Incidence Of Second Primary Tumors Research Articles

Abstract PO4-11-08: Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020

Abstract Introduction: Breast cancer survivors live longer due to early detection programs and therapeutic advances. Staging and molecular classification are important for prognosis and treatment. At the same time these patients are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decade with early detection and prevention programs of other tumors lacking. This study aims to identify, characterize and associate breast cancers with second primary malignancies based on different variables. Methods: We identified 3487 females with a first primary breast cancer between 2010 and 2020 in medical records at University Hospital of A Coruña in Spain. Over a median follow-up of 8 years, one hundred patients (2,9%) develop second cancer. According National Cancer Institute, second primary tumor (SPT) was defined as an invasive primary cancer after a first primary cancer. In our case a breast carcinoma. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast carcinoma) which were diagnosed at least 12 months after primary breast tumor. We analyzed breast cancer subtype, family history and pathogenic genetic variants, tobacco use and second primary tumor type. Results: Several clinical characteristics were evaluated, including breast cancer stage, histological type and subtype. The incidence of breast cancer and SPT was increased with age with peaks in the 60’s and 70’s, respectively. Only 13% had SPT between 40-49 years. Approximately 10 women a year, in our study, developed second cancer. 52% of SPT patients had cancer family history. Pathogenic variant study was carried in 25% of women with SPT, 46% of them no mutation were found, but in 17% was detected a germline BRCA1 deleterious variant. Other pathogenic variants were founded: 4% in BRCA2, and 33% in others genes (CHEK2, MSH2, MSH6, PMS2, CDH1, FANC1 y SMAD4) Regards tobacco use, active smokers were 13% and 12% of women had been smoking years ago. Of these 13 active smokers, 10 develop lung cancer (77%) an 5 of former smokers (42%). Luminal subtype was the most common breast cancer (33% Luminal A, 34% Luminal B Her2 negative, 10% Luminal B Her2 positive, 4% Her2-enriched, 10% Triple negative and 3% carcinoma in situ with estrogen and progesterone expression) and stage I and II were most frequent (80%). The most usual second primary neoplasms were lung, colorectal and pancreatic carcinoma (21%, 17% and 7% respectively), and only 2% contralateral breast cancer, with an average of approximately 4 years between breast cancer and the SPT. In 11% of patients were found more than 2 tumors. At the time of the analysis, 73% of these patients are free of disease. In SPT study population few recurrences were described, 2 relapses of breast cancer and 9 of SPT. The median between breast cancer diagnosis and the SPT diagnosis was 54 months [0,7 – 129]. The median to relapse of breast cancer was 73 months [68 – 77]. The median between SPT diagnosis and relapse was 39,25 months [1 - 134]. STP recurrences were observed in colorectal and lung cancer, mainly. Data on recurrences and mutations were not significative. Conclusion: In our breast cancer population the incidence of second primary tumors is around 3% over a 10 – year period. The diagnosis of the SPT arises several years after breast cancer and generally has a worse prognosis. Elevated risks of second cancer among breast cancer survivors treated in recent decade suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed. It is mandatory make an effort and focusing in recommendations and advise about tobacco consumption, healthy lifestyle and adherence to Pap test and stool test in survivors. Citation Format: Guadalupe Rama, Maria-Eva Perez-Lopez, Silvia Antolin Novoa, Cristina Reboredo, Beatriz Alonso, Sofia Silva Diaz, Begoña Graña, Lourdes Calvo, Tomas Garcia-Caballero. Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-08.

Oncology: What You May Have Missed in 2023.

Advances in oncology treatment methods have improved outcomes and quality of life for patients with cancer. However, care of these patients can be complex, and the contribution of physicians from different specialties is crucial. This article highlights important publications from 2023 on topics across a wide spectrum relating to the management of oncology patients. The literature was screened for significant new evidence that is relevant to internal medicine specialists and subspecialists whose focus is not oncology. Two articles address the importance of social interventions targeting end-of-life care for low-income and minority patients and the well-being of caregivers. Two additional articles address screening considerations in patients at risk for colorectal and lung cancer. Two more articles address safe use of hormone-related therapies to treat symptoms of menopause and prevent disease recurrence or progression in patients diagnosed with noninvasive breast neoplasia. Finally, several articles were included on topics related to COVID-19 vaccination in patients with cancer, use of cannabinoids for cancer pain control, chronic autoimmune adverse effects related to use of immune checkpoint inhibitors, and the incidence of second primary neoplasms.

Long-term outcomes of young, node-negative, chemotherapy-naïve, triple-negative breast cancer patients according to BRCA1 status

BackgroundDue to the abundant usage of chemotherapy in young triple-negative breast cancer (TNBC) patients, the unbiased prognostic value of BRCA1-related biomarkers in this population remains unclear. In addition, whether BRCA1-related biomarkers modify the well-established prognostic value of stromal tumor-infiltrating lymphocytes (sTILs) is unknown. This study aimed to compare the outcomes of young, node-negative, chemotherapy-naïve TNBC patients according to BRCA1 status, taking sTILs into account.MethodsWe included 485 Dutch women diagnosed with node-negative TNBC under age 40 between 1989 and 2000. During this period, these women were considered low-risk and did not receive chemotherapy. BRCA1 status, including pathogenic germline BRCA1 mutation (gBRCA1m), somatic BRCA1 mutation (sBRCA1m), and tumor BRCA1 promoter methylation (BRCA1-PM), was assessed using DNA from formalin-fixed paraffin-embedded tissue. sTILs were assessed according to the international guideline. Patients’ outcomes were compared using Cox regression and competing risk models.ResultsAmong the 399 patients with BRCA1 status, 26.3% had a gBRCA1m, 5.3% had a sBRCA1m, 36.6% had tumor BRCA1-PM, and 31.8% had BRCA1-non-altered tumors. Compared to BRCA1-non-alteration, gBRCA1m was associated with worse overall survival (OS) from the fourth year after diagnosis (adjusted HR, 2.11; 95% CI, 1.18–3.75), and this association attenuated after adjustment for second primary tumors. Every 10% sTIL increment was associated with 16% higher OS (adjusted HR, 0.84; 95% CI, 0.78–0.90) in gBRCA1m, sBRCA1m, or BRCA1-non-altered patients and 31% higher OS in tumor BRCA1-PM patients. Among the 66 patients with tumor BRCA1-PM and ≥ 50% sTILs, we observed excellent 15-year OS (97.0%; 95% CI, 92.9–100%). Conversely, among the 61 patients with gBRCA1m and < 50% sTILs, we observed poor 15-year OS (50.8%; 95% CI, 39.7–65.0%). Furthermore, gBRCA1m was associated with higher (adjusted subdistribution HR, 4.04; 95% CI, 2.29–7.13) and tumor BRCA1-PM with lower (adjusted subdistribution HR, 0.42; 95% CI, 0.19–0.95) incidence of second primary tumors, compared to BRCA1-non-alteration.ConclusionsAlthough both gBRCA1m and tumor BRCA1-PM alter BRCA1 gene transcription, they are associated with different outcomes in young, node-negative, chemotherapy-naïve TNBC patients. By combining sTILs and BRCA1 status for risk classification, we were able to identify potential subgroups in this population to intensify and optimize adjuvant treatment.

Clinical and pathological features of second primary neoplasms arising in head and neck reconstructive skin flaps

The incidence of second primary neoplasms arising in the skin reconstructive flap (SNAF) is increasing because of the increase in head and neck flap reconstruction and cancer survival. Prognosis, optimal treatment, and their clinicopathological-genetic features are under debate and are difficult to diagnose. We retrospectively reviewed SNAFs based on a single center’s experience over 20 years. Medical records and specimens of 21 patients with SNAF who underwent biopsies between April 2000 and April 2020 at our institute were retrospectively analyzed. Definite squamous cell carcinoma and the remaining neoplastic lesions were subclassified as flap cancer (FC) and precancerous lesions (PLs), respectively. Immunohistochemical studies focused on p53 and p16. TP53 sequencing was conducted using next-generation sequencing. Seven and 14 patients had definite FC and PL, respectively. The mean number of biopsies/latency intervals was 2.0 times/114 months and 2.5 times/108 months for FC and PL, respectively. All lesions were grossly exophytic and accompanied by inflamed stroma. In FC and PL, the incidences of altered p53 types were 43% and 29%, respectively, and those of positive p16 stains were 57% and 64%, respectively. Mutation of TP53 in FC and PL were 17% and 29%, respectively. All except one patient with FC under long-term immunosuppressive therapy survived in this study. SNAFs are grossly exophytic tumors with an inflammatory background and show a relatively low altered p53 and TP53 rate and a high p16 positivity rate. They are slow-growing neoplasms with good prognoses. Diagnosis is often difficult; therefore, repeated or excisional biopsy of the lesion may be desirable.

Characteristics and survival analysis of breast cancer survivors with metachronous double primary cancers: a retrospective cohort study.

Breast cancer (BC) is the most frequently diagnosed malignancies in females, and its incidence has increased dramatically recently. Clinical studies have shown that BC patients are developing double primary cancers more frequently than by chance, and the prognosis has changed greatly. Previous articles rarely mentioned metachronous double primary cancers in BC survivors. Thus, further analysis of the clinical characteristics and survival differences may provide valuable information in BC survivors. In this study, we retrospectively analyzed 639 cases of double primary cancers in BC patients. Cox univariate and multivariate regression analyses of clinical factors of overall survival (OS) were performed in patients with double primary cancers when breast cancer was the primary tumor to assess the correlation between clinical factors and OS in these patients with double primary cancers. Among the double primary cancer patients, BC was the most frequent first primary cancer. In terms of numbers, thyroid cancer was the most common type of double primary cancer among BC survivors. Patients had a younger median age when BC occurred as the first primary cancer rather than the second primary cancer. The total mean time interval between the onset of double primary tumors was 70.8 months. With the exception of the thyroid and cervical cancer, the incidence of second primary tumors was <60% within 5 years. However, the incidence was >60% within 10 years. The mean OS of double primary cancer patients was 109.8 months. Additionally, patients who had thyroid cancer as their second primary cancer had the highest 5-year survival rate, followed by cervical, colon, and endometrial cancer, while patients who had lung cancer as their second primary cancer had the lowest 5-year survival rate. OS risk of BC survivors with second primary cancers was significantly associated with age, menopause status, family history, tumor size, lymph node metastasis, and human epidermal growth factor receptor 2 (HER2) status. The identification of double primary cancers in earlier stages could play a critical role in guidance and lead to better outcomes. A prolonged follow-up examination period for BC survivors is needed to provide better guidance and treatments.

Risk of Second Primary Malignancies After External Beam Radiotherapy for Thyroid Cancer.

To investigate the association between external beam radiotherapy (EBRT) and the incidence of second primary tumors in patients with thyroid cancer. Data were extracted from the Surveillance, Epidemiology, and End Results 9 database. The study cohort included patients diagnosed with thyroid cancer between 1973 and 2017. Risk factors for second primary malignancies were identified with Cox proportional hazards models. Propensity score-matched analyses were used to assess the association between EBRT and second primary malignancies. Out of 72,392 patients with thyroid cancer, 7,684 (10.6%) developed a subsequent primary malignancy. Propensity score-matched analysis demonstrated patients receiving EBRT were more likely to develop second primary malignancies [30-year cumulative incidence=35.3% (95% confidence interval (CI)=30.4-39.8% vs. 28.1% (95% CI=27.0-29.2%); hazard ratio=1.17 (95% CI=1.03-1.33)]. In patients with thyroid cancer, EBRT is associated with an increased incidence of second primary malignancies.

Second primary tumors in retinoblastoma survivors: a study of 7 Asian Indian patients.

To assess the incidence, types, and outcomes of second primary tumors (SPT) in cases of retinoblastoma (RB) from a referral Tertiary eye care center METHODS: Retrospective chart review of 7 cases RESULTS: All 7 (100%) cases had bilateral RB at presentation. The mean age at diagnosis of RB was 16months (median 7months; range 5-72months). Treatment of RB with intravenous chemotherapy was noted in 3 (43%) patients, 1 (14%) patient had received external beam radiotherapy (EBRT) to the orbit, 1 (14%) patient had received a combination of chemotherapy and orbital EBRT, while 4 (57%) patients had undergone primary enucleation of the worse eye and focal treatment of the better eye. The mean age at detection of SPT was 15years (median 8years; range 6-46years). The mean time interval between diagnosis of RB and SPT was 13years (median 7years; range 1-41years). The SPT's included osteosarcoma of long bone (n = 2), eyelid sebaceous gland carcinoma (n = 2), ventricular ependymoma (n = 1), orbital neuroblastoma (n = 1), and acute lymphoblastic leukemia (n = 1). All patients received treatment for the SPT with either surgical excision (n = 2), intravenous chemotherapy (n = 1), or a combination of surgery/chemotherapy/radiotherapy (n = 4). Over a mean follow-up period of 8years (median 8years; range 4-11years), one (14%) patient died, while other 6 (86%) patients are alive and well. Though the incidence of SPT's in cases of RB is rare, life-long follow-up is mandatory in at-risk patients.

Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis.

As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P=0.01) and longer OS of ≥21 years (P<0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P<0.01). Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

Update of NGS analysis of Italian survey of second tumors in patients with diagnosis of GIST (gastrointestinal stromal tumor).

e23518 Background: In patients with GIST, literature reports a risk of second primary tumors between 4.5% and 33% with different distribution in the worldwide. The network of 7 italian EURACAN centers has collected clinical and molecular features of GIST patients with second primary tumors. Methods: We reviewed the clinical characteristics of 201 patients with GIST and second primary tumors in order to evaluate association between risk of dead and each possible factor, using Kaplan meier curve, log-rank test and Cox model for Hazard Ratio and it’s interval Confidence 95% estimation. Furthermore, NGS analysis ( 56 gene onco panel) in 72 patients with GIST was performed. Results: On the basis of the significant correlation previously observed between the Miettinen risk criteria of GIST (low/very low) and the incidence of second primary tumors (gastrointestinal tumors),P &lt; 0.001 (Abstr 11032 ASCO 2019), we observed in these patients a median age of diagnosis of GIST of 68, with prevalent gastric site localization ( KIT exon 11 mutation), NF1 and Lynch (kit/pdgfra WT) syndromes in the low risk subgroup. The more frequent site of second epithelial tumor in gastrointestinal tract was the colon followed by gastric, pancreatic and biliary tract. In patients with GIST with low-very low risk according Miettinen classification, after a median follow-up period of 25 years, we have observed that the gastroenteric site of second tumors occurrence is significantly related to the survival (p &lt; .0003). In the NGS analysis of the GIST we observed the pathogenetic somatic mutations in the following genes: BRCA 2 (p.Thr2125fs), but germline test negative, TP53 (p.Arg192*,p.Gly244Ser,p.His168Leu), RET (p.Lys120Asn, p.His168Leu, p.Thr930Met ), NRAS (p.Gly134Asp), CTNNB1 (p.Ser45Phe), MSH6 (P.Ala164Val), SMARCB1 (p.Arg192), VHL (p.Gly93Val), PTEN(p.Val158Ile, p.Asn323fs), STK1I (p.Arg40Cys), SMO (p.Glu194Lys), EGFR (p.Gly721Asp), ATM (p.Asp2708Asn), ERBB4 (p.Asn181Ile). Conclusions: In our analysis patients with GIST (low-very low classes according to Miettinen) have significant risk to death because of second primary tumors in gastrointestinal tract. Specific attention to gastrointestinal screening during the follow-up of GIST (low and very low risk) is required.

Relative and absolute risk of second primary neoplasms of the central nervous system.

1593 Background: Cranial radiation is known to increase the relative risk for developing a second primary neoplasm, but existing analyses do not take into account differential survival or follow-up. The absolute risk, or true incidence, of developing a second primary neoplasm in the central nervous system (CNS) is not well characterized. Methods: Patients diagnosed with cancer from between 1976 and 2016 were sampled using the Surveillance, Epidemiology, and End Results (SEER) Program. Relative risks were estimated using standardized incidence ratios (SIRs) and absolute risks were estimated using cumulative incidence (CI) functions with death as a competing risk. Among CNS primaries, comparison groups were matched by age, sex, year of diagnosis, primary histology, and lesion location. Results: Over 3.8 million patient records, including 13,167 second primary CNS tumors, were extracted from SEER. The relative risk of developing a second primary CNS neoplasm is elevated in all patients diagnosed with a CNS primary cancer (SIR = 9.6), but higher in those who received radiation (SIR = 13.1) or chemotherapy (SIR = 12.6). The absolute risk of developing a second primary CNS neoplasm at 25-years is highest in CNS and endocrine cancers (CI 1.0% and 0.50%, respectively). Among long-term ( &gt; 10-year) survivors of CNS primaries, the 25-year CI of a second primary CNS neoplasm was 4.4%. Cranial radiation increased the incidence of second primary tumors in pediatric patients (25-year CI 4.8% vs 1.2%, p = 0.007), but not adults (25-year CI 5.1% vs 4.9%, p = 0.85). Chemotherapy did not increase CI in either pediatric (25-year CI 7.0% vs 5.4%, p = 0.87) or adult (25-year CI 3.6% vs 5.8%, p = 0.11) populations. Meningiomas (39.3% vs 22.0%, p = 1e-6) and glioblastomas (21.1% vs 14.6%, p = 0.03) represent a greater proportion of the second primary CNS tumors in those who received cranial irradiation. Conclusions: The risk of developing a second primary CNS neoplasm is elevated in patients with a prior CNS cancer. Cranial irradiation increased the CI of second primary tumors in pediatric patients but did not affect adult patients. The association between radiation therapy and risk for subsequent cancers may be limited to the pediatric population.

Tumor subtypes associated with prostate cancer (PCa) both as first and second primary tumors: A registry-based analysis.

e17528 Background: First primary tumors (FPT) generally are associated with decreased survival and, thus, reduced risk of second primary tumors (SPT). A greater than expected incidence of SPT may indicate causal factors shared in common with a particular FPT, especially if the converse also is observed, i.e. if incidence is also greater than expected when tumor sequence is reversed. We analyzed the Surveillance, Epidemiology, and End Results (SEER) cancer registry to identify tumors with higher than expected incidence in relation to PCa, both as FPT and SPT. Methods: We searched the SEER18 cancer database covering 18 geographical regions of the U.S. from 2000 to 2016. SEER*Stat software v.8.3.6 was used to calculate standardized incidence ratios (SIR) of various SPT after defined FPT. SIR compare the incidence of a particular cancer within subsets of the registry population as a ratio to the expected incidence from a comparable matched group derived from the general population. 813,712 men with prostatic FPT (1° PCa) were included in the analysis for SIR of any SPT, while 2,554,835 men with any FPT were included in the analysis for SIR of prostatic SPT (2° PCa). Results were stratified by race and latency. Reciprocal SIR (1° PCa; 2° PCa) for values with p &lt; 0.05 are reported. Results: Aggregate analysis of all tumors demonstrated lower than expected SIR for SPT, both for any SPT after 1° PCa and for 2° PCa after any FPT (0.69; 0.53). By contrast, six tumor subtypes – small intestine (1.17; 1.19), melanoma (1.05; 1.23), bladder (1.14; 2.02), kidney (1.22; 1.36), thyroid (1.27; 1.36), and chronic myelogenous leukemia (1.10; 1.15) – had bidirectionally increased secondary SIR in relation to PCa. The reciprocal increases were detected across racial subgroups for bladder, kidney and thyroid cancers. SIR tended to be highest in the early post-FPT period (2-11 mo.) with significant increases for bladder (1.49; 6.75), kidney (2.66; 1.87), and thyroid (1.61; 1.65) cancers. These three tumor types retained bidirectional increases in relation to PCa over intermediate latencies (12-119 mo.), but not beyond 120 mo. Conclusions: Overall, FPT were associated with lower than expected incidence of SPT, most likely as a result of shortened life expectancy. However, several tumors were identified that 1). occurred with higher than expected incidence after 1° PCa and 2). were associated with higher than expected incidence of 2° PCa. Further examination of the relationship of these tumors with PCa may identify mutual intrinsic or extrinsic factors that contribute to tumor development.

Reporting two cases of second primary brain tumors and how to differentiate from metastasis preoperatively with magnetic resonance imaging

The incidence of second primary tumors in adults is increasing due to betterment in the diagnosis and management of first primary tumors. In literature so far, second primary brain tumors are not reported. Glioblastoma has a poor prognosis despite all recent advances in its molecular genetics and treatment. We report two cases of glioblastoma presenting as second primary tumor of the brain. The first patient was a 70-year-old female with seizures who was treated for carcinoma cervix 6 years back. The second patient was a 75-year-old male patient, a known case of colonic carcinoma treated a year back, and he presented with seizure. Both the patients were operated, and biopsy turned out glioblastoma. A solitary brain lesion in the known first primary patient may be a glial tumor which needs proper evaluation since its management differs from metastasis.

Time patterns of recurrence and second primary tumors in a large cohort of patients treated for oral cavity cancer.

IntroductionRoutine follow‐up after curative treatment of patients with oral squamous cell carcinoma (OSCC) is common practice considering the high risk of second primaries and recurrences (ie second events). Current guidelines advocate a follow‐up period of at least 5 years. The recommendations are not evidence‐based and benefits are unclear. This is even more so for follow‐up after a second event. To facilitate the development of an evidence‐ and personalized follow‐up program for OSCC, we investigated the course of time until the second and subsequent events and studied the risk factors related to these events.Materials and methodsWe retrospectively studied 594 OSCC patients treated with curative intent at the Head and Neck Cancer Unit of the Radboud University Medical Centre from 2000 to 2012. Risk of recurrence was calculated addressing death from intercurrent diseases as competing event.ResultsThe 1‐, 5‐ and 10‐year cumulative risks of a second event were 17% (95% CI:14%;20%), 30% (95% CI:26%;33%), and 37% (95% CI:32%;41%). Almost all locoregional recurrences occurred in the first 2 years after treatment. The incidence of second primary tumors was relatively stable over the years. The time pattern of presentation of third events was similar.DiscussionOur findings support a follow‐up time of 2 years after curative treatment for OSCC. Based on the risk of recurrence there is no indication for a different follow‐up protocol after first and second events. After 2 years, follow‐up should be tailored to the individual needs of patients for supportive care, and monitoring of late side‐effects of treatment.

Incidence of second primary neoplasms among cancer survivors in the United States, 2000 through 2015.

1586 Background: The number of cancer survivors in the United States is projected to exceed 20 million by 2024. Survivors are at risk of developing a second primary neoplasm (SPN) – a leading cause of survivor death. We described the risk of developing a SPN among survivors of common cancers (smoking-related vs non-smoking-related) in the United States. Methods: We identified patients aged ≥18 years who were diagnosed with a primary cancer from the 10 sites with highest survival rates and stratified as smoking-related (urinary bladder, kidney &amp; renal pelvis, uterine cervix, oral cavity &amp; pharynx, and colon &amp; rectum) and non-smoking related (prostate, thyroid, breast, corpus &amp; uterus, and non-Hodgkin lymphoma) from Surveillance, Epidemiology, and End Results (2000-2015). SPN was defined as the first subsequent primary cancer occurring ≥2 months after first cancer diagnosis. Excess SPN risk was quantified using standardized incidence ratios (SIRs) stratified by sex. Results: A cohort of 2,908,349 patients (50.1% female) was identified and 260,267 (9.0%) developed SPN (7.6% of females and 10.3% of males). All index cancer sites were associated with a significant increase in SPN risk for females and males (except prostate cancer). Index smoking-related cancers (SIR range 1.20 – 2.17 for females and 1.12 – 1.91 for males) had higher increased risk of SPN than non-smoking-related cancers (SIR range 1.08 – 1.39 for females and 0.55 – 1.38 for males) relative to the general population. Conclusions: Nearly 10% of cancer survivors developed an SPN, and those with smoking-related cancers had higher risk. Given the increasing number of cancer survivors and importance of SPN as a cause of cancer death, these findings can improve secondary prevention and surveillance guidelines. [Table: see text]

Risk of second primary neoplasia in patients with oropharyngeal carcinoma: Role of HPV status in the outcome.

e17544 Background: Patients with HPV-positive oropharyngeal cancer (OPC) have better prognosis and a lower risk of appearance of second primary neoplasm (SPN) than HPV-negative OPC patients. The aim of our study was to analyze the risk of developing SPN in a large group of patients with OPC according to HPV status in the primary tumor and its relationship with toxic habits. Methods: This study includes patients from a prospective data-base: 484 OPC patients were treated from 1991 to 2017 for which the HPV DNA positivity was evaluated by PCR in available tumor specimens. HPV DNA positive samples were further tested for HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. The mean follow-up of patients included in the study was 4.9 years (SD 5.1 years). We estimated the incidence of SPN in all cancer sites and in cancer sites related to tobacco and alcohol consumption according to the HPV status in the primary tumor. Results: Ninety-nine (20.5%) out of 484 OPCs included in the study were HPV-related. During the follow-up period, 127 patients with HPV-negative tumors (33.0%) and 19 patients with HPV-positive tumors (19.2%) had a SPN. Considering only the tobacco/alcohol-related SPNs, 106 of the patients with HPV-negative tumors (27.5%), and 12 patients with HPV-positive tumors (12.1%) had a tobacco/alcohol-related SPN (P &lt; 0.0001). Five-year and 10-year SPN-free survival for HPV-negative versus HPV-positive OPC patients was 61.0% versus 81.5%, and 37.6% versus 73.8%, respectively (P &lt; 0.001). When restricting the analyses to tobacco/alcohol-related SPNs, the corresponding survival rates were 66.6% versus 86.8% and 45.9% versus 83.5% for 5-year and 10-year survival rates, respectively (P &lt; 0.0001). The frequency of tobacco/alcohol-related SPNs occurrence throughout the follow-up period for patients with HPV-negative OPC was 27.5%, for patients with HPV-positive tumors with a previous history of severe tobacco and/or alcohol use was 21.4%, and for patients with HPV-positive tumors without a history of severe tobacco and/or alcohol consumption it was 8.5% (P &lt; 0.0001). Conclusions: HPV status and previous toxic habits might allow classifying patients regarding the risk of tobacco/alcohol-related SPNs. HPV-related OPC patients without previous history of severe tobacco and/or alcohol use have a significant low risk of SPN development, particularly in those locations related to tobacco use or alcohol consumption

Epidemiology of Second Primary Tumors in Women With Ovarian Cancer.

The last large study of second primary tumors (SPTs) in women with ovarian cancer was published in 1996, prior to major changes in the differential diagnosis and treatment. The present study reports on the incidence of SPTs in a contemporary cohort of patients with a diagnosis of ovarian cancer. Ovarian cancer patients with a diagnosis of an ovarian malignancy between 1992 and 2012 were identified and characterized from 13 registries of the Surveillance, Epidemiology, and End Results database. Of 41,073 women with a diagnosis of an ovarian malignancy between 1992 and 2012, 1831 (4.5%) developed a microscopically confirmed SPT. There was no significant difference in the risk of developing an SPT at all sites between women with an ovarian cancer and the general population. There was an elevated risk of site-specific SPTs of the small intestine, vagina, thyroid gland, and acute nonlymphocytic leukemia in ovarian cancer patients compared with the general Surveillance, Epidemiology, and End Results population. Conversely, the risk of lung and non-Hodgkin lymphoma was significantly decreased in women with ovarian cancer. An elevated risk of SPTs was observed in women with mucinous, endometrioid, and germ cell tumors. White women had an overall decreased risk of developing a second primary solid tumor, whereas American Indian and Asian/Pacific Islander women had an overall increased risk of an SPT at any site. The incidence of SPTs in women with ovarian cancer was not significantly different as compared with the general population. However, divergent rates of SPTs in relation to histology, latency, age, and race were observed.

Endoscopic Submucosal Dissection of Secondary Hypopharyngeal Neoplasia in Trismus Oral Cancer Patients: Case Series Report

The incidence of second primary tumor (SPT) in head and neck (H&N) cancer patients is not uncommon [1,2]. When using image-enhanced endoscopy (IEE) screening in patients at risk, especially narrow-band imaging (NBI) endoscopy and chromoendoscopy with Lugol's solution, approximately 20% of H&N cancer patients have synchronous neoplasia in H&N regions of esophagus [1,2]. Unfortunately, some of them have trismus because of oral submucosa fibrosis secondary to long-term betel quit chewing or post-irradiation therapy, and tumor-related airway compromised. These situations make the pharyngeal passages difficult to reach with conventional endoscopes. Traditionally, hypopharyngeal neoplasia in trismus patients are managed with widest field of resection, open partial pharyngectomy and usually in conjunction with partial or total laryngectomy, which are accompanied with poor quality of life (QoL). We present three trismus patients with early hypopharyngeal neoplasia treated by transoral endoscopic submucosal dissection (ESD).

Tumor characteristics and prognosis in familial breast cancer.

BackgroundApproximately 5–10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome.MethodsWe retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months.ResultsBRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28–0,93) p = 0.028).ConclusionsThe biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

Second Primary Tumours in Head and Neck Cancer

Introduction and objectivesHead and neck cancer patients have a higher risk of second primary tumours than the general population. The most frequent locations are head and neck, lung and oesophagus, decreasing long-term survival.The aim of this work was to analyse the incidence, location according to index tumour and stage, chronology, patient age, and survival after diagnosis. MethodRetrospective study on 579 patients with head and neck squamous cell carcinoma, treated with curative intent, with a minimum 24-month follow-up. Early stages (I/II) were 42.4%, and 57.6% were stages III and IV. ResultsSecond primary tumour incidence was 15% (87/579), with 9.2% (8/97) developing a third tumour. The most frequent locations of the second tumours were head and neck, 37.9% (33/87); lung, 36.8% (32/87); oesophagus, 5.7% (5/87); and colon, 5.7% (5/87). Five- and 10-year survival in patients without a second tumour was 65.1% and 52.7%, respectively, versus 58.7% and 40.2% in those who developed one. ConclusionsThe incidence of second primary tumours increased in the last decade, having a negative effect on survival. Since no specific early diagnosis tool is available, alcohol and tobacco avoidance along with scheduled follow-up are suggested procedures to reduce its incidence.

Segundos tumores primarios en cáncer de cabeza y cuello

Introduction and objectivesHead and neck cancer patients have a higher risk of second primary tumours than the general population. The most frequent locations are head and neck, lung and oesophagus, decreasing long-term survival.The aim of this work was to analyse the incidence, location according to index tumour and stage, chronology, patient age, and survival after diagnosis. MethodRetrospective study on 579 patients with head and neck squamous cell carcinoma, treated with curative intent, with a minimum 24-month follow-up. Early stages (I/II) were 42.4%, and 57.6% were stages III and IV. ResultsSecond primary tumour incidence was 15% (87/579), with 9.2% (8/97) developing a third tumour. The most frequent locations of the second tumours were head and neck, 37.9% (33/87); lung, 36.8% (32/87); oesophagus, 5.7% (5/87); and colon, 5.7% (5/87). Five- and 10-year survival in patients without a second tumour was 65.1% and 52.7% respectively, versus 58.7% and 40.2% in those who developed one. ConclusionsThe incidence of second primary tumours increased in the last decade, having a negative effect on survival. Since no specific early diagnosis tool is available, alcohol and tobacco avoidance along with scheduled follow-up are suggested procedures to reduce its incidence.