinsic susceptibility among SCC patients to develop cancer is also possible.

1589 Background: The incidence of SPLC in Germany was reported to be 1.2 per 100,000 inhabitants in 2007 and the prevalence of second primary cancers reported by the US International Cancer Institute's Surveillance, Epidemiology and End Results Program has more than doubled over the last 25 years. Recently there has been tremendous progress in the ability to detect driver mutations in lung cancer and large studies presented the frequencies of driver mutations in unselected patient populations. We conducted an association study of known genetic driver events and clinical characteristics with the occurence of SPLC. Methods: Within the Network Genomic Medicine Lung Cancer, a local molecular screening network encompassing hospitals and office-based oncologists in the catchment area of the Center for Integrated Oncology Köln Bonn, we retrospectively reviewed the medical records of 375 molecularly annotated NSCLC patients for their SPLC status and clinical characteristics (age at diagnosis, histology, sex, smoking status). Molecular analysis for lung adenocarcinoma included the EGFR, ALK, BRAF, KRAS and PIK3CA status and for squamous cell lung cancer the FGFR1 and PIK3CA status. Results: 84 of 375 (22,4%) patients were SPLCs. The median age of SPLC diagnosis was 70 yrs. (Range 53 - 85 yrs.) and differed significantly from the rest of the population with a median age of 65 yrs. (Range 28 - 86 yrs.). The frequency of SPLCs was not significantly different between males and females (p = 0,259). In univariate logistic regression analysis active and former smoking, positive PIK3CA mutation and FGFR1 amplification status as well as age were significantly associated with the occurrence of SPLC. In a multivariate logistic regression analysis including the variables mentioned above only PIK3CA mutations (OR 9,48 95% CI 1,83 - 49,1) (p = 0,007) and age (OR 1,06 95% CI 1,03 - 1,1) (p = 0,015) could be confirmed to be independent prognosticators for the occurrence of SPLCs. Conclusions: The occurrence of SPLC was associated with age and PIK3CA mutations in our study population. Further comprehensive investigations on this topic are needed to confirm our findings and to further understand the association between mutation status and SPLCs.

3578 Background: The risk of second primary colorectal cancers among rectal cancer patients has been described, but little is known about the risk of non-colorectal malignancies that may occur in the field of radiation. We attempted to quantify the risk, using data from the large population-based California Cancer Registry (CCR). Methods: We analyzed the CCR data for surgically-treated locoregional rectal cancer cases, diagnosed during the period 1988–2009. We excluded cases with second primary tumor (SPT) diagnosed within 12 months of initial diagnosis . Radiation treatment used was external beam radiation therapy. Standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated to evaluate risk as compared to the underlying population after matching for age, sex, ethnicity, and time. Results: Of the study cohort of 13,418 rectal cancer cases, 1572 cases of SPTs were observed . The SIR was increased for small intestine cancer among cases receiving radiation treatment (4 cases observed vs. 1.01 cases expected; SIR=3.94, 95% CI 1.07-10.10) but not among cases lacking radiation treatment (4 observed vs. 4.45 expected; SIR=0.90, 5% CI 0.24-2.30). Among females treated with radiation, the SIR was increased for uterine cancer (12 observed vs. 5.59 expected; SIR=2.15, 95% CI 1.11 to 3.75) but not among cases lacking radiation therapy (23 observed vs. 26.17 expected; SIR=0.88, 95% CI 0.56-1.32). Among males receiving radiation treatment, the SIR for prostate cancer was decreased (23 observed vs. 69.78 expected; SIR=0.33; 95% CI 0.21 to 0.49) but of borderline significance among males lacking radiation therapy (243 observed vs. 276.97 expected; SIR=0.88, 95% CI 0.77-0.99). No significant differences were observed for cancers of the vagina, cervix, ovary, kidney, bladder, penis, testes, or leukemia based on prior radiation treatment for rectal cancer. Conclusions: Patients receiving pelvic radiation for treatment of rectal cancer have a subsequently higher than expected incidence of small intestine and uterine cancer. The incidence of prostate cancer appears to fall after pelvic radiation. These unexpected findings suggest complex relationships associated with radiation treatment for rectal cancer and SPT risk.

The occurrence of second primary cancers was explored in patients with squamous cell cancer of the skin (SCC). The excess incidence subsequent to SCC was mainly in cancers related to sunlight and smoking, and in lymphoproliferative malignancies, it was largest (10-fold) in salivary gland cancer.

327 Background: Development of second primary cancers among gastrointestinal stromal tumor (GIST) patients is not very well studied. This study was conducted to evaluate second primary malignancies in GIST patients using U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry database. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER Stat) database: Incidence - SEER 13 Regs Research Data, Nov 2011 Sub, Vintage 2009 Pops (1992-2009) using MP-SIR session. We analysed secondary cancer rate among adult GIST patients during the period 1992-2009. We also compared the risk of secondary malignancies in pre- (1992-2001) to post-imatinib (2002-2009) eras. We used SEER MP-SIR session and Graph pad scientific software to calculate p value. Results: There were 2,436 (693 in pre-imatinib era and 1,743 in post-imatinib era) GIST patients reported during 1992-2009 period in SEER database. Among them, 163 GIST patients developed second primary malignancy, which is significantly higher than expected in general population, with observed/expected (O/E) ratio: 1.31, p value =

A precursor or latent stage of cancer is well known [1]. Chemoprevention aims either to block the initiation of cancer or else to arrest or reverse further progression during the precursor phase. Thus, Vitamin A analogues (retinoids) have been shown to arrest or reverse the progression of leukoplakia in the mouth [2, 3], to reduce the occurrence of second primary cancers of the aero-digestive tract [4, 5] and to reduce, in association with vitamin E and selenium, mortality from gastric cancer in the Chinese population [6]. Similar too, is the ability of Tamoxifen to reduce the occurrence of second primary breast cancers in women at high risk [7].

This study was conducted to examine the incidence rates and cumulative risks of second primary cancers in Osaka and to compare the observed number of second primary cancers with the expected number calculated using cancer incidence rates among Osaka residents. Study subjects were all reported cases aged 0–79 who were first diagnosed as having a first primary cancer between 1966–86. Incidence of second primary cancer among the study subjects was examined through to the end of 1989. The total number of study subjects was 217,307. During the follow-up period (mean duration: 3.7 years), second primary cancers developed in 5,071 patients (2.3%). Incidence of synchronous (interval

e12009 Background: One of the most serious events experienced by cancer survivors is the diagnosis of a new cancer. The number of patients with second cancers is growing rapidly, comprising about 1...

377 Background: To study the overall and site specific risk and prognostic significance of second primary cancers (SPC) in patients diagnosed with renal cell carcinoma (RCC). Methods: The Surveillance Epidemiology and End Results (SEER) database was queried for all patients with RCC as the first cancer and one or more SPC (1973-2006). SPC diagnosed within 1 month of diagnosis of RCC or at autopsy/death were excluded. Deidentified information was obtained to analyze the effect of SPC on overall survival (OS) of RCC patients. Results: A total of 3,795 patients with RCC and ≥ 1 SPC were identified. The ratio of observed/expected cases (O/E ratio) of RCC and ≥ 1 SPCs was 1.18 (95% C.I. 1.15-1.22), significantly greater than the general population (p Conclusions: Our comprehensive analysis of SPCs in patients with RCC as the first primary malignancy using SEER data suggests that about 10% of RCC patients develop SPC and that several patient, tumor and treatment-related factors affect the risk of SPC at specific sites. Further, SPC can adversely influence the prognosis of patients with RCC, especially those >60 years old, receiving radiation or diagnosed with a SPC within 1 year after RCC diagnosis. These results may have significance in planning surveillance strategies to improve the survival of patients with RCC. No significant financial relationships to disclose.