Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System.

ABSTRACT: Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.

Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study.

BACKGROUND & AIMS: The study investigated the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection of gastric dysplasia. METHODS: Patients who received endoscopic resection for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. RESULTS: Gastric dysplasia in 69,722 patients was treated with endoscopy, and 49.5% were administered H pylori therapy. During the median 5.6 years of follow-up, gastric cancer developed in 2406 patients and metachronous gastric neoplasms developed in 3342 patients. Receiving H pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.80-0.96). H pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR, 0.76; 95% CI, 0.70-0.82). Furthermore, H pylori therapy showed a prominent protective effect for late-onset gastric cancer development at ≥3 years (aHR, 0.84; 95% CI, 0.75-0.94) and ≥5 years (aHR, 0.80; 95% CI, 0.68-0.95). CONCLUSIONS: In this nationwide cohort, H pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.

BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis.

In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.

Risk of male breast cancer after Hodgkin lymphoma.

Female survivors of Hodgkin lymphoma (HL) treated with chest radiotherapy have a strongly increased risk of breast cancer (BC), but the treatment-specific BC risk in male survivors of HL has not been evaluated. We assessed BC risk in a cohort of 3077 male survivors of 5-year HL treated at age ≤51 years in 20 Dutch hospitals between 1965 and 2013. We estimated standardized incidence ratios (SIRs), absolute excess risks per 10 000 person-years, and cumulative BC incidences. After a 20-year median follow-up, we observed 8 cases of male with BC. Male survivors of HL experienced a 23-fold (95% confidence interval [CI], 10.1-46.0) increased BC risk compared with the general population, representing 1.6 (95% CI, 0.7-3.3) excess BC incidences per 10 000 person-years. The 20- and 40-year cumulative BC incidences after HL treatment were 0.1% (95% CI, 0.02-0.3) and 0.7% (95% CI, 0.3-1.4), respectively. Treatment with chest radiotherapy without alkylating chemotherapy yielded a strongly increased SIR (20.7; 95% CI, 2.5-74.8), which was not significantly different for chest radiotherapy and alkylating chemotherapy (41.1; 95% CI, 13.4-96.0). Males treated with chest radiotherapy and anthracyclines had an SIR of 48.1 (95% CI, 13.1-123.1). Two patients died from BC (median follow-up, 4.7 years). To ensure early diagnosis and treatment, clinicians should be alert to BC symptoms in male survivors of HL.

Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Survival difference between secondary and de novo acute myeloid leukemia by age, antecedent cancer types, and chemotherapy receipt.

BACKGROUND: This study compared the survival of persons with secondary acute myeloid leukemia (sAML) to those with de novo AML (dnAML) by age at AML diagnosis, chemotherapy receipt, and cancer type preceding sAML diagnosis. METHODS: Data from Surveillance, Epidemiology, and End Results 17 Registries were used, which included 47,704 individuals diagnosed with AML between 2001 and 2018. Multivariable Cox proportional hazards regression was used to compare AML-specific survival between sAML and dnAML. Trends in 5-year age-standardized relative survival were examined via the Joinpoint survival model. RESULTS: Overall, individuals with sAML had an 8% higher risk of dying from AML (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.05-1.11) compared to those with dnAML. Disparities widened with younger age at diagnosis, particularly in those who received chemotherapy for AML (HR, 1.14; 95% CI, 1.10-1.19). In persons aged 20-64 years and who received chemotherapy, HRs were greatest for those with antecedent myelodysplastic syndrome (HR, 2.04; 95% CI, 1.83-2.28), ovarian cancer (HR, 1.91; 95% CI, 1.19-3.08), head and neck cancer (HR, 1.55; 95% CI, 1.02-2.36), leukemia (HR, 1.45; 95% CI, 1.12-1.89), and non-Hodgkin lymphoma (HR, 1.42; 95% CI, 1.20-1.69). Among those aged ≥65 years and who received chemotherapy, HRs were highest for those with antecedent cervical cancer (HR, 2.42; 95% CI, 1.15-5.10) and myelodysplastic syndrome (HR, 1.28; 95% CI, 1.19-1.38). The 5-year relative survival improved 0.3% per year for sAML slower than 0.86% per year for dnAML. Consequently, the survival gap widened from 7.2% (95% CI, 5.4%-9.0%) during the period 2001-2003 to 14.3% (95% CI, 12.8%-15.8%) during the period 2012-2014. CONCLUSIONS: Significant survival disparities exist between sAML and dnAML on the basis of age at diagnosis, chemotherapy receipt, and antecedent cancer, which highlights opportunities to improve outcomes among those diagnosed with sAML.

Risk of subsequent gliomas and meningiomas among 69,460 5-year survivors of childhood and adolescent cancer in Europe: the PanCareSurFup study.

BACKGROUND: Childhood cancer survivors are at risk of subsequent gliomas and meningiomas, but the risks beyond age 40 years are uncertain. We quantified these risks in the largest ever cohort. METHODS: Using data from 69,460 5-year childhood cancer survivors (diagnosed 1940-2008), across Europe, standardized incidence ratios (SIRs) and cumulative incidence were calculated. RESULTS: In total, 279 glioma and 761 meningioma were identified. CNS tumour (SIR: 16.2, 95% CI: 13.7, 19.2) and leukaemia (SIR: 11.2, 95% CI: 8.8, 14.2) survivors were at greatest risk of glioma. The SIR for CNS tumour survivors was still 4.3-fold after age 50 (95% CI: 1.9, 9.6), and for leukaemia survivors still 10.2-fold after age 40 (95% CI: 4.9, 21.4). Following cranial radiotherapy (CRT), the cumulative incidence of a glioma in CNS tumour survivors was 2.7%, 3.7% and 5.0% by ages 40, 50 and 60, respectively, whilst for leukaemia this was 1.2% and 1.7% by ages 40 and 50. The cumulative incidence of a meningioma after CRT in CNS tumour survivors doubled from 5.9% to 12.5% between ages 40 and 60, and in leukaemia survivors increased from 5.8% to 10.2% between ages 40 and 50. DISCUSSION: Clinicians following up survivors should be aware that the substantial risks of meningioma and glioma following CRT are sustained beyond age 40 and be vigilant for symptoms.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk.

BACKGROUND: Lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors. METHODS: We (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied. RESULTS: The adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53-3.49) for females and 1.15 (95% CI 1.03-1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes. CONCLUSIONS: Our proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Subsequent primary neoplasms after childhood cancer therapy - design and description of the German nested case-control study STATT-SCAR.

BACKGROUND: Subsequent primary neoplasms (SPN) are among the most severe late effects and the second most frequent cause of death in childhood cancer patients. In this paper we introduce method and properties of the STATT-SCAR study (Second Tumor After Tumor Therapy, Second Cancer After Radiotherapy), which is a joint nested matched case-control study to evaluate the impact of chemotherapy (STATT) as well as radiotherapy (SCAR) on the risk of developing a SPN. METHODS: Based on the cohort of the German childhood cancer registry (GCCR), we selected patients diagnosed with a first neoplasm before age 15 or younger between 1980 and 2014. We selected those with a SPN at least half a year after the first neoplasm, and matched up to four controls to each case. Therapy data were acquired from various sources, including clinical study centers and treating hospitals. To analyze the impact of radiotherapy, organ doses were estimated by using reconstructed treatment plans. The effect of chemotherapy was analyzed using substance groups summarized after isotoxic dose conversion. RESULTS: 1244 cases with a SPN were identified and matched with 4976 controls. Treatment data were acquired for 83% of all match groups (one case and at least one control). Based on preliminary analyses, 98% of all patients received chemotherapy and 54% of all patients were treated with radiotherapy. CONCLUSIONS: Based on our data, detailed analyses of dose response relationships and treatment element combinations are possible, leading to a deeper insight into SPN risks after cancer treatments. TRIAL REGISTRATION: The study is registered at the German clinical trial register (DRKS) under number DRKS00017847 [45].

Variation in patterns of second primary malignancies across U.S. race and ethnicity groups: a Surveillance, Epidemiology, and End Results (SEER) analysis.

PURPOSE: One in six incident cancers in the U.S. is a second primary cancer (SPC). Although primary cancers vary considerably by race and ethnicity, little is known about the population-based occurrence of SPC across these groups. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) 12 data and relative to the general population, we calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPC among 2,457,756 Hispanics, non-Hispanic Asian American/Pacific Islanders (NHAAPI), non-Hispanic black (NHB), and non-Hispanic whites (NHW) cancer survivors aged 45 years or older when diagnosed with a first primary cancer (FPC) from 1992 to 2015. RESULTS: The risk of second primary bladder cancer after first primary prostate cancer was higher than expected in Hispanic (SIR = 1.18, 95% CI: 1.01-1.38) and NHAAPI (SIR = 1.41, 95% CI: 1.20-1.65) men than NHB and NHW men. Among women with a primary breast cancer, Hispanic, NHAAPI, and NHB women had a nearly 1.5-fold higher risk of a second primary breast cancer, while NHW women had a 6% lower risk. Among men with prostate cancer whose SPC was diagnosed 2 to <12 months, NHB men were at higher risk for colorectal cancer and Hispanic and NHW men for non-Hodgkin's lymphoma. In the same time frame for breast cancer survivors, Hispanic and NHAAPI women were significantly more likely than NHB and NHW women to be diagnosed with a second primary lung cancer. CONCLUSION: Future studies of SPC should investigate the role of shared etiologies, stage of diagnosis, treatment, and lifestyle factors after cancer survival across different racial and ethnic populations.

Long-Term Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy.

PURPOSE: Second malignancy is a rare but potentially lethal event after prostate brachytherapy, but data remain scarce on its long-term risk. The objective of this study is to estimate the number of pelvic second malignancies following brachytherapy compared to radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively reviewed patients treated with low-dose 125I brachytherapy and RP in British Columbia from 1999 to 2010. Kaplan-Meier estimates for pelvic (bladder and rectum), invasive pelvic, any second malignancy, and death from any second malignancy were assessed. Cox multivariable analyses were performed adjusting for initial treatment type, age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking history. RESULTS: Two thousand three hundred seventy-eight brachytherapy and 9089 RP patients were included. Median age was 66 years (interquartile range [IQR] 61-71) and 63 years (IQR 58-67), respectively. Median follow-up time to event or censured was 14 years (IQR 11.5-17.3). The Kaplan-Meier estimates for pelvic second malignancy at 15 and 20 years were 6.4% and 9.8%, respectively, after brachytherapy, and 3.2% and 4.2% after RP. Time to any second malignancy and time to death from any second malignancy were not significantly different (P > .05). On Cox multivariable analysis, brachytherapy, compared to surgery, was an independent factor for pelvic (hazard ratio [HR] 1.81 [95% CI 1.45-2.26], P < .001) and invasive pelvic second malignancy (HR 2.13 [95% CI 1.61-2.83], P < .001). Increased age and smoking were also associated with higher estimates of events (P < .001). CONCLUSIONS: After adjustment for age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking status, numerically higher long-term HRs of pelvic and invasive pelvic second malignancy in patients treated with brachytherapy compared to RP were noted.

Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients.

BACKGROUND: Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS: Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS: A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS: This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

PURPOSE: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). METHODS: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. RESULTS: 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55 months [32.8-107.2] vs. 20 months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20 mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9 years (95% CI 3.3-not reached) for LC and a 3.8 years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5 years (95% CI 4.4-not reached) for LC and 6 years (95% CI 4.3-11.6) for RCCM + . CONCLUSIONS: Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.

Relative risk of second malignant neoplasms highest among young adult cancer patients - a population-based registry study in Finland.

BACKGROUND AND PURPOSE: The objective of this study was to explore the incidence of second malignant neoplasms (SMNs) among adult cancer patients in Finland diagnosed with their first primary cancer (FPC) in 1992-2021. MATERIAL AND METHODS: The study used data from the population-based Finnish Cancer Registry (FCR). Risk estimates were calculated using the standardised incidence ratio (SIR), the ratio of observed second cancers compared to the expected numbers assuming the same cancer incidence as the corresponding sex-age-calendar year -split of the general population. RESULTS: A total of 573,379 FPCs were diagnosed during 1992-2021. During the follow-up, 60,464 SMNs were diagnosed. Male cancer patients had neither a decreased nor an increased risk (SIR 1.00 [95% CI, 0.99-1.01]) and female patients had an 8% increased risk (SIR 1.08 [95% CI, 1.06-1.09]) of developing any SMN compared to a FPC in the general population. The highest SIR of any SMN was observed in patients aged 20-39 -years at FPC diagnosis, and the SIR decreased by increasing age at diagnosis. Patients with lymphoid and haematopoietic tissue neoplasms, cancers of the mouth and pharynx, endocrine glands, respiratory and intrathoracic organs, skin, and urinary organs had the highest SIRs, while patients with cancers of the male genital organs and the female breast had the lowest SIRs. INTERPRETATION: Elevated SIRs were observed in cancer patients diagnosed at an early age and for FPCs known to be in large part attributable to lifestyle factors, which highlights the importance of monitoring and encouraging lifestyle changes.

The impact of baseline health factors on second primary cancer risk after radiotherapy for prostate cancer.

PURPOSE: In evaluating second primary cancers (SPCs) following External Beam Radiotherapy (EBRT), the role of lifestyle factors is frequently not considered due to data limitations. We investigated the association between smoking, comorbidities, and SPC risks within EBRT-treated patients for localized prostate cancer (PCa). PATIENTS & METHODS: The study included 1,883 PCa survivors aged 50-79, treated between 2006 and 2013, with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT). Clinical data were combined with SPC and survival data from the Netherlands Cancer Registry with a 12-month latency period. Standardized Incidence Ratios (SIRs) were calculated comparing the EBRT cohort with the general Dutch population. To explore the effect of patient and treatment characteristics on SPCs we conducted a Cox regression analysis. Lastly, we estimated cumulative incidences of developing solid SPC, pelvis SPC, and non-pelvis SPC using a competing risk analysis. RESULTS: Significantly increased SIRs were observed for all SPC (SIR = 1.21, 95% confidence interval [CI]: 1.08-1.34), pelvis SPC (SIR = 1.46, 95% CI: 1.18-1.78), and non-pelvis SPC (SIR = 1.18, 95% CI [1.04-1.34]). Smoking status was significantly associated with pelvic and non-pelvic SPCs. Charlson comorbidity index (CCI) ≥ 1 (Hazard Ratio [HR] = 1.45, 95% CI: 1.10-1.91), cardiovascular disease (HR = 1.41, 95% CI: 1.05-1.88), and chronic obstructive pulmonary disease (COPD) (HR = 1.91, 95% CI: 1.30-2.79) were significantly associated with non-pelvis SPC. The proportion of active smoking numbers in the cohort was similar to the general population. INTERPRETATION: We conclude that the presence of comorbidities in the EBRT population might be a relevant factor in observed excess non-pelvis SPC risk, but not for excess pelvis SPC risk.

Gastrointestinal: Weight gain increases the risk of metachronous advanced colorectal neoplasm observed in post-polypectomy surveillance colonoscopy.

BACKGROUND AND AIM: Although obesity is a known risk factor for colorectal neoplasms, the correlation between weight change and colorectal neoplasm is unclear. Thus, we aim to evaluate the association between weight change and advanced colorectal neoplasm (ACRN) recurrence during post-polypectomy surveillance colonoscopy. METHODS: This retrospective cohort study included 7473 participants diagnosed with colorectal neoplasms between 2003 and 2010 who subsequently underwent surveillance colonoscopies until 2020. We analyzed the association between the risk of metachronous ACRN and weight change, defining stable weight as a weight change of <3% and weight gain as a weight increase of ≥3% from baseline during the follow-up period. RESULTS: During a median 8.5 years of follow-up, 619 participants (8.3%) developed ACRN. Weight gain was reported as an independent risk factor for metachronous ACRN in a time-dependent Cox analysis. A weight gain of 3-6% and ≥6% had adjusted hazard ratios (AHRs) of 1.48 (95% confidence interval [CI]: 1.19-1.84) and 2.14 (95% CI: 1.71-2.69), respectively. Participants aged 30-49 and 50-75 years with weight gain of ≥6% showed AHRs of 2.88 (95% CI: 1.96-4.21) and 1.90 (95% CI: 1.43-2.51), respectively. In men and women, weight gain of ≥3% was significantly correlated with metachronous ACRN. CONCLUSIONS: Weight gain is associated with an increased risk of metachronous ACRN. Furthermore, weight gain is associated with the recurrence of ACRN in both men and women regardless of age.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Second Malignant Neoplasms Following Treatment for Hepatoblastoma: An International Report and Review of the Literature.

Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects, including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Thirty-eight patients were identified. The median age at diagnosis of HB was 16 months (range: 3 to 168 mo). All patients had received a platinum agent, and almost all had anthracycline exposure. The SMNs reported were hematopoietic malignancies (n=19), solid tumors (n=12), and post-transplant lymphoproliferative disorder (n=7). Of the 36 patients with outcome data, 19 survived. SMNs following HB treatment were primarily seen in patients with chemotherapy exposure, a history of liver transplantation, hereditary tumor predisposition syndromes, and/or a history of radiation treatment. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data through a companion late effects study or international registry could be used to further evaluate the rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB.

Risk for second primary cancers among pediatric and young adult melanoma survivors.

BACKGROUND/OBJECTIVES: Second primary cancers (SPCs) are a leading cause of morbidity and mortality among cancer survivors. In this study, we aimed to characterize the incidence of SPCs among pediatric and young adult survivors of CM. METHODS: Using the Surveillance, Epidemiology, and End Results Program data spanning 2000-2018, we calculated standardized incidence ratios (SIR) to assess SPC risk in all pediatric (0-18 years) and young adult (19-29 years) patients with a first primary cancer diagnosis of CM. RESULTS: Of 7,169 total CM survivors, 632 (8.82%) developed a SPC, corresponding to a 5-fold increased risk (standardized incidence ratio [SIR] 4.98; 95% confidence interval [CI] 4.60-5.38) compared to the general population. There was a highly elevated risk for second primary melanoma across all age groups (SIR 32.5; 95% CI 29.7-35.6), constituting the majority of SPC diagnoses (N = 485). Infants diagnosed with CM before 1 year of age had the highest risk for any SPC (SIR 164; 95% CI 19.8-592) and young adults diagnosed at 25-29 years had the lowest risk (SIR 4.64; 95% CI 4.19-5.13). SPC incidence was highest within the first year of CM diagnosis (SIR 27.5; 95% CI 23.7-31.6) and progressively decreased with time. CONCLUSIONS: Variation exists in the incidence and type of SPC according to age among pediatric and young adult survivors of CM.