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ABSTRACT Objective Methods Results Conclusions We aimed to investigate the pattern, risk, and treatment of subsequent events after curative‐intent treatment of lip cancer.This retrospective cohort study included 313 patients treated for lip cancer from 2011 to 2021 in a tertiary oncological center.After a median follow‐up time of 29.16 months, 145 (46.32%) patients presented with second primary tumors, 93% of which were skin carcinomas. Locoregional recurrence occurred in 7.9% of cases, with 2.5% with nodal recurrence. The 1‐, 5‐, and 10‐year cumulative second primary tumor probabilities were 32.8%, 60.92%, and 70.92%, respectively. A higher risk was observed in elderly patients and basal cell carcinoma cases located on the cutaneous surface of the upper lip. Regional metastasis but not second primary tumors negatively impacted survival.Our study helps fill a literature gap, structuring specific recommendations regarding evaluations and follow‐up protocols for patients with lip cancer. Since cutaneous second primary tumors were the most common second event, standard skin examination is key. Age and histology were significant predictors for second primary tumors. For cases of locally advanced lip squamous cell carcinoma, standard guidelines for head and neck cancer must be followed. [ABSTRACT FROM AUTHOR]

Background: Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies. Methods: This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model. Results: Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39–1.48], P = 0.518). History of radiotherapy emerged as a significant risk factor (sub-distribution hazard ratio [SHR] = 21.61 [2.81–166.14], P = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e−8 [9.81 e−9–1.08 e−7], P ＜ 0.001). Conclusions: These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms.

Aim: To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). Methods: We identified all patients diagnosed with incident RCC during 1995–2019, using population‐based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. Results: The absolute 1‐ and 20‐year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person‐years (PY) (SIR, 2.3; 95% CI: 2.1–2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow‐up (SIR, 1.3; 95% CI: 1.2–1.4), and 6 per 1000 PY beyond 5 years of follow‐up (SIR, 1.4; 95% CI: 1.3–1.5). The sustained elevated cancer risk beyond 1 year of follow‐up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006–2019 than in 1995–2005, but only during the first year of follow‐up. Conclusion: Patients with incident RCC have a sustained 40% elevated long‐term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract Objectives We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. Methods We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. Results A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p

Objectives: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. Methods: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. Results: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). Conclusions: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial. [ABSTRACT FROM AUTHOR]

Background: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk‐prediction model (called SPLC‐RAT) was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking. The predictive performance of SPLC‐RAT was evaluated in a hospital‐based cohort of lung cancer survivors. Methods: The authors analyzed data from 8448 ever‐smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997–2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC‐RAT and further explored the potential of improving SPLC detection through risk model‐based surveillance using SPLC‐RAT versus existing clinical surveillance guidelines. Results: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person‐years. The application of SPLC‐RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10‐year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC‐RAT development cohort), the observed SPLC incidence was significantly elevated in the high‐risk versus low‐risk subgroup (13.1% vs. 1.1%, p < 1 × 10–6). The risk‐based surveillance through SPLC‐RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow‐ups needed to detect one SPLC (162 vs. 202). Conclusion: In a large, hospital‐based cohort, the authors validated the predictive performance of SPLC‐RAT in identifying high‐risk survivors of SPLC and showed its potential to improve SPLC detection through risk‐based surveillance. Plain Language Summary: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC).However, no evidence‐based guidelines for SPLC surveillance are available for lung cancer survivors.Recently, an SPLC risk‐prediction model was developed and validated using data from population‐based epidemiological cohorts and clinical trials, but real‐world validation has been lacking.Using a large, real‐world cohort of lung cancer survivors, we showed the high predictive accuracy and risk‐stratification ability of the SPLC risk‐prediction model.Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model‐based surveillance strategies compared to the existing consensus‐based clinical guidelines, including the National Comprehensive Cancer Network. Given the rapidly growing number of lung cancer survivors who are now at high risk of developing second primary lung cancer (SPLC), previous studies have identified SPLC risk factors and developed SPLC risk‐prediction models, but they lack insight into real‐world validation to help improve clinical decision‐making in SPLC surveillance for lung cancer survivors. Using a large, hospital‐based real‐world cohort of lung cancer survivors, the authors validated the predictive accuracy of an SPLC risk‐prediction model (area under the curve of 0.81), that can identify high‐risk lung cancer survivors for SPLC and can be incorporated into clinical decision‐making for SPLC surveillance to improve the systematic management of lung cancer survivors. [ABSTRACT FROM AUTHOR]

Abstract Aim To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). Methods We identified all patients diagnosed with incident RCC during 1995–2019, using population‐based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. Results The absolute 1‐ and 20‐year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person‐years (PY) (SIR, 2.3; 95% CI: 2.1–2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to

This study was performed to analyse the age-specific characteristics of head and neck second primary malignancies (SPMs) in patients treated for nasopharyngeal carcinoma (NPC). The medical records of 56 NPC patients diagnosed with head and neck SPMs were reviewed retrospectively. Patients < 45 years old at NPC diagnosis were assigned to the younger group and those ≥ 45 years of age were assigned to the older group. The treatment of the index NPC, latency period, pathological TNM stage, survival status, and SPM subsite were analysed. Patients in the older group were found to have a shorter median latency period than those in the younger group: 8.5 years (range 3–20 years) versus 11 years (range 1–30 years) (P = 0.015). The proportion of SPMs in the jaw was significantly higher in the younger group (P = 0.002). Patients in the younger group receiving radiotherapy with chemotherapy had a shorter latency period (P = 0.003) and higher risk of developing SPMs in the jaw (P = 0.036) than those receiving radiotherapy alone. A long-term and age-dependent regular customised follow-up strategy for NPC is necessary for the prevention and early detection of head and neck second primary malignancies. [ABSTRACT FROM AUTHOR]

Background/Aims Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than Helicobacter pylori infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer. Methods We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and H. pylori infection were quantitatively analyzed. Results We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35–2.98, I2 = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63–13.80, I2 = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, H. pylori eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88–1.59, I2 = 10%). Conclusions Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).

Background: Despite obtaining a good prognosis and long life expectancy, survivors of thyroid cancer can nevertheless develop subsequent primary cancer (SPC). We investigated the risk and types of SPC in patients with thyroid cancer and compared them with subjects without thyroid cancer history (controls). Methods: We conducted a nationwide, population-based, retrospective cohort study based on the Korean National Health Insurance Database. A total of 432,654 patients diagnosed with thyroid cancer between 2004 and 2019 were 1:1 matched with controls for age, sex, income, and region of residence. The hazard ratios (HR) and 95% confidence intervals (CI) of SPC were estimated using Cox proportional hazard models. Results: In total, 78,584 (18.2%) patients with thyroid cancer and 49,979 (11.6%) controls were diagnosed with SPCs over a mean follow-up of 6.9 years. Patients with thyroid cancer had a higher risk of SPC at any site (adjusted HR, 1.62; 95% CI, 1.60–1.64) than the controls. The risk of SPCs was particularly high for patients diagnosed with thyroid cancer at a younger age (<40 years) and within 5 years. Conclusions: Medical caregivers should consider the long-term follow-up of patients with thyroid cancer and discuss the risk of SPC, especially if they complain of cancer-related symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Increased risk of second primary cancers is an unwanted consequence of cancer survivorship. While the epidemiology of second cancers is well-documented for children and older people, less is known about second cancers among adolescent and young adult (AYA) cancer survivors. Methods: Unit record data were obtained from the Queensland Cancer Register. The study cohort comprised Queensland residents aged 15 to 39 years who were diagnosed with a first primary invasive cancer between 1982 and 2013. Follow-up on second cancers was available for a minimum of 5 years to the end of 2018. Standardized incidence ratios (SIRs) were used to approximate the risk of a second primary cancer relative to the general population. Results: In total, 3086 second primary cancers were observed among 34,431 eligible AYA patients (9%), equating to an overall SIR of 1.59 (95% confidence interval [CI] 1.53–1.64). Melanoma (n = 853, 28%) and female breast cancer (n = 594, 19%) were the most common types of second primary cancer in the study cohort. Relative risk of all second primary cancers combined among AYA patients was inversely associated with age and was highest within the period immediately after first diagnosis irrespective of age group; for example, patients aged 15–24 at first diagnosis recorded more than four times as many second primary cancers than expected within 2 years of their first cancer (SIR = 4.40, 95% CI 2.83–6.82). Conclusions: Detailed data on second primary cancers among AYA cancer survivors are important in promoting increased awareness and to inform the development of targeted prevention and surveillance strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluates the occurrence of second primary neoplasms (SPNs) in individuals with a history of melanoma (MM) and identify factors that increase the risk in our population. A prospective cohort study was conducted, involving 529 MM survivors from January 2005 to August 2021. Among the 529 patients, 89 were diagnosed with SPNs, with 62 being skin tumors and 37 being solid organ tumors. The estimated probability of developing SPNs after MM diagnosis was found to increase over time, reaching 4.1% at 1 year, 11% at 5 years, and 19% at 10 years. Several factors were significantly associated with a higher risk of SPNs, including older age, primary MM location on the face or neck, and the histologic subtype of lentigo maligna MM. We conclude that individuals with primary MM located on the face and neck, as well as those with the histological subtype of lentigo maligna-MM, have a higher risk of developing SPNs. Age also independently influences the risk. Understanding these risk factors can assist in developing MM guidelines that provide specific follow-up recommendations for individuals at the highest risk. (1) Introduction: The association between melanoma (MM) and the occurrence of second primary neoplasms (SPNs) has been extensively studied, with reported incidence rates ranging from 1.5% to 20%. This study aims to evaluate the occurrence of SPNs in patients with a history of primary MM and to describe the factors that make the risk higher in our population. (2) Material and Methods: We conducted a prospective cohort study and calculated the incidence rates and relative risks (RR) for the development of different SPNs in 529 MM survivors from 1 January 2005 to 1 August 2021. Survival and mortality rates were obtained, and the Cox proportional hazards model was used to determine the demographic and MM-related factors that influence the overall risk. (3) Results: Among the 529 patients included, 89 were diagnosed with SPNs (29 prior to MM diagnosis, 11 synchronous, and 49 after MM), resulting in 62 skin tumors and 37 solid organ tumors. The estimated probability of developing SPNs after MM diagnosis was 4.1% at 1 year, 11% at 5 years, and 19% at 10 years. Older age, primary MM location on the face or neck, and histologic subtype of lentigo maligna mm were significantly associated with a higher risk of SPNs. (4) Conclusions: In our population, the risk of developing SPNs was higher in patients with primary MM located on the face and neck and with the histological subtype of lentigo maligna-MM. Age also independently influences the risk. Understanding these hazard factors can aid in the development of MM guidelines with specific follow-up recommendations for individuals with the highest risk. [ABSTRACT FROM AUTHOR]

Metachronous carcinoma at the colostomy site is very rare after abdominoperineal resection. A 53-year-old male patient underwent an abdominoperineal resection 6 years earlier for rectal cancer developed metachronous carcinoma at the site of stoma. A portion of the colon, including the stoma and the surrounding skin, was resected and a new stoma was created in the transverse colon. Although the occurrence of carcinoma at the stoma site is a rare condition, careful observation for the stoma and colonoscopy for surveillance are necessary.

Background: Despite obtaining a good prognosis and long life expectancy, survivors of thyroid cancer can nevertheless develop subsequent primary cancer (SPC). We investigated the risk and types of SPC in patients with thyroid cancer and compared them with subjects without thyroid cancer history (controls). Methods: We conducted a nationwide, population-based, retrospective cohort study based on the Korean National Health Insurance Database. A total of 432,654 patients diagnosed with thyroid cancer between 2004 and 2019 were 1:1 matched with controls for age, sex, income, and region of residence. The hazard ratios (HR) and 95% confidence intervals (CI) of SPC were estimated using Cox proportional hazard models. Results: In total, 78,584 (18.2%) patients with thyroid cancer and 49,979 (11.6%) controls were diagnosed with SPCs over a mean follow-up of 6.9 years. Patients with thyroid cancer had a higher risk of SPC at any site (adjusted HR, 1.62; 95% CI, 1.60–1.64) than the controls. The risk of SPCs was particularly high for patients diagnosed with thyroid cancer at a younger age (Conclusions: Medical caregivers should consider the long-term follow-up of patients with thyroid cancer and discuss the risk of SPC, especially if they complain of cancer-related symptoms.

Purpose This study aimed to investigate whether MOS methylation can be useful for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms. Materials and Methods From 2012 to 2017, 294 patients were prospectively enrolled after endoscopic resection of gastric dysplasia (n=171) or early gastric cancer (n=123). When Helicobacter pylori was positive, eradication therapy was performed. Among them, 124 patients completed the study protocol (follow-up duration > 3 years or development of metachronous recurrence during the follow-up). Methylation levels of MOS were measured at baseline using quantitative MethyLight assay from the antrum. Results Median follow-up duration was 49.9 months. MOS methylation levels at baseline were not different by age, sex, and current H. pylori infection, but they showed a weak correlation with operative link on gastritis assessment (OLGA) or operative link on gastric intestinal metaplasia assessment (OLGIM) stages (Spearman's ρ=0.240 and 0.174, respectively; p < 0.05). During the follow-up, a total of 20 metachronous gastric neoplasms (13 adenomas and 7 adenocarcinomas) were developed. Either OLGA or OLGIM stage was not useful in predicting the risk for metachronous recurrence. In contrast, MOS methylation high group (≥ 34.82%) had a significantly increased risk for metachronous recurrence compared to MOS methylation low group (adjusted hazard ratio, 4.76; 95% confidence interval, 1.54 to 14.79; p=0.007). Conclusion MOS methylation can be a promising marker for predicting metachronous recurrence after endoscopic resection of gastric neoplasms. To confirm the usefulness of MOS methylation, validation studies are warranted in the future (ClinicalTrials No. NCT04830618). [ABSTRACT FROM AUTHOR]

A 42‐year‐old female patient with intellectual disability was presented to us as a newly diagnosed case of thymoma. She was identified as a case of multiple primary cancers, including adenocarcinoma of the rectum, carcinoma of the breast, and mediastinal thymoma, in a 15‐year period, who underwent chemotherapy, radiotherapy, and surgical resection. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long‐term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.

Abstract A 42‐year‐old female patient with intellectual disability was presented to us as a newly diagnosed case of thymoma. She was identified as a case of multiple primary cancers, including adenocarcinoma of the rectum, carcinoma of the breast, and mediastinal thymoma, in a 15‐year period, who underwent chemotherapy, radiotherapy, and surgical resection.

Objectives: The natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is still largely unknown. Since reports of second primary tumors (SPTs) in patients with HPV-related OPSCCs are increasing, a multifocal HPV infection, hinting a «virus-induced field effect», has been hypothesized. This study aimed to investigate the HPV-prevalence in normal appearing oropharyngeal tissue in patients with OPSCCs. Materials and Methods: 49 OPSCC patients undergoing panendoscopy were prospectively enrolled. Tumor specimens and biopsies of normal appearing oropharyngeal tissue adjacent to and distant from the index OPSCC underwent histopathological examination, p16INK4A immunohistochemical staining, HPV DNA and mRNA-detection. Patient characteristics and follow-up data on SPTs were obtained. Results: 26 of 49 (53%) OPSCC were positive for HPV DNA and p16INK4A. HPV mRNA was detected in 23 of 26 (88%) of these tumor samples. HPV DNA was detected in 36% adjacent mucosa and in 17% distant mucosa samples and only in patients with an HPV-related index OPSCC. HPV mRNA could not be detected in tumor-free distant and adjacent mucosa samples. No evidence of association between HPV detection in normal appearing mucosa and development of second primary tumors was found. Conclusions: HPV was detectable but not transcriptionally active in adjacent/distant tumor-free oropharyngeal tissue. This suggests that a multifocal HPV infection, hinting a «virus-induced fielcd cancerization», may not be pertaining to HPV-related OPSCC. [ABSTRACT FROM AUTHOR]

ObjectivesThe natural history of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is still largely unknown. Since reports of second primary tumors (SPTs) in patients with HPV-related OPSCCs are increasing, a multifocal HPV infection, hinting a «virus-induced field effect», has been hypothesized. This study aimed to investigate the HPV-prevalence in normal appearing oropharyngeal tissue in patients with OPSCCs.Materials and Methods49 OPSCC patients undergoing panendoscopy were prospectively enrolled. Tumor specimens and biopsies of normal appearing oropharyngeal tissue adjacent to and distant from the index OPSCC underwent histopathological examination, p16INK4A immunohistochemical staining, HPV DNA and mRNA-detection. Patient characteristics and follow-up data on SPTs were obtained.Results26 of 49 (53%) OPSCC were positive for HPV DNA and p16INK4A. HPV mRNA was detected in 23 of 26 (88%) of these tumor samples. HPV DNA was detected in 36% adjacent mucosa and in 17% distant mucosa samples and only in patients with an HPV-related index OPSCC. HPV mRNA could not be detected in tumor-free distant and adjacent mucosa samples. No evidence of association between HPV detection in normal appearing mucosa and development of second primary tumors was found.ConclusionsHPV was detectable but not transcriptionally active in adjacent/distant tumor-free oropharyngeal tissue. This suggests that a multifocal HPV infection, hinting a «virus-induced fielcd cancerization», may not be pertaining to HPV-related OPSCC.

BackgroundIn the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers.MethodsThe authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined.ResultsA cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers.ConclusionsNearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. © 2016 American Cancer Society.

Abstract Background The organisation of cancer follow-up is under scrutiny in many countries, and general practice is suggested to become more involved. A central focus is timely detection of recurring previous cancer and new second primary cancer. More knowledge on the patient pathway before cancer recurrence and second primary cancer is warranted to ensure the best possible organisation of follow-up. We aimed to describe the healthcare utilisation in the year preceding a diagnosis of cancer recurrence or second primary cancer. Methods This nationwide register study comprises patients diagnosed with bladder, breast, colorectal, endometrial, lung, malignant melanoma and ovarian cancer in Denmark in 2008–2016. The frequency of healthcare contacts during the 12 months preceding a cancer recurrence or second primary cancer was estimated and compared to the frequency of cancer survivors in cancer remission. The main analyses were stratified on sex and healthcare setting. Furthermore, two sub-analyses were stratified on 1) sex, healthcare setting and age group and on 2) sex, healthcare setting and comorbidity status. Results The study population consisted of 7832 patients with recurrence and 2703 patients with second primary cancer. On average, the patients were in contact with general practice one time per month in the 12th month preceding a new cancer diagnosis (recurrence or second primary cancer). Increasing contact rates were seen from 7 months before diagnosis in general practice and from 12 months before diagnosis in hospitals. This pattern was more pronounced in patients with cancer recurrence, younger patients and patients with no comorbidity. For instance, the contact rate ratios for hospital contacts in non-comorbid women with recurrence demonstrated 30% more contacts in the 12th month before recurrence and 127% more contacts in the 2nd month before recurrence. Conclusions The results show that cancer survivors are already seen in general practice on a regular basis. The increasing contact rates before a diagnosis of cancer recurrence or second primary cancer indicate that a window of opportunity exists for more timely diagnosis; this is seen in both general practice and in hospitals. Thus, cancer survivors may benefit from improvements in the organisation of cancer follow-up.

Background: Patients with hematological malignancies face an increased risk of developing second primary neoplasms due to various factors, including immune system compromise and chemotherapy-related effects. However, the incidence and associated risk factors in older patients remain poorly understood. This study aimed to assess the incidence, identify risk factors, and evaluate their impact on survival outcomes among older patients with hematological malignancies., Methods: This retrospective single-center study analyzed data from 163 patients, focusing on the occurrence of second primary neoplasms. Cumulative incidence rates were calculated, and risk factor analysis was conducted using a competing risk model., Results: Among 124 eligible patients with a total follow-up duration of 572.57 person-years, the incidence rate of second primary neoplasms was 15.72/1000 person-years. The standardized incidence ratio (SIR) was 0.81 (95% confidence interval [CI] [0.39-1.48], P  = 0.518). History of radiotherapy emerged as a significant risk factor (sub-distribution hazard ratio [SHR] = 21.61 [2.81-166.14], P  = 0.003), whereas regular natural killer (NK) cell infusion was associated with reduced risk (SHR = 3.25 e-8 [9.81 e-9-1.08 e-7], P ＜ 0.001)., Conclusions: These findings underscore the importance of informing older patients with hematological malignancies about the long-term risks of second primary neoplasms. Healthcare providers should carefully weigh risk factors when formulating treatment strategies. The results are valuable for investigating the fundamental principles underlying the occurrence and progression of second primary neoplasms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

BackgroundMost gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry.MethodsPatients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population.ResultsThere were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis.ConclusionsThis is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

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Martin Lovecek,1,* Marketa Janatova,2,* Pavel Skalicky,1 Tomas Zemanek,3 Roman Havlik,1 Jiri Ehrmann,4 Ondrej Strouhal,3 Petra Zemankova,2 Klara Lhotova,2 Marianna Borecka,2 Jana Soukupova,2 Hana Svebisova,3 Pavel Soucek,5 Viktor Hlavac,5 Zdenek Kleibl,2 Cestmir Neoral,1 Bohuslav Melichar,3 Beatrice Mohelnikova-Duchonova3 1Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 2Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; 3Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic; 4Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University Olomouc, University Hospital Olomouc, Olomouc, Czech Republic; 5Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen Czech Republic *These authors contributed equally to this work Background: The principal aim of this report was to study second primary malignant neoplasms (SMNs) in long-term survivors of pancreatic ductal adenocarcinoma (PDAC) with regard to the germline genetic background.Patients and methods: A total of 118 PDAC patients after a curative-intent surgery who were treated between 2006 and 2011 were analyzed. Of the 22 patients surviving for >5 years, six went on to develop SMNs. A genetic analysis of 219 hereditary cancer-predisposition and candidate genes was performed by targeted next-generation sequencing in germline DNA from 20 of these patients.Results: Of all the radically resected PDAC patients, six patients went on to subsequently develop SMNs, which accounted for 27% of the long-term survivors. The median time to diagnosis of SMNs, which included two cases of rectal cancer, and one case each of prostate cancer, malignant melanoma, breast cancer, and urinary bladder cancer, was 52.5 months. At the time of analysis, none of these patients had died as a result of PDAC progression. We identified four carriers of germline pathogenic mutations in 20 analyzed long-term survivors. One carrier of the CHEK2 mutation was found among four analyzed patients who developed SMNs. Of the remaining 16 long-term PDAC survivors, 3 patients (19%) carried germline mutation(s) in the MLH1+ ATM, CHEK2, and RAD51D gene, respectively.Conclusion: This retrospective analysis indicates that SMNs in PDAC survivors are an important clinical problem and may be more common than has been acknowledged to be the case. In patients with good performance status, surgical therapy should be considered, as the SMNs often have a favorable prognosis. Keywords: pancreatic ductal adenocarcinoma, second primary neoplasms, subsequent malignant neoplasm, hereditary cancer genes, long-term survivors, surgical treatment

Purpose A prior history of breast cancer is a risk factor for the subsequent development of primary peritoneal, epithelial ovarian, and fallopian tubal (POFT) cancers. This study aimed to estimate the incidence of secondary POFT malignancy in breast cancer patients and the clinical outcomes of primary and secondary POFT cancer. Materials and Methods We searched the Korea Central Cancer Registry to find patients with primary and secondary POFT cancer who had breast cancer in 1999-2017. The incidence rate and standardized incidence ratio were calculated. Additionally, we compared the overall survival of patients with primary and secondary POFT cancer. Results Based on the age-standardized rate, the incidence of second primary POFT cancer after breast cancer was 0.0763 per 100,000 women, which increased in Korea between 1999 and 2017. Among the 30,366 POFT cancer patients, 25,721 were primary POFT cancer only, and 493 had secondary POFT cancer after a breast cancer diagnosis. Second primary POFT cancer patients were older at the time of diagnosis (55 vs. 53, p < 0.001) and had a larger proportion of serous histology (68.4% vs. 51.2%, p < 0.001) than patients with primary POFT. There were no differences between the two groups in tumor stage at diagnosis. The 5-year overall survival rates were 60.2% and 56.3% for primary and secondary POFT cancer, respectively (p=0.216). Conclusion The incidence of second primary POFT cancer after breast cancer increased in Korea between 1999 and 2017. Besides, second primary POFT cancer patients were diagnosed at older ages and had more serous histology. [ABSTRACT FROM AUTHOR]

Childhood cancer patients are at increased risk of second primary neoplasms (SPNs). We assessed incidence and risk factors for early SPNs with a focus on cancer predisposition syndromes (CPSs). This cohort study used data from the Swiss Childhood Cancer Registry. We included patients with first primary neoplasms (FPNs) diagnosed before age 21 years from 1986 to 2015 and identified SPNs occurring before age 21. We calculated standardised incidence ratios (SIRs) and absolute excess risks (AERs) using Swiss population cancer incidence data, and cumulative incidence of SPNs. We calculated hazard ratios (HRs) of risk factors for SPNs using Fine and Gray competing risk regression. Among 8074 childhood cancer patients, 304 (4%) were diagnosed with a CPS and 94 (1%) developed early SPNs. The incidence of SPNs was more than 10-fold higher in childhood cancer patients than the incidence of neoplasms in the general population (SIR = 10.6, 95% confidence interval [CI]: 8.7–13.1) and the AER was 179/100,000 person-years (CI: 139–219). Cumulative incidence of SPNs 20 years after FPN diagnosis was 23% in patients with CPSs (CI: 12–41%) and 2.7% in those without (CI: 2.0–3.6%). Risk factors for SPNs were CPSs (HR = 7.8, CI: 4.8–12.7), chemotherapy (HR = 2.2, CI: 1.1–4.6), radiotherapy (HR = 1.9, CI = 1.2–2.9), haematopoietic stem cell transplantation (HR = 1.8, CI: 1–3.3), and older age (15–20 years) at FPN diagnosis (HR = 1.9, CI: 1.1–3.2). CPSs are associated with a high risk of SPNs before age 21 years. Identification of CPSs is important for appropriate cancer surveillance and targeted screening. Image 1 • The incidence of second primary neoplasms (SPNs) before age 21 years was 10-fold higher after childhood cancer compared to the general population. • Cancer predisposition syndromes (CPSs) were the strongest predictor of SPNs. • The cumulative incidence of SPNs was 23% (95%CI 12–41%) in CPSs after 20 years of follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Patients with testicular non-seminomatous germ cell tumors in the modern cisplatin-based chemotherapy era show favorable outcomes, yielding survivors exposed to increased risk of second malignant neoplasms. The carcinogenic effects of cisplatin were well established, and its side effects had shown close connections with the urinary system. The study aimed to evaluate how the characteristics of the primary testicular nonseminoma are associated with urological second malignant neoplasms and survival outcomes. Methods: Using the Surveillance, Epidemiology and End Results database, standardized incidence ratios (SIR) for three major urological tumors including kidney, bladder, and prostate cancer were calculated for 10,734 patients with testicular nonseminoma from 1975 to 2016. The survival analyses were performed using the Kaplan–Meier method and log-rank test, risk factors for overall survival were determined by Cox regression. Results: We identified a total of 197 patients with secondary urological neoplasms. Patients with previous testicular nonseminoma had elevated risk of kidney cancer (SIR 2.13, 95% CI 1.59–2.79), bladder cancer (SIR 1.47, 95% CI 1.07–1.59), and decreased risks of prostate cancer (SIR 0.75, 95% CI 0.61–0.91) compared with the general population. Patients diagnosed with testicular nonseminoma had favorable prognosis with 10-year overall survival reaching 91.8%, and patients with urological second malignant neoplasms showed better prognoses than patients with other second malignant neoplasms (log-rank P < 0.001). Conclusion: Testicular nonseminoma survivors showed higher risks of kidney and bladder cancer associated with chemotherapy and decreased risk of prostate cancer. The prognosis of urological second neoplasms was better than other tumor origins. [ABSTRACT FROM AUTHOR]

IntroductionAll colorectal cancer (CRC) survivors have an increased risk of developing second primary malignancies (SPMs). The association between diabetes mellitus (DM) and the risk of cancer is well known. However, the role of DM and its therapy in the development of SPMs in CRC patients is not well described.MethodsIn this single-institutional retrospective analysis we identified 1,174 colorectal carcinoma patients, median follow-up 10.1 years, (median age 63 years, 724 men). All patients over 18 years with histologically confirmed CRC who were admitted in the period 1.1. 2003- 31.12.2013 and followed-up till 31.12. 2018 at the Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. The exclusion criteria were CRC diagnosed at autopsy, lost to follow-up and high risk of development of SPMs due to hereditary cancer syndrome. Tumours are considered multiple primary malignancies if arising in different sites and/or are of a different histology or morphology group. Comparisons of the basic characteristics between the patients with SPM and the patients without SPM were performed as well as comparison of the occurrence of SPMs by the site of diagnosis between the DM and non-DM cohorts and survival analyses.ResultsA SPM was diagnosed in 234 (20%) patients, DM in 183 (15%) patients. DM was diagnosed in 22.6% of those with SPM vs. in 13.8% of those without SPM (p=0.001). The most common types of SPMs in DM patients were other CRC, kidney, lung, bladder and nonmelanoma skin cancer, but only carcinoma of the liver and bile duct tracts was significantly more common than in the group without DM. Although breast cancer was the second most common in the group with DM, its incidence was lower than in the group without DM, as well as prostate cancer. A significantly higher incidence of SPMs was found in older CRC patients (≥ 65 years) and in those with lower stage colon cancer and DM. No significant difference in DM treatment between those with and without a SPM was observed including analysis of type of insulin.ConclusionCRC patients with diabetes mellitus, especially those with older age, and early stages of colon cancer, should be screened for second primary malignancies more often than the standard population. Patients without DM have longer survival. According to the occurrence of the most common second malignancies, a clinical examination, blood count, and ultrasound of the abdomen is appropriate, together with standard breast and colorectal cancer screening, and lung cancer screening under certain conditions, and should be recommended in CRC survivors especially in patients with intercurrent DM, however the necessary frequency of screening remains unclear.

Introduction: All colorectal cancer (CRC) survivors have an increased risk of developing second primary malignancies (SPMs). The association between diabetes mellitus (DM) and the risk of cancer is well known. However, the role of DM and its therapy in the development of SPMs in CRC patients is not well described. Methods: In this single-institutional retrospective analysis we identified 1,174 colorectal carcinoma patients, median follow-up 10.1 years, (median age 63 years, 724 men). All patients over 18 years with histologically confirmed CRC who were admitted in the period 1.1. 2003- 31.12.2013 and followed-up till 31.12. 2018 at the Masaryk Memorial Cancer Institute (MMCI) were screened for eligibility. The exclusion criteria were CRC diagnosed at autopsy, lost to follow-up and high risk of development of SPMs due to hereditary cancer syndrome. Tumours are considered multiple primary malignancies if arising in different sites and/or are of a different histology or morphology group. Comparisons of the basic characteristics between the patients with SPM and the patients without SPM were performed as well as comparison of the occurrence of SPMs by the site of diagnosis between the DM and non-DM cohorts and survival analyses. Results: A SPM was diagnosed in 234 (20%) patients, DM in 183 (15%) patients. DM was diagnosed in 22.6% of those with SPM vs. in 13.8% of those without SPM (p=0.001). The most common types of SPMs in DM patients were other CRC, kidney, lung, bladder and nonmelanoma skin cancer, but only carcinoma of the liver and bile duct tracts was significantly more common than in the group without DM. Although breast cancer was the second most common in the group with DM, its incidence was lower than in the group without DM, as well as prostate cancer. A significantly higher incidence of SPMs was found in older CRC patients (≥ 65 years) and in those with lower stage colon cancer and DM. No significant difference in DM treatment between those with and without a SPM was observed including analysis of type of insulin. Conclusion: CRC patients with diabetes mellitus, especially those with older age, and early stages of colon cancer, should be screened for second primary malignancies more often than the standard population. Patients without DM have longer survival. According to the occurrence of the most common second malignancies, a clinical examination, blood count, and ultrasound of the abdomen is appropriate, together with standard breast and colorectal cancer screening, and lung cancer screening under certain conditions, and should be recommended in CRC survivors especially in patients with intercurrent DM, however the necessary frequency of screening remains unclear. [ABSTRACT FROM AUTHOR]

Purpose The epidemiology of B-cell non-Hodgkin lymphoma (BNHL) in Asia is not well described, and rates of second primary malignancies (SPM) in these patients are not known. We aimed to describe temporal changes in BNHL epidemiology and SPM incidence in Korea. Materials and Methods A retrospective cohort study used claims data from the National Health Insurance Service that provides universal healthcare coverage in Korea. Newly diagnosed patients aged at least 19 years with a confirmed diagnosis of one of six BNHL subtypes (diffuse large cell B-cell lymphoma [DLBCL], small lymphocytic and chronic lymphocytic [CLL/SLL], follicular lymphoma [FL], mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], and lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia [WM]) during the period 2006-2015 were enrolled and followed up until death, dis-enrolment, or study end, whichever occurred first. Patients with pre-existing primary cancers prior to the diagnosis of BNHL were excluded. Results A total of 19,500 patients with newly diagnosed BNHL were identified out of 27,866 with non-Hodgkin lymphoma (NHL). DLBCL was the most frequently diagnosed subtype (41.9%- 48.4% of NHL patients annually, 2011-2015). Standardized incidence of the six subtypes studied per 100,000 population increased from 5.74 in 2011 to 6.96 in 2015, with most increases in DLBCL, FL, and MZL. The incidence (95% confidence interval) of SPM per 100 person-years was 2.74 (2.26-3.29) for CLL/SLL, 2.43 (1.57-3.58) for MCL, 2.41 (2.10-2.76) for MZL, 2.23 (2.07-2.40) for DLBCL, 1.97 (1.61-2.38) for FL, and 1.41 (0.69-2.59) for WM. Conclusion BNHL has been increasingly diagnosed in Korea. High rates of SPM highlight the need for continued close monitoring to ensure early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long‐lasting increased risk for noncervical high‐risk human papillomavirus (hrHPV)‐related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post‐treatment. Cases of noncervical hrHPV‐related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person‐years of follow‐up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV‐related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow‐up and prophylactic hrHPV vaccination are warranted. What's new? Most cervical and many anogenital cancer cases are high‐risk human papillomavirus (hrHPV) infection‐related. However, the risk of noncervical hrHPV‐related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3 (CIN3) remains poorly studied. This study found that women with recurrent CIN3 had an increased risk of developing non‐cervical hrHPV‐related (pre)malignancies compared to women without CIN3, with an incidence rate ratio (IRR) of 25.96. The IRR was 2.48 compared to women with a single episode of CIN3. Besides intensified cervical screening, women with recurrent CIN3 may thus benefit from increased awareness of other hrHPV‐related (pre)malignancies and adjuvant hrHPV‐vaccination to prevent noncervical hrHPV‐related cancers. [ABSTRACT FROM AUTHOR]

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33-6.24], P = 0.007) and multivariate (HR 2.98 [1.34-6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician's decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Purpose: The risk of being diagnosed with contralateral breast cancer (CBC) is an important health issue among breast cancer survivors. There is an increasing interest in the effect of lifestyle and reproductive factors on CBC risk, since these factors may partly be modifiable. We performed a systematic review and meta-analysis and aimed to evaluate the impact of lifestyle and reproductive factors on CBC risk in population-based breast cancer studies.Methods: The PubMed electronic database was searched up to 2nd November 2019, for relevant publications. Of the included studies, a meta-analysis per lifestyle or reproductive factor was performed.Results: Thirteen out of 784 publications were used for the meta-analysis. Body mass index (≥ 25 vs. < 25 kg/m2; RR = 1.22; 95% CI 1.01-1.47) was associated with increased CBC risk. The estimates for alcohol use (ever vs. never; RR = 1.15; 95% CI 1.02-1.31) and age at primiparity (≥ 25 vs. < 25 years; RR = 1.06; 95% CI 1.02-1.10) also showed an association with increased CBC risk. For parity (≥ 4 vs. nulliparous; RR = 0.56; 95% CI 0.42-0.76) and age at menopause (< 45 vs ≥ 45 years; RR = 0.79; 95% CI 0.67-0.93), results from two studies suggested a decreased CBC risk. We observed no association between CBC and smoking, age at menarche, oral contraceptive use, gravidity, breastfeeding, or menopausal status. Overall, the number of studies per risk factor was limited (n = 2-5).Conclusions: BMI is a modifiable risk factor for CBC. Data on the effect of other modifiable lifestyle and reproductive factors are limited. For better counseling of patients on lifestyle effects, more studies are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an increased risk of secondary primary malignancies (SPMs) after diffuse large B-cell lymphoma (DLBCL) treatment. Whether stage of DLBCL at diagnosis affects the subtypes of SPMs that occur has not been previously described.Methods: The Surveillance, Epidemiology, and End Results database was queried for patients aged >18 years diagnosed with primary DLBCL from 1973 to 2010 and categorized by early stage (ES) (stage I-II) or advanced stage (AS) (stage III-IV) disease. Differences in overall and location-specific SPM incidence by stage and time since diagnosis were assessed in 5-year intervals using a Fine-Gray hazards model. Overall survival was compared using the log-rank test. A Cox proportional hazards model was used to assess differences in survival.Results: In total, 26,038 patients with DLBCL were identified, including 14,724 with ES and 11,314 with AS disease. The median follow-up was 13.3 years. Overall, 13.0% of patients developed SPM, with a higher but nonsignificantly increased risk of SPM development in those who had ES disease compared with those who had AS disease (14% vs 11.6%; P = .14). During the first 5 years after diagnosis, patients who had ES disease had a higher risk of SPM than those who had AS disease, specifically colorectal, pancreas, breast, and prostate SPMs. During the period from 10 to 15 years after diagnosis, patients who had AS disease had a higher risk of SPM than those who had ES disease, specifically hematologic SPMs. Development of SPM was found to significantly increase the risk of death regardless of stage at diagnosis.Conclusions: In this large, population-based study, distinctly different subtypes and temporal patterns of SPM development were identified based on stage of DLBCL at diagnosis. The current study merits consideration of tailored site-specific and time-specific surveillance for patients with DLBCL according to stage and time interval since diagnosis. [ABSTRACT FROM AUTHOR]

A significant problem for long-term rectal cancer survivors may be the late toxicity of radiotherapy. It creates the possible risk of developing second primary malignancy and a theoretical decrease in overall survival. This study aimed to assess the influence of short-course preoperative radiotherapy in patients with locally advanced rectal cancer on overall survival, local recurrence rate, and second malignancy at 18-year follow-up. The rectal cancer trial was conducted in a single tertiary center between February 1992 and June 2006. A total of 389 patients with locally advanced rectal cancer (cT2-cT4, cN0/+, cM0) were included in the study. Preoperative radiotherapy was conducted in 148 patients and 241 patients underwent surgery alone. The propensity-matched group consisted of 105 patients operated on after radiotherapy and 105 controls. The number of local recurrences was 7 (6.7%) in the preoperative radiotherapy group and 22 (21%) in the surgery alone group (p = 0.016). The 18-year survival analysis showed no survival benefit in the preoperative radiotherapy group (38% versus 48%, p = 0.107) but improved recurrence-free survival (81% versus 58%, p = 0.001). The preoperative short-course radiotherapy significantly decreases the risk of local recurrence in locally advanced rectal cancer and may improve recurrence-free survival without an increased risk of second primary malignancy.

Purpose Clinicopathologic characteristics of patients with both thyroid and breast cancer during their lifetime were analyzed to investigate the association between the two malignancies according to the order of incidence. Methods A total of 405 patients who underwent surgery for breast and thyroid cancer at Severance Hospital between 1995 and 2014 were retrospectively selected and classified into 3 groups according to the order of incidence of the two cancers: simultaneous cancer (S), thyroid cancer followed by breast cancer (TB), and breast cancer followed by thyroid cancer (BT). Univariate analysis was conducted to compare parameters. Results S, TB, and BT groups were 166 (41.0%), 96 (23.7%), and 143 (35.3%) patients, respectively. In TB and BT groups, tumor size and surgical site for secondary cancer were smaller; therefore, adjuvant treatments were less frequently required for secondary cancer. ER positive rate was 77.1% in S, 75% in TB, and 63.7% in BT groups (P=0.027). The ratio of ER negative was higher in the group with BRAF mutation. Survival rate for index tumor was higher in order from TB, and BT, followed by S groups without statistical difference. Conclusion It is difficult to find a significant difference according to the order of occurrence except by screening test, and more studies are needed in the future. Establishing an appropriate screening program is important in order to detect secondary breast or thyroid cancer after surgery for thyroid or breast cancer.

Background: The prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known.Methods: A total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36).Results: By 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains.Conclusions: Late-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer is common and lethal, and can occur in survivors of previous cancers. We sought to describe the incidence and mortality attributable to second primary lung cancers (SPLC) among survivors of other cancers, and to identify survivors at highest risk.Methods: We identified adults diagnosed with a localized malignancy from non-pulmonary cancer sites from surveillance, epidemiology, and end results (SEER) data from 1992 to 2008. We explored factors associated with the incidence and death from SPLC using bivariable and multivariable models. Finally, we compared standardized incidence rates for SPLC in our cohort with the control arm of the National Lung Screening Trial (NLST), a randomized lung cancer screening trial.Results: We identified 1,450,837 survivors of non-pulmonary cancers, of whom 25,472 developed SPLC at a mean (SD) follow-up of 5.7 (3.6) years. Over half (57%) of patients with SPLC died of the disease. Survivors of cancer of the hypopharynx, oropharynx, tonsil, and larynx, experienced SPLC at standardized incidence rates which greatly exceeded that observed in the control arm of the NLST (572/100,000 person-years). Additionally, survivors of bladder and esophageal cancer had rates that approached the NLST control arm rate. Increasing age and being divorced/widowed/separated were independent risk factors for SPLC in most primary cancer types.Conclusion: The incidence of SPLC in survivors of certain primary cancers greatly exceeds the rate observed in the control arm of the NLST. Further study could help determine if screening for lung cancer in these cancer survivors could prevent death from lung cancer. [ABSTRACT FROM AUTHOR]

Aim: Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity‐modulated radiotherapy (IMRT). Methods: A retrospective review of 780 consecutive IMRT‐treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar‐year–specific cancer incidences from the Hong Kong Cancer Registry. Results: At a median follow‐up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in‐field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025–1.078] and smoking status (HR, 1.755; 95% CI, 1.002–3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37–2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow‐up. Conclusion: Substantial risk of SPT, especially for in‐field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the second primary cancers (SPCs) in patients with urothelial cancer (UC). Materials and Methods: The records of 2,339 patients whose UC was diagnosed between January 1974 and December 2012 were reviewed. All data about characteristics of patients, of UC and, of SPC was, recorded digitally. We investigated the prevalence and the type of second or higher order cancers, and the factors associated with SPC. Results: Total 260 patients (11.1%) had SPC, 14 had a third primary cancer and one had a fourth primary cancer. The most common SPC with UC was lung cancer (29.6%). Of all 260 with SPC, 64 (24.6%) had synchronous (within the 6 months) SPC, 120 (46.2%) had subsequent SPC and, 76 (29.2%) had antecedent SPC. The mean duration of SPC was 56 months in patients with subsequent SPC and 75.8 months in patients with antecedent SPC. The mean age at the time of diagnosis of UC was higher in patients with SPC. The ratio of male gender, body mass index, blood type, status of smoking and, occupational risk was similar in both groups. Total amount of smoking and the mean follow-up were higher in patients with SPC. Conclusions: The majority of the patients with UC have long life expectancy. In patients with UC, the risk of having another cancer is quite higher than normal population. The physicians managing patients with UC should look for SPC.

Purpose: As the population of breast cancer survivors increasing, concerns for second primary cancer has been grown. The most frequent second primary tumor after breast cancer diagnosis is contralateral breast cancer (CBC). CBC developed less than five years showed poor prognosis. However, in Korea, little is known about the clinical characteristics of CBC regarding diagnosis interval. Methods: We retrospectively reviewed medical records of the patients who diagnosed stage I-III breast cancer from three tertiary medical centers and identified CBC patients. We divided those patients into early-onset CBC (ECBC), which diagnosed within five years, and late-onset CBC (LCBC) which developed after five years since primary cancer. We also searched available published original articles regarding bilateral breast cancer in Korean population for comparison. Results: Between January 2003 and December 2013, a total of 3,695 patients were included. During follow up, 22 patients diagnosed as CBC. Mean age of ECBC (n=10) was 50.9±15.4 and that of LCBC (n=12) was 45.5±14.3. There were no significant difference between ECBC and LCBC in menopausal status, menarcheal age, family history of breast cancer, clinical stage, and pathologic characteristics. ECBC was related worse disease-free survival than LCBC (P=0.017). With meta-analysis of published reports in Korean population, the incident rate calculated from person-month was 0.06. Conclusion: ECBC showed poor prognosis than LCBC with cut-off at five years since diagnosis of primary breast cancer, and it was consistent with Western reports. Intensive treatment might be needed in those patients with ECBC.

Background/aims: Metachronous gastric cancer (MGC) can occur after endoscopic resection for gastric cancer. Further studies on factors other than Helicobacter pylori infection are needed. This systematic review and meta-analysis aimed to evaluate risk factors for metachronous recurrence of endoscopically resected gastric cancer., Methods: We searched medical literature published by February 2023 and identified patients with MGC after endoscopic resection for gastric cancer. The occurrence of MGC and the presence of intestinal metaplasia (IM), severe atrophic gastritis (AG), and H. pylori infection were quantitatively analyzed., Results: We identified 2,755 patients from nine cohort studies who underwent endoscopic resection for gastric cancer by 2018. Those with severe AG or presence of IM had a significantly higher incidence of MGC than those without (RR 2.00, 95% CI 1.35-2.98, I2 = 52% for severe atrophy on antrum; RR 7.08, 95% CI 3.63-13.80, I2 = 0% for antral IM). Absolute risk difference of MGC occurrence was 7.1% in those with severe AG and 9.2% in those with IM. The difference in incidence rate per 1,000 person-years was 17.5 person-years for those with severe AG and 24.7 person-years for those with IM. However, H. pylori eradication did not significantly affect the occurrence of MGC (RR 1.18, 95% CI 0.88-1.59, I2 = 10%)., Conclusion: Gastric cancer patients with severe AG or presence of IM had a 2.0-fold or 7.0-fold higher risk of MGC occurrence after endoscopic resection than those without, respectively. They need more stringent follow-up to monitor MGC occurrences (CRD42023410940).