Subsequent Cancers Research Articles

Familial Risks Between Urolithiasis and Cancer

Urolithiasis (UL, urinary tract stone disease) has been reported to increase subsequent cancers in the urinary tract. Recently, we showed data that surveillance bias may be an important confounder in the reported associations. In the present approach we want to address the question of possible cancer risk posed by UL mechanistically. Both UL and cancer have strong genetic components and we hypothesize that familial association between UL and cancer may be plausible. We thus assess familial risks between UL and cancer, hoping to find an explanation why UL may pose a risk of cancer. UL patients were identified from hospital inpatient and outpatient records and they were organized in families based on the Multigeneration Register into which also national cancer data were linked. Standardized incidence ratios were calculated for cancer in the offspring generation when parents were diagnosed with UL, and conversely for UL when parents were diagnosed with cancer. Familial risks between UL and cancer were generally small and inconsistent providing no convincing support of genetic sharing between UL and cancer. However, bladder UL was associated weakly with prostate cancer, and ureter and bladder UL were associated with salivary gland cancer. Potential mechanisms for these findings are proposed.

A comparison of five methods of measuring mammographic density: a case-control study

BackgroundHigh mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening.MethodsWomen participating in the “Predicting Risk Of Cancer At Screening” (PROCAS) study, a study of cancer risk, completed questionnaires to provide personal information to enable computation of the Tyrer-Cuzick risk score. Mammographic density was assessed by visual analogue scale (VAS), thresholding (Cumulus) and fully-automated methods (Densitas, Quantra, Volpara) in contralateral breasts of 366 women with unilateral breast cancer (cases) detected at screening on entry to the study (Cumulus 311/366) and in 338 women with cancer detected subsequently. Three controls per case were matched using age, body mass index category, hormone replacement therapy use and menopausal status. Odds ratios (OR) between the highest and lowest quintile, based on the density distribution in controls, for each density measure were estimated by conditional logistic regression, adjusting for classic risk factors.ResultsThe strongest predictor of screen-detected cancer at study entry was VAS, OR 4.37 (95% CI 2.72–7.03) in the highest vs lowest quintile of percent density after adjustment for classical risk factors. Volpara, Densitas and Cumulus gave ORs for the highest vs lowest quintile of 2.42 (95% CI 1.56–3.78), 2.17 (95% CI 1.41–3.33) and 2.12 (95% CI 1.30–3.45), respectively. Quantra was not significantly associated with breast cancer (OR 1.02, 95% CI 0.67–1.54). Similar results were found for subsequent cancers, with ORs of 4.48 (95% CI 2.79–7.18), 2.87 (95% CI 1.77–4.64) and 2.34 (95% CI 1.50–3.68) in highest vs lowest quintiles of VAS, Volpara and Densitas, respectively. Quantra gave an OR in the highest vs lowest quintile of 1.32 (95% CI 0.85–2.05).ConclusionsVisual density assessment demonstrated a strong relationship with cancer, despite known inter-observer variability; however, it is impractical for population-based screening. Percentage density measured by Volpara and Densitas also had a strong association with breast cancer risk, amongst the automated measures evaluated, providing practical automated methods for risk stratification.

Association of Treatment for Hodgkin Lymphoma With Estrogen Receptor Status of Subsequent Breast Cancers

This population-based cohort study examines the association of radiotherapy for Hodgkin lymphoma with risk of ER-positive and ER-negative breast cancers using data from the US National Cancer Institute Surveillance, Epidemiology, and End Results database.

Subsequent nonmelanoma skin cancers and impact of immunosuppression in liver transplant recipients.

Nonmelanoma skin cancers (NMSCs) are the most frequent cancers in solid organ transplant recipients, with a high rate of subsequent tumors. To describe subsequent NMSCs in a large cohort of liver transplantrecipients (LTRs) with long follow-up and analyze the factors influencing it, including immunosuppressive regimen. A total of 96 LTRs (76 male) with a personal post-transplant history of squamous cell carcinoma, basal cell carcinoma or Bowen's disease were included, with a median follow-up of 12.4years (range, 1.5-27.8) after liver transplantation. The median follow-up after first NMSC was 6.4years (range, 0.17-22.1). In all, 52 patients (53.1%) developed 141 subsequent NMSCs with a basal cell carcinoma-to-squamous cell carcinoma ratio of 1.8:1. The actuarial risk for development of a second NMSC was 13.7% at 1year, 28.4% at 2years, 49.4% at 5years, 65.7% at 10years, and 88.4% at 15years. Multivariate analysis found that skin phototype I or II (vs III or IV) was a significant risk factor for development of a second NMSC (hazard ratio, 2.556; 95% confidence interval, 1.45-4.48; P=.001), whereas withdrawal of calcineurin inhibitors was significantly protective (hazard ratio, 0.358; 95% confidence interval, 0.142-0.902; P=.029). Retrospective analysis. Subsequent NMSCs are very frequent in LTRs, and conversion from a calcineurin inhibitor-based immunosuppressive regimen to a mammalian target of rapamycin inhibitor/antimetabolite-based immunosuppressive regimen can reduce subsequent NMSCs.

Epidemiology of gliomas in women diagnosed with breast cancer supports the protective role of estrogenic exposure

Gliomas represent the most common type of brain cancers, but their etiology is still poorly understood and understanding of their risk factors is limited. The role of sex hormones in the development of brain cancers has been suggested by epidemiological and experimental studies and clinical observations, which highlighted the need for more evidence before hormone-modulating interventions are developed for prevention or treatment of gliomas. The results of this retrospective cohort study using data from SEER 9 cancer registries demonstrate a decreased risk of brain cancers in women diagnosed with breast cancers at 40+ years, which is consistent with hypothesis that estrogenic exposure reduces the risk of development of gliomas. In contrast, women diagnosed with breast cancer at < 40 years display an increased risk of subsequent brain cancers than women in general population, which likely reflects the role of shared genetic risk factors. These findings support the protective role of estrogens against development of gliomas and suggest the importance of early diagnosis and development of preventive approaches for women diagnosed at younger age (Tab. 2, Fig. 1, Ref. 37).

Risks of different skin tumour combinations after a first melanoma, squamous cell carcinoma and basal cell carcinoma in Dutch population-based cohorts: 1989-2009.

Skin cancer patients are primarily at increased risk of developing subsequent skin cancers of the same type. Shared risk factors might also increase the occurrence of a different type of subsequent skin cancer. To investigate risks of different skin tumour combinations after a first melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). All melanoma and SCC patients included in the national Netherlands Cancer Registry (NCR) and all BCC patients included in the regional Eindhoven Cancer Registry (ECR) between 1989 and 2009 were followed until diagnosis of a subsequent different skin cancer (melanoma, SCC or BCC), date of death or end of study. Cumulative risks, standardized incidence ratios (SIR) and absolute excess risks (AER) of subsequent skin cancers were calculated. A total of 50 510 melanoma patients and 64 054 patients with a SCC of the skin were included (national data NCR). The regional data of the ECR consisted of 5776 melanoma patients, 5749 SCC patients and 41 485 BCC patients. The 21-year cumulative risk for a subsequent melanoma after a first SCC or BCC was respectively 1.7% and 1.3% for males and 1.3% and 1.2% for females; SCC after melanoma or BCC was 4.6% and 9.3% (males) and 2.6% and 4.1% (females); BCC after melanoma or SCC was respectively 13.2% and 27.8% (males) and 14.9% and 21.1% (females). SIRs and AERs remained elevated up to 21 years after the first melanoma, SCC or BCC. This large population-based study investigating risks of developing a different subsequent cutaneous malignancy showed high-cumulative risks of mainly KC and markedly increased relative and absolute risks of all tumour combinations. These estimates confirm a common carcinogenesis and can serve as a base for follow-up guidelines and patient education aiming for an early detection of the subsequent cancers.

Risk of Subsequent Bone Cancers Among 69 460 Five-Year Survivors of Childhood and Adolescent Cancer in Europe.

We investigate the risks of subsequent primary bone cancers after childhood and adolescent cancer in 12 European countries. For the first time, we satisfactorily address the risks beyond 40 years from diagnosis and beyond 40 years of age among all survivors. This largest-ever assembled cohort comprises 69 460 five-year survivors of cancer diagnosed before age 20 years. Standardized incidence ratios, absolute excess risks, and multivariable-adjusted relative risks and relative excess risks were calculated. All statistical tests were two-sided. Overall, survivors were 21.65 times (95% confidence interval = 18.97 to 24.60 times) more likely to be diagnosed with a subsequent primary bone cancer than expected from the general population. The greatest excess numbers of bone cancers were observed after retinoblastoma, bone sarcoma, and soft tissue sarcoma. The excess number of bone cancers declined linearly with both years since diagnosis and attained age (all P < .05). Beyond 40 years from diagnosis and age 40 years, there were at most 0.45 excess bone cancers among all survivors per 10 000 person-years at risk; beyond 30 years from diagnosis and age 30 years, there were at most 5.02 excess bone cancers after each of retinoblastoma, bone sarcoma, and soft tissue sarcoma, per 10 000 person-years at risk. For all survivors combined and the cancer groups with the greatest excess number of bone cancers, the excess numbers observed declined with both age and years from diagnosis. These results provide novel, reliable, and unbiased information about risks and risk factors among long-term survivors of childhood and adolescent cancer.

The characteristics of breast cancer patients with metachronous primary malignancies

Introduction. The risk of developing subsequent primary cancers varies from 1% to 18% and it depends on the type of first cancer and treatment methods applied. Considering the time of occurrence, multiple primary cancers generally fall into two categories: synchronous and metachronous. In breast cancer patients, 10.5% developed multiple primary cancers, from which 23.8% had synchronous, 79% had metachronous and the remaining 2.8% had both synchronous and metachronous malignancies. In patients with breast cancer, elevated risk is observed especially in the development of contralateral breast cancer, endometrial cancer, esophageal cancer, ovarian cancer and thyroid cancer. Aim. This paper presented the characteristics of breast cancer patients with metachronous primary malignancies in relation to the type of metachronous primaries (breast versus non-breast) and to analyse the impact of the type of metachronous cancers on survival rate. Material and methods. Among patients treated for breast cancer between 1963 and 2010, 354 patients (2.1%) developed metachronous primary malignancies and these made up 13.8% of all patients with multiple primary cancers. The mean age at diagnosis of the first breast cancer was 53 ± 11.5 years; positive family cancer history was noted in 127 patients (35.9%). Metachronous malignancies are defined as primaries following the diagnosis of breast cancer in a time interval greater than or equal to than 6 months. In our group, the mean time interval between the diagnosis of breast cancer and the appearance of metachronous malignancies was 100.9 ± 74.9 months (range: 6–543 months, median: 83 months). For comparison of the two groups (patients with second breast vs non-breast cancer) we used the Pearson’s Chi-square test for independence (for categorized variables) and variance analysis with Student’s t-test (for continuous variables). The survival rate was evaluated with the Kaplan-Meier method, and the log rank test was applied to assess the influ­ence of some factors on the evaluated results. The significance level at α = 0.05 was adopted for all statistical analyses. Results. The probability of occurrence of new cancer averaged from 38.1% to 67.8% for 5 and 10 years after diagnosis of first breast cancer, respectively. In our group, 380 cases of metachronous carcinomas were noted in 354 analysed patients. The most frequent metachronous malignancy was breast cancer (194 cases — 54.8%), which occurred as second (192 cases) or third (2 cases) cancer. Patients with contralateral breast cancer in comparison to other types of metachronous malignancies were significantly (p &lt; 0.05): younger (under 50 years: 56.2% vs 34.4%), premenopausal (69.6% vs 48.8%), had a lobular type of first breast cancer (6.7% vs 1.3%), and rarely received tamoxifen (25.3% vs 48.2%). The type of me­tachronous cancers significantly influenced survival rate: 10-year overall survival rates were 80.1% vs 67.8%, (p = 0.0271). Conclusions. The risk of occurrence of second malignancies in breast cancer survivors makes early detection of metachronous malignancies obligatory because it is an important factor which influences the quality of life in breast cancer survivors.

High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer

BackgroundAlthough high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active.MethodsWe used polymerase chain reaction (PCR) to identify HPVs in specimens from 52 Australian men with benign prostate biopsies who 1 to 10 years later developed prostate cancer. Immunohistochemistry (IHC) was used to assess the expression of HPV E7 oncoproteins, cytokeratin and prostate specific antigen (PSA).We used RNASeq data from The Cancer Genome Atlas (TCGA) to identify possible HPV RNA sequences in prostate cancer.ResultsHPV screening using standard PCR was conducted on 28 of the 52 sets of benign and later prostate cancers. HPV L1 genes were identified in 13 (46%) benign and 8 (29%) of 28 later prostate cancers in the same patients. HPV E7 genes were identified in 23 (82%) benign and 19 (68%) of 28 subsequent prostate cancers in the same patients. The same HPV types were present in both the benign and subsequent prostate cancers in 9 sets of specimens. HPV type 16 was identified in 15% of benign and 3% of prostate cancers. HPV type 18 was identified in 26% of benign and 16% of prostate cancers. Small numbers of HPV types 45, 47, 76 and 115 were also identified.High confidence RNA-Seq evidence for high risk HPV types 16 and 18 was identified in 12 (2%) of the 502 TCGA prostate cancer transcriptomes.High risk HPV E7 oncoprotein was positively expressed in 23 (82%) of 28 benign prostate specimens but only in 8 (29%) of 28 of the later prostate cancer specimens. This difference is statistically significant (p = 0.001). Prostate specific antigen (PSA) was more highly expressed in 26 (50%) of 52 prostate cancer specimens as compared to prior benign prostate specimens in the same patients.ConclusionsHigh risk HPVs are present in benign prostate tissues prior to the development of HPV positive prostate cancer. There is a significantly higher expression of HPV E7 oncoproteins in benign prostate tissues as compared to late prostate cancer that subsequently developed in the same patients. This observation suggests that HPV oncogenic activity is an early phenomenon in a majority of prostate oncogenesis. TCGA RNA-Seq data suggests that HPV is biologically active in some prostate tumour samples.

Therapy-Related Clonal Hematopoiesis in Patients with Non-hematologic Cancers Is Common and Associated with Adverse Clinical Outcomes

Clonal hematopoiesis (CH), as evidenced by recurrent somatic mutations in leukemia-associated genes, commonly occurs among aging human hematopoietic stem cells. We analyzed deep-coverage, targeted, next-generation sequencing (NGS) data of paired tumor and blood samples from 8,810 individuals to assess the frequency and clinical relevance of CH in patients with non-hematologic malignancies. We identified CH in 25% of cancer patients, with 4.5% harboring presumptive leukemia driver mutations (CH-PD). CH was associated with increased age, prior radiation therapy, and tobacco use. PPM1D and TP53 mutations were associated with prior exposure to chemotherapy. CH and CH-PD led to an increased incidence of subsequent hematologic cancers, and CH-PD was associated with shorter patient survival. These data suggest that CH occurs in an age-dependent manner and that specific perturbations can enhance fitness of clonal hematopoietic stem cells, which can impact outcome through progression to hematologic malignancies and through cell-non-autonomous effects on solid tumor biology.

Surveillance after surgical resection of stage I non-small cell lung cancer

Surgical resection is the mainstay of treatment for stage I non-small cell lung cancer (NSCLC), with reported 5-year overall survival rates as high as 90% (1). Despite this successful treatment, NSCLC remains the leading cause of cancer death worldwide (2), partly because of its high recurrence rates and the elevated risk of developing subsequent new primary lung cancers. Recent data has demonstrated that surveillance after early lung cancer resection is not a futile exercise, since many patients can be diagnosed with new or recurrent cancer, and can be treated accordingly with high survival rates (3). In this article, we present an overview of guidelines and recent evidence surrounding the optimal surveillance regimen and follow-up care for survivors of stage I NSCLC.

Quality indicators for screening colonoscopies and colonoscopist performance and the subsequent risk of interval bowel cancer: a systematic review protocol.

The objective of this systematic review is to assess the association between quality indicators related to the individual colonoscopist's performance and subsequent interval cancers in patients participating in bowel cancer screening programs, following the JBI approach.This systematic review of association will search all relevant literature on the subject to answer the following review questions.

Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database

BackgroundMost patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited...

The burdens of lung cancer involved multiple primary cancers and its occurring patterns\u2013SEER Analysis between 1973 and 2006

The prognosis of malignancies has improved in recent years, subsequent primary cancers (SPCs) have become more frequent. This study investigates the patterns of lung cancer involved multiple primary cancers. We enrolled 206,619 primary lung cancer patients and 2,071,922 patients with other primary malignancies from Surveillance, Epidemiology and End Results (SEER) database. Observed annual risk (OAR) and absolute numbers were used to describe the risk of SPC and observed cases of SPC per 10,000 person-years at risk. Overall, OAR of SPCs following lung cancer was 176.28. At follow-up, 41.26% of SPCs occurred within 12–59 months while the highest OAR appeared after 120 months. The overall OAR of subsequent lung cancer after other malignancies was 27.90. Overall, the highest OAR and the highest absolute numbers of subsequent lung cancers were noticed 60–119 months and over 120 months post-diagnosis, respectively. Ten related cancers were listed. Our findings encourage surveillance for 10 common SPCs in lung cancer survivors during follow-up as well as screening for lung cancer after 10 common malignancies.

Adolescent body mass index and risk of colon and rectal cancer in a cohort of 1.79 million Israeli men and women: A population-based study.

This study examined the association between the body mass index (BMI) in late adolescence and the risk of colon and rectal cancer. This study analyzed a cohort of 1,087,358 Jewish men and 707,212 Jewish women who underwent health examinations at the ages of 16 to 19 years between 1967 and 2002 and were followed by linkage to the national cancer registry up to 2012. Cox regression was used to estimate hazard ratios (HRs) for cancer according to age- and sex-adjusted BMI percentiles from the US Centers for Disease Control and Prevention (overweight, 85th percentile to <95th percentile; obesity, ≥95th percentile). Over a median follow-up of 23 years, 2967 incidence cases of colorectal cancer, including 1977 among men (1403 in the colon and 574 in the rectum) and 990 among women (764 in the colon and 226 in the rectum), were identified. Overweight and obesity were associated with the risk for colon cancer among both men (HR for overweight, 1.53; 95% confidence interval [CI], 1.28-1.84; HR for obesity, 1.54; 95% CI, 1.15-2.06; statistically significant from a BMI of 23.4 kg/m2 [spline analysis]) and women (HR for overweight, 1.54; 95% CI, 1.22-1.93; HR for obesity, 1.51; 95% CI, 0.89-2.57; significant from a BMI of 23.6 kg/m2 ). Obesity, but not overweight, was associated with a risk for rectal cancer among men (HR, 1.71; 95% CI, 1.11-2.65; significant from a BMI of 29.6 kg/m2 ) and women (HR, 2.03; 95% CI, 0.90-4.58; significant from a BMI of 30.6 kg/m2 ). Being overweight or obese in adolescence was associated with an increased risk of subsequent colon cancers in men and women, whereas obesity was associated with rectal cancer. Cancer 2017;123:4022-30. © 2017 American Cancer Society.

Impact of liver transplantation on the risk of second malignant tumors among hepatocellular carcinoma patients

ABSTRACTBackground: Population-based data on the development of second malignant neoplasms (SMNs) following the diagnosis of hepatocellular carcinoma (HCC) are uncommon. We evaluated this clinical vignette in HCC patients within the Surveillance, Epidemiology and End Results (SEER) database.Methods: The SEER database (1973–2012) was queried using the SEER*Stat program to determine the clinico-pathological features of HCC patients with more than one year survival who developed SMNs. Standardized incidence ratios (SIRs) were calculated to determine the risk of each type of subsequent cancers. Relative risk was assessed to determine the impact of liver transplantation on the development of second malignant neoplasms.Results: On SIR analysis, the following sites have an enhanced risk of developing an SMN following the diagnosis of HCC: tongue, anal canal, liver, lung, kidney, thyroid, non-Hodgkin lymphoma (both nodal and extra-nodal disease) and acute monocytic leukemia (P < 0.05 for all sites). A significantly higher RR was found for the development of lung cancer (RR = 2.096), thyroid cancer (RR = 3.045) and non-Hodgkin lymphoma (RR = 3.822) among patients who underwent liver transplantation compared to those who did not (P < 0.05).Conclusion: There is an excess risk for developing a number of SMNs among patients diagnosed with HCC.

Complex sclerosing lesions and radial sclerosing lesions on core needle biopsy: Low risk of carcinoma on excision in cases with clinical and imaging concordance

Complex or radial sclerosing lesions (CSL/RSL) are uncommon diagnoses on core needle biopsy with a reported upgrade rate ranging between 0% and 23%. As a result, their management remains controversial. In this study, we sought to determine the rate of malignancy on excision for patients with pure CSL/RSL on core biopsy, and to evaluate future breast cancer risk when CSL/RSL is managed without excision. We retrospectively reviewed 118 cases of CSL/RSL diagnosed on image-guided breast biopsies between 2005 and 2014 at our institution. Of 98 analyzed patients, 34 (35%) underwent excision and 64 (65%) were observed. Demographic and clinical variables between excision and observation groups were compared. In excised specimens, factors associated with upgrade to malignancy were evaluated. The median age at diagnosis was 49 years (range, 27-88 years). In the excision group, 3/34 cases were associated with malignancy, an overall upgrade rate of 9%. All malignant cases had core needle biopsies interpreted as discordant and were BIRADS 4B or more on imaging. In the observation group, at a median follow-up of 2.2 years, 3/64 (5%) patients developed ipsilateral cancers, all of which were distant from the index CSL/RSL. In our series, we report a 9% malignancy rate on excision of BIRADS >4C lesions characterized as CSL/RSL on core biopsy. In patients with concordant biopsies and BIRADS 4A or lower lesions who underwent observation, we found a low rate of subsequent ipsilateral cancers. Further studies are needed to confirm that for CSL/RSL in concordant core biopsies and BIRADS 4A or lower, nonpalpable lesions, observation may be a reasonable alternative to excision.

Utility of surveillance MRI in women with a personal history of breast cancer

PurposeTo determine the utility and rate of biopsy in women with a positive history of breast cancer screened with MRI. MethodsRetrospective review of 491 breast MRI screening examinations in women with a personal history of breast cancer. ResultsIn total, 107 biopsies were performed, an average of 0.09 biopsies per person year. The positive predictive value for biopsies prompted by MRI findings was 0.24 (95% C.I. 0.10–0.38). Eight of the nine subsequent cancers were initially identified on screening MRI alone. ConclusionSurveillance MRI in breast cancer survivors may increase detection of subsequent cancers while increasing rate of biopsy.

Subsequent thoracic cancers among patients diagnosed with lung cancer: a SEER database analysis

Background: Population-based data on the development of subsequent thoracic cancers following the initial diagnosis of lung cancer are scarce. We evaluated this clinical scenario in lung cancer patients registered within the Surveillance, Epidemiology and End Results (SEER) database.Methods: The SEER database (1988–2013) was queried using the SEER*Stat program to determine the clinico-pathological features of lung cancer patients who develop subsequent thoracic cancers as well as the characteristics of these subsequent cancers. Associations were ascertained with chi-squared tests and survival analysis was performed using Kaplan–Meier methods. Standardized incidence ratios (SIRs) were calculated to determine the risk of each type of subsequent cancer.Results: A total of 223,274 lung cancer patients were identified and included in the current study. In this cohort, 6387 patients developed subsequent thoracic cancers. The following were associated with a higher likelihood of second cancers: female gender, younger age, white race, adenocarcinoma histology, married, lower AJCC stage, earlier year of diagnosis and local treatment with surgery rather than radiotherapy (p < .0001 for all parameters). In the subset of patients with subsequent thoracic cancers, survival was best for patients with second primary breast cancer followed by patients with lung or esophageal cancer (p < .0001). SIR analyses showed an excess risk for the development of esophageal cancer and second primary lung cancer following an initial diagnosis of lung cancer. This risk persists regardless of gender or receipt of radiotherapy (p < .05 for all scenarios).Conclusion: There is an excess risk for the development of esophageal cancer and second primary lung cancer following an initial lung cancer diagnosis. This risk is present irrespective of gender or receipt of radiotherapy.

Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy.

Purpose Childhood cancer survivors (CCSs) are at increased risk for subsequent malignant neoplasms (SMNs). We evaluated the long-term risk of SMNs in a well-characterized cohort of 5-year CCSs, with a particular focus on individual chemotherapeutic agents and solid cancer risk. Methods The Dutch Childhood Cancer Oncology Group-Long-Term Effects After Childhood Cancer cohort includes 6,165 5-year CCSs diagnosed between 1963 and 2001 in the Netherlands. SMNs were identified by linkages with the Netherlands Cancer Registry, the Dutch Pathology Registry, and medical chart review. We calculated standardized incidence ratios, excess absolute risks, and cumulative incidences. Multivariable Cox proportional hazard regression analyses were used to evaluate treatment-associated risks for breast cancer, sarcoma, and all solid cancers. Results After a median follow-up of 20.7 years (range, 5.0 to 49.8 years) since first diagnosis, 291 SMNs were ascertained in 261 CCSs (standardized incidence ratio, 5.2; 95% CI, 4.6 to 5.8; excess absolute risk, 20.3/10,000 person-years). Cumulative SMN incidence at 25 years after first diagnosis was 3.9% (95% CI, 3.4% to 4.6%) and did not change noticeably among CCSs treated in the 1990s compared with those treated earlier. We found dose-dependent doxorubicin-related increased risks of all solid cancers ( Ptrend < .001) and breast cancer ( Ptrend < .001). The doxorubicin-breast cancer dose response was stronger in survivors of Li-Fraumeni syndrome-associated childhood cancers (leukemia, CNS, and non-Ewing sarcoma) versus survivors of other cancers ( Pdifference = .008). In addition, cyclophosphamide was found to increase sarcoma risk in a dose-dependent manner ( Ptrend = .01). Conclusion The results strongly suggest that doxorubicin exposure in CCSs increases the risk of subsequent solid cancers and breast cancer, whereas cyclophosphamide exposure increases the risk of subsequent sarcomas. These results may inform future childhood cancer treatment protocols and SMN surveillance guidelines for CCSs.