Second Primary Cancers In Patients Research Articles

Second primary cancers among females with a first primary breast cancer: a population-based study in Northern Portugal.

To estimate the incidence rate of second primary cancers (SPCs) and the cumulative incidence of metachronous [diagnosed > 2 months after a first primary cancer(FPC)] SPCs in patients with a breast FPC, and to compare the incidence of SPC [overall, synchronous (≤ 2 months of the FPC) and metachronous] with that expected in the general female population. A cohort of patients with a breast FPC from the North Region Cancer Registry of Portugal, diagnosed in 2000-2010 (n = 15,981), was followed to 31 December 2015 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs considering death as a competing event, and incidence rates and standardized incidence ratios of SPCs were estimated. The diagnosis of an SPC occurred in 1229 (7.7%) of patients with a breast FPC. SPCs occurred mainly in the breast, followed by digestive organs, lung, thyroid, and female genital organs. Globally, patients with a breast FPC had a higher incidence for all types of cancer compared to the general female population, and in particular for cancers of the breast, stomach, colon, lung, lymphoma, uterus, and ovary. The 10-year cumulative incidence of metachronous SPCs following a breast FPC was 6.6% and the corresponding 10-year cumulative mortality was 26.2%. In Portugal, patients with a breast FPC have a higher incidence of cancer compared to the general female population, highlighting important aspects of care, surveillance, and counselling among this growing number of patients.

Impact of thyroid hormone replacement on the risk of second cancer after thyroidectomy: a Korean National Cohort Study

We aimed to investigate the effect of thyroid hormone administration on the risk of second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer. Data were extracted from the medical billing data of the Health Insurance Review and Assessment Service in South Korea. Patients between 19 and 80 years old who underwent thyroid surgery at least once between January 2009 and June 2020 were included. Data of patients with second primary cancer and control patients with matched age, sex, operation date, and follow-up duration were extracted at a ratio of 1:4. A nested case–control analysis was performed to exclude length bias to confirm the correlation between the duration of thyroid hormone administration, dose, and incidence of second primary cancer. Of the 261,598 patients who underwent surgery for thyroid cancer included in the study, 11,790 with second primary cancer and 47,160 without second primary cancer were matched. The average dose of thyroid hormone increased the adjusted odds ratio (OR) for both low (≤ 50 μg, OR 1.29, confidence interval (CI) 1.12–1.48) and high (< 100 μg, OR 1.24, CI 1.12–1.37) doses. Analyzing over time, the adjusted OR of second primary cancer increased, especially in short (≤ 1 year) (OR 1.19; CI 1.06–1.34) and long (> 5 years) duration (OR 1.25; CI 1.10–1.41). In conclusion, insufficient and excessive thyroid hormone replacement might be linked to increased second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer.

Risk of second primary cancers in patients with rectal neuroendocrine neoplasms: a surveillance, epidemiology, and end results analysis.

While an elevated risk of second primary cancers (SPCs) has been observed in many other cancers, risk of SPCs has not been quantified in patients with rectal neuroendocrine neoplasms (NENs). Survivors of primary rectal NENs diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER)-18 registries. Relative risk of SPCs was estimated as the standardized incidence ratio (SIR), which was calculated using SEER*Stat software. Between 2000 and 2018, a total of 15836 patients diagnosed with rectal NENs, of whom 1436 (9.1%) received diagnosis of SPCs (SIR: 1.19, 95%CI: 1.13-1.26). The majority of patients were aged 50-69 and had their first cancer diagnosed at the localized stage. Male survivors had a higher propensity for developing SPCs overall, while female survivors exhibited higher risks of specific SPCs. Age at diagnosis of rectal NENs influenced the risk of SPCs, with younger patients having greater risks. A statistically significant increase in the incidence of SPCs was observed among patients aged 30-64 years. Black patients had higher relative risks of certain SPCs, while White patients had a lower risk of subsequent melanoma. Trend analysis revealed that the highest excess burden of SPCs was observed in the years 2000 to 2002. Risk of SPCs remained elevated within the first four years post-diagnosis for survivors of rectal NENs, but diminished thereafter. The study revealed that individuals who survived rectal NENs were at an elevated risk of developing SPCs compared to the general population. Our results hold important implications for the formulation of lifelong surveillance recommendations for cancer survivors.

Second Primary Cancer Among Patients With Papillary Thyroid Carcinoma Following the Chernobyl Disaster

To our knowledge, there are no complete population-based studies of the risks of developing second malignant tumors after papillary thyroid carcinoma (PTC) in patients following the Chernobyl nuclear accident. To study the risk of second primary cancers in patients with PTC after the Chernobyl disaster. This was a retrospective cohort study conducted in the Republic of Belarus over a 31-year time frame evaluating patients with primary PTC and second malignant tumors. Personal data from the Belarussian Cancer Registry were used in the investigation, and only second primary cancers were included in the analysis. Patients were observed from January 1, 1990, to December 31, 2021, for the establishment of second primary malignant tumors. For analysis, synchronous and metachronous tumors were grouped into 1 group (second primary cancer group). If the patient had more than 2 cancers, they were observed until development of a second tumor and, subsequently, the development of a third tumor. The starting point for calculating the number of person-years was the date of thyroid cancer diagnosis. The end point for calculating the number of person-years was the date of diagnosis of the second primary malignant tumor, the date of death, the date of the last visit of the patient, or December 31, 2021 (the end the of study period). The incidence of a second primary malignant tumor with PTC was calculated for the study groups using standardized incidence ratios. Of the 30 568 patients with a primary PTC included in this study, 2820 (9.2%) developed a second malignant tumor (2204 women and 616 men); the mean (SD) age of all patients at time of the primary cancer was 53.9 (12.6) years and at time of the secondary cancer was 61.5 (11.8) years. Overall, the standardized incidence ratio was statistically significant for all types of cancer (1.25; 95% CI, 1.21-1.30), including solid malignant tumors (1.20; 95% CI, 1.15-1.25) and all leukemias (1.61; 95% CI, 2.17-2.13). Cancers of the digestive system (466 cases [21.1%]), genital organs (376 cases [17.1%]), and breasts (603 cases [27.4%]) were the most prevalent second primary tumors in women following PTC. Second primary tumors of the gastrointestinal tract (146 cases [27.7%]), genitourinary system (139 cases [22.6%]), and urinary tract (139 cases [22.6%]) were the most prevalent in men. Urinary tract cancers (307 cases [10.9%]) and gastrointestinal tumors (612 cases [21.4%]) were the most prevalent second primary tumors overall. This cohort study reports the increased incidence of solid secondary tumors in men and women over a 31-year time frame after the Chernobyl disaster. Moreover, there was a statistically significant increased risk of second tumors of the breast, colon, rectum, mesothelium, eye, adnexa, meninges, and adrenal glands as well as Kaposi sarcoma. These data might have an effect on the follow-up of this cohort of patients to detect secondary malignant tumors at an early stage.

Risk of second primary cancer in patients with head and neck squamous cell carcinoma: a systemic review and meta-analysis.

Second primary cancer is a common event in patients with head and neck squamous cell carcinoma. However, the incidence and relevant factors vary by studies. We conducted a systematic review and meta-analysis of observational studies to estimate the incidence and relevant risk factors. PubMed and Web of Science were searched for studies published between January 2000 and December 2020 that reported the incidence of SPC in HNSCC patients. Per 1000-person-year incidence and odds ratios were used to estimate the incidence and potential risk factors. Due to the high heterogeneity, random-effects models were used to estimate the incidence and 95% confidence interval. Seven thousand seven hundred thirteen articles were identified from the databases, in which 60 studies were included in this meta-analysis. The pooled incidence of the total, synchronous, and metachronous SPC in patients with HNSCC were 29.116 per 1000-person-year, 6.960 per 1000-person-year, and 26.025 per 1000-person-year, respectively. The head and neck region was the most common area where SPC occurred, followed by the lung (7.472 per 1000-person-year) and upper digestive tract (2.696 per 1000-person-year). Smoking, alcohol consumption, betel quid chewing, primary cancer of T1-2, and N0 were risk factors, while HPV infection (OR 0.47, 95% CI 0.30-0.72) was the protective factor. SPC is frequently observed in HNSCC patients and had great impact on the prognosis. The findings could promote a more individualized follow-up strategy for SPC in HNSCC patients. This systemic review and meta-analysis provide sufficient evidence for the establishment of the follow-up strategy for head and neck squamous cancer patients.

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors

BackgroundLung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. Patients and methodsThis retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. ResultsAmong the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min–max: 7–173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27–0.58). ConclusionTreatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Pretreatment elevated mean corpuscular volume as an indicator for high risk esophageal second primary cancer in patients with head and neck cancer

ObjectiveEsophageal cancer is the most common second primary cancer (SPC) in patients with head and neck cancer (HNC). Esophageal SPC has a negative impact on survival. Elevated mean corpuscular volume (MCV) is an accepted predictor of esophageal cancer risk. The aim of this study was to elucidate the usefulness of elevated MCV as an indicator of a high risk for esophageal SPC. MethodsWe retrospectively reviewed the medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinoma who underwent chemoradiotherapy between 2003 and 2012. We excluded patients younger than 20 years or who had received treatment for esophageal cancer and who had a histologically unproven lesion. Patients were divided into two groups according to their MCV. The cut-off for MCV was defined by receiver operating characteristics curve analysis. The primary endpoint was the cumulative incidence of esophageal SPC. ResultsA total of 295 patients were included. The median follow-up period for surviving patients was 7.4 years and the optimal cut-off point was 99.0 fL. One hundred ninety-five patients (66%) had an MCV < 99.0 fL and 100 (34%) had an MCV ≥ 99.0 fL. The 5-year cumulative incidence in patients with an MCV < 99.0 fL and ≥ 99.0 fL was 8.7% and 27%, respectively. In the multivariate analysis, an MCV ≥ 99.0 fL (HR=2.2; 95%CI, 1.1-4.2) was an independent risk factor. ConclusionMCV ≥ 99.0 fL was found to be a risk factor for esophageal SPC. We, therefore, recommend that patients with an MCV ≥ 99.0 fL should undergo intensive monitoring.

Relationship between metastasis and second primary cancers in women with breast cancer

BackgroundBreast cancer (BC) survivors have an increased risk of developing second primary cancers (SPCs); however, it is still unclear if metastasis is a risk factor for developing SPCs. Usually, long-term cancer survivors face an increased risk of developing SPCs; however, less attention has been paid to SPCs in patients with metastatic cancer as the survival outcomes of the patients are greatly reduced.MethodsA total of 17,077 American women diagnosed with breast cancer between 2010 and 2018 were identified from Surveillance, Epidemiology, and End Results (SEER) database and were included in the study. The clinical characteristics, standardized incidence ratio (SIR), standardized mortality ratio (SMR), and patterns of SPCs in BC patients with no metastasis, regional lymph node metastasis, and distant metastasis were investigated. Kaplan-Meier method was used to compare the prognosis of BC patients after developing SPCs with different metastatic status. XGBoost, a high-precision machine learning algorithm, was used to create a prediction model to estimate the prognosis of metastatic breast cancer (MBC) patients with SPCs.ResultsThe results reveal that the SIR (1.01; 95% CI, 0.99–1.03, p>0.05) of SPCs in non-metastasis breast cancer (NMBC) patients was similar to the general population. Further, patients with regional lymph node metastasis showed an 8% increased risk of SPCs (SIR=1.08, 95%CI, 1.05–1.11, p<0.05), and patients with distant metastasis had a 26% increased risk of SPCs (SIR=1.26, 95%CI, 1.16–1.37, p<0.05). The SIR of SPCs in all patients below the age of 40 was the highest, which decreased with age. Patients with poorly differentiated cancers, large tumor size, and late N stage had an increased risk of SPCs. However, an increase in SIR of SPCs was observed in distant MBC patients, even at the early T1 (SIR=1.60, 95% CI, 1.22–1.98, p<0.05) and N1 (SIR=1.27, 95% CI, 1.10–1.44, p<0.05) stage. An increase in the SIR of SPCs was observed in patients with triple-negative BC, and the SIR of SPC increased with metastasis development in BC patients with luminal A subtype. The peak of SPCs risk occurrence was earlier in MBC patients (4-6 months and 10 months) compared to NMBC patients (12 months). The effect of metastasis on the prognosis of SPCs patients was dependent on the type of SPCs. Meanwhile, the XGBoost model was created to predict the 3-year (AUC=0.873) and 5-year survival (AUC=0.918) of SPCs in MBC patients.ConclusionsOur study provides novel insight into the impact of metastasis on SPCs in BC patients. Metastasis could promote the second primary tumorigenesis which further increased cancer-related deaths. Therefore, more attention should be paid to the occurrence of SPCs in MBC patients.

Treating with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Accompanying Lower Incidence of Second Primary Cancers.

Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan’s National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged <65 years accounted for 53.15%. Patients aged ≥65 years accounted for 40.18% and 53.24% in the SPLC and SPEC groups, respectively. Females accounted for 50.3% of patients without SPC, 54% of the SPLC group, and 44.3% of the SPEC group. Univariate and multivariate Cox proportional hazard models showed increased hazard ratios for smoking, hypertension, and diabetes mellitus, and lower HRs for surgery, chemotherapy, radiotherapy, and TKIs. Patients undergoing surgery, chemotherapy, and radiotherapy were associated with a lower risk of SPCs. Treatment with EGFR TKIs was a significant and independent factor associated with lower incidence of SPCs. This study may encourage researchers to establish predictive models based on our results to assess the risk factors for SPCs, and therefore, early screening and intervention could be applied, and the SPCs-related mortality and relevant medical costs could be reduced.

Detection of distant metastases and distant second primary cancers in head and neck squamous cell carcinoma: comparison of [18F]FDG PET/MRI and [18F]FDG PET/CT

PurposeThis prospective study aimed to compare the diagnostic performance of [18]FDG PET/MRI and PET/CT for the detection of distant metastases and distant second primary cancers in patients with head and neck squamous cell carcinoma (HNSCC).MethodsA total of 103 [18F]FDG PET/MRI examinations immediately followed by PET/CT were obtained in 82 consecutive patients for staging of primary HNSCC (n = 38), suspected loco-regional recurrence/follow-up (n = 41) or unknown primary HNSCC (n = 3). Histology and follow-up > 2 years formed the standard of reference. Blinded readers evaluated the anonymized PET/MRI and PET/CT examinations separately using a 5-point Likert score. Statistical analysis included: receiver operating characteristic (ROC) analysis, jackknife alternative free-response ROC (JAFROC) and region-of-interest (ROI)-based ROC to account for data clustering and sensitivity/specificity/accuracy comparisons for a score ≥ 3.ResultsDistant metastases and distant second primary cancers were present in 23/103 (22%) examinations in 16/82 (19.5%) patients, and they were more common in the post-treatment group (11/41, 27%) than in the primary HNSCC group (3/38, 8%), p = 0.039. The area under the curve (AUC) per patient/examination/lesion was 0.947 [0.927–1]/0.965 [0.917–1]/0.957 [0.928–0.987] for PET/MRI and 0.975 [0.950–1]/0.968 [0.920–1]/0.944 [0.910–0.979] for PET/CT, respectively (p > 0.05). The diagnostic performance of PET/MRI and PET/CT was similar according to JAFROC (p = 0.919) and ROI-based ROC analysis (p = 0.574). Sensitivity/specificity/accuracy for PET/MRI and PET/CT for a score ≥ 3 was 94%/88%/89% and 94%/91%/91% per patient, 96%/90%/91% and 96%/93%/93% per examination and 95%/85%/90% and 90%/86%/88% per lesion, respectively, p > 0.05.ConclusionsIn HNSCC patients, PET/MRI and PET/CT had a high and similar diagnostic performance for detecting distant metastases and distant second primary cancers.

Genetic Risk of Second Primary Cancer in Breast Cancer Survivors: The Multiethnic Cohort Study.

This multiethnic study links germline pathogenic variants in BRCA1, BRCA2, and ERCC2 to the development of second primary cancer in breast cancer survivors, providing biological insights and biomarkers to guide patient monitoring.

Late genitourinary and gastrointestinal toxicity and radiation-induced second primary cancers in patients treated with low-dose-rate brachytherapy

To evaluate late genitourinary (GU) and gastrointestinal (GI) toxicities and radiation-induced second primary cancers (RISPCs) in patients who received low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy for prostate cancer. This retrospective study included 897 consecutive patients who received LDR-BT between July 2004 and July 2015 in our institution. Adverse events and the incidence of second primary cancers were evaluated at 1, 3, 6, 12, 18, 24, 30, 36, 48, 54, and 60 mo after LDR-BT and then once a year. Related factors to ≥grade 2 (G2) toxicity were evaluated using the Cox proportional-hazards model. The median follow-up time was 85.2 (interquartile range: 66.8-111.3) mo. The cumulative incidence rates of ≥G2 GU toxicity at 5 and 10 yrs after LDR-BT were 11.2% and 14.7%, respectively. The International Prostate Symptom Score before LDR-BT (continuous) (hazard ratio [HR]: 1.03), no neoadjuvant androgen deprivation therapy (HR: 1.69), and combination external beam radiotherapy (HR: 3.30) were risk factors related to the incidence of ≥G2 GU toxicity. The cumulative incidence rates of ≥G2 GI toxicity at 5 and 10 yrs after LDR-BT were 3.3% and 3.3%, respectively. Age (continuous) (HR: 1.09), body mass index (continuous) (HR: 0.87), and rectum V100 (continuous) (HR: 1.64) were risk factors related to ≥G2 GI toxicity. A total of 12 (1.3%) patients developed metachronous RISPCs (bladder cancer: 9; rectal cancer: 3). The incidence rates of late GU and GI toxicities and RISPCs after LDR-BT were low.

Predicting the Risk Factors of Second Primary Cancer in Patients with Hepatocellular Carcinoma.

Screening for cancer and improved treatments have not only improved treatment outcomes and patient survival but have also led to an increase in the number of second primary cancers (SPCs). Hepatocellular carcinoma has been a common occurrence in Taiwan over the past decade. The mortality rate is second only to malignant tumors of lung cancer, and it also represents the fourth highest cancer medical expenditure. This study aimed to use machine learning to identify the risk factors for Hepatocellular carcinoma survivors. Of 378,445 datasets, including 15,251 from patients with SPCs, were collected; 18 predictive variables were considered risk factors for SPCs based on the physician panel discussion. The machine learning techniques employed included support vector machine, C5 decision tree, and random forest. SMOTE (Synthetic Minority Oversampling Technique) sampling method was used to resolve the imbalance problem. The results showed that the top 5 risk factors for SPCs were tumor size, clinical stage, surgery, total bilirubin, and BCLC Stage. The support vector machine method had the highest predicted accuracy (0.7673). The risk factors extracted from the classification models and association rules will be used to provide valuable information for HCC therapy.

Incidence and Predictors of Second Primary Cancers in Patients With Neuroendocrine Tumors

This retrospective cohort study examines the risk factors and predictors of second primary cancers after being diagnosed with neuroendocrine tumors.

Assessment of Trends in Second Primary Cancers in Patients With Metastatic Melanoma From 2005 to 2016

To date, the risk of developing second primary cancers (SPCs) after the first primary melanoma has not been studied in the era of immune checkpoint inhibitors (ICIs). To assess differences in the risk of SPCs in patients with primary melanoma before (2005-2010) and after (2011-2016) the introduction and approval of ICIs. Population-based cohort study using the Surveillance, Epidemiology, and End Results database from January 2005 to December 2016 of patients diagnosed with metastatic melanoma. Data were analyzed from January 4 to June 30, 2020. Receipt of immunotherapy or other anticancer agents. The primary outcome was the development of second primary cancers in patients with melanoma. Standardized incidence ratios (SIRs) were calculated for the development of SPCs before and after the introduction of ICIs. Among 5016 patients with diagnosed metastatic melanoma, 2888 (58%) were younger than 65 years at the time of diagnosis, and 3441 (69%) were male. From 2005 to 2010, SIRs were 3.24 (95% CI, 0.08-18.04) for small intestine cancer, 1.93 (95% CI, 1.14-3.05) for lung and bronchus cancer, 2.77 (95% CI, 1.02-6.03) for kidney cancer, and 7.29 (95% CI, 2.93-15.02) for myeloma. From 2011 to 2016, SIRs were 9.23 (95% CI, 1.12-33.35) for small intestine cancer, 1.54 (95% CI, 0.71-2.93) for lung and bronchus cancer, 2.66 (95% CI, 0.73-6.82) for kidney cancer, and 5.90 (95% CI, 1.61-15.10) for myeloma. The overall risk of developing SPCs in individuals who survived the first primary melanoma was 65% higher (SIR, 1.65; 95% CI, 1.35-2.00) in the pre-ICIs period and 98% higher (SIR, 1.98; 95% CI, 1.57-2.45) in the post-ICIs period than the overall cancer incidence rate in the general population. In this study, an increase in the overall risk of second primary cancers after melanoma after the introduction of immune checkpoint inhibitors was observed. The pattern of SPCs has been altered in the era of systemic therapy. Close monitoring and screening for SPCs may be warranted in patients with metastatic melanoma.

Risk of second primary malignancies among patients with carcinoid of the lung

ObjectivesLittle is known about the etiology of pulmonary carcinoids (PC). Associations with other types of cancer may identify shared risk factors but results from earlier studies were inconclusive. The aim of the present study was to explore the association between PC and other primary malignancies for identifying risk factors. MethodsA query of the nationwide Netherlands Cancer Registry generated data about patients diagnosed with PC from 1989 to 2018. The occurrence of second primary malignancies was evaluated separately for year 1 and years 2−30. The expected numbers of second primary malignancies were calculated using incidence reference tables, controlling for age, gender and period. Confidence intervals (95 % CI) for the ratio between observed and expected numbers (SIR: standardized incidence ratio) were calculated using Poisson distributions. ResultsIn a total of 2933 patients with PC, 425 consecutive primary malignancies were observed in 376 patients. Concomitant diagnoses in the first year mainly comprised lung (n = 59) and renal cancer (n = 14). Metachronous malignancies beyond the first year were most common for breast (n = 50), colorectal (n = 41), prostate (n = 32), and lung cancer (n = 29). Beyond year 1, the overall risk of second primary cancer in patients with PC was similar to the risk within the general population (n = 256, SIR = 1.12, 95 % CI 0.99–1.27). Increased risks were observed for soft tissue sarcoma (n = 5, SIR = 3.52, 95 % CI 1.14–8.22) and GEPNET (n = 4, SIR = 4.30, 95 % CI 1.17–11.01). ConclusionsConcomitant diagnosis of PC with other cancers is common, reflecting surveillance diagnostics. Apart from MEN-1 family history, no shared risk factors could be identified.

Second primary cancers and recurrence in patients after resection of colorectal cancer: An integrated analysis of trials by Japan Clinical Oncology Group: JCOG1702A.

Improvements in early detection and treatment have resulted in an increasing number of long-term survivors of colorectal cancer (CRC). For the survivors, second primary cancer and recurrence are important issues; however, evidence for an appropriate surveillance strategy remains limited.This study aimed to investigate the frequency and timing of second primary cancer in patients after surgery for exploring an appropriate surveillance strategy by using an integrated analysis of three large-scale randomized controlled trials in Japan. The eligibility criteria of three trials included histologically confirmed CRC and having received surgery. The timing, site and frequency of second primary cancers and recurrence were investigated. Risk factors associated with second primary cancers were also examined. The standardized incidence ratio (SIR) of second primary cancers compared with the national database of the Japan Cancer Registry was estimated. A total of 2824 patients were included in this study. The cumulative incidence of second primary cancer increased over time. The SIR of any second primary cancer was 1.07 (95% CI: 0.94-1.21). The SIR for second primary cancers of colon was 1.09 (95% CI: 0.79-1.47). The cumulative incidence of recurrence almost reached plateau at 3years. A common surveillance strategy for the general population can be applied even for curatively resected CRC patients, as the risk of second primary cancers was almost the same as that of the general population.

Incidence and Mortality of Second Primary Cancers in Danish Patients With Retinoblastoma, 1943-2013

In heritable retinoblastoma, there is a significantly increased risk of second primary cancers (SPCs). Improved knowledge about the incidence and influence of heritability and treatment is important during therapy for patients with retinoblastoma. To assess the incidence of SPC in patients diagnosed with retinoblastoma in Denmark from 1943 to 2013 with a focus on heritability and the association of external radiotherapy with mortality. In this retrospective cohort study, data were extracted from the Danish Ocular Oncology Group Database containing complete data on all patients diagnosed with retinoblastoma , and obtained from the Danish Cancer Registry, which includes information on all patients with cancer from 1943 to December 31, 2013. Data analysis was conducted from December 1, 2017, to October 1, 2019. Data on 323 patients were included. Heritability and retinoblastoma treatment. Standardized incidence rate, excess absolute risk, cumulative incidence of SPC, and mortality from SPC. Association of heritability and treatment with outcomes was estimated. Of the 323 patients included in the analysis, 181 were men (56%), 133 had heritable retinoblastoma (41%), and 190 had nonheritable retinoblastoma (59%). The median age at diagnosis of SPC was 32.4 (interquartile range, 15.4-43.9) years in patients with heritable retinoblastoma and 38.6 (interquartile range, 20.5-49.4) years in those with nonheritable retinoblastoma. Twenty-five SPCs were identified in patients with heritable retinoblastoma vs 14 in patients with nonheritable retinoblastoma. Standardized incidence rate (SIR) of SPC in patients with heritable retinoblastoma was 11.39 (95% CI, 7.37-16.81) with an excess absolute risk of 70 cases per 10 000 person-years; the highest SIRs were for sarcoma (181.13; 95% CI, 98.94-303.92) and malignant melanoma (26.78; 95% CI, 9.78-58.30). The SIR for SPC in patients with nonheritable retinoblastoma was 1.52 (95% CI, 0.81-2.60). The cumulative incidence of SPCs at age 60 years was significantly higher in patients with heritable retinoblastoma (51%) compared with those with nonheritable retinoblastoma (13%) (P < .001) (hazard ratio, 5.0; 95% CI, 2.5-10.3). No significant differences were identified in overall risk of SPC in patients with heritable retinoblastoma treated with 3 different modalities: external radiotherapy, plaque (but no external) radiotherapy, and enucleation only, but an increased proportion of sarcomas was noted in the irradiated field. Mortality due to SPC was also higher in survivors of heritable retinoblastoma compared with those with nonheritable retinoblastoma (cumulative mortality, 34% vs 12% at age 60 years; P = .03). The findings of this study suggest that the incidence and mortality associated with SPC were significantly higher in patients with heritable retinoblastoma vs patients with nonheritable retinoblastoma. The largest increases in risk were noted for sarcoma and malignant melanoma. External radiotherapy did not appear to increase the risk. These findings are relevant when treating patients with retinoblastoma to manage the risk for SPC.

Pretreatment age and serum lactate dehydrogenase as predictors of synchronous second primary cancer in patients with nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common cancer and is treated primarily by chemotherapy and radiotherapy. However, NPC with synchronous second primary cancer (SSPC) is very rare and its risk factors, treatment and prognosis remain unclear. In this study, we aimed to analyze patients with NPC and SSPC, and attempt to find potential predictors for these patients. We retrospectively collected 681 patients with NPC from 2006 to 2018. Patients in this study were divided into two groups: those patients with SSPC and those without SSPC. We then analyzed the demographic data and survival of these two groups. Independent predictors of SSPC were determined by multivariate regression analysis. A comprehensive review of the literature was also performed. We identified 17 NPC patients with SSPC in our case series and 13 cases in the literatures, and the most common SSPC is lung (16.1%). In univariate analysis, NPC patients with SSPC had older age (P<0.001) and higher serum lactate dehydrogenase (LDH) (P=0.008), compared with those without SSPC. In multivariate analysis, old age (P=0.001) and high serum LDH (P=0.023) remained independent predictors of SSPC, and a predictive equation model was established. NPC patients with SSPC had a significantly lower 5-year disease-specific survival rate compared with patients without SSPC (34.0% vs. 77.6%, P<0.001) CONCLUSION: This study demonstrated that pretreatment age and serum LDH were independent predictors for SSPC in NPC patients. These independent factors can be used for early detection, and better facilitate the design of more appropriate treatment by medical professionals.

Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer.

Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. With 13945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69-50·32] compared with risk without family history (RR 19·12, 95% CI 17·88-21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35-1·61 vs. RRno FH = 1·40, 95% CI 1·32-1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for insitu SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83-4·72) vs. those without SPC (1·04). Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3-4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and insitu squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established. Linked Comment:Youlden and Baade. Br J Dermatol 2020; 183:414-415.