Excess Absolute Risk Research Articles

The influence of daily imaging and target margin reduction on secondary cancer risk in image-guided and adaptive proton therapy

Objective. Image-guided and adaptive proton therapy rely on daily CBCT or CT imaging, which increases radiation dose and radiation-induced cancer risk. Online adaptation however also reduces setup uncertainty, and the additional risk might be compensated by reducing the setup robustness margin. This work developed a framework to investigate how much this robustness margin should be reduced to offset the secondary cancer risk from additional imaging dose and applied it to proton therapy for head-and-neck cancer.Approach. For five patients with head-and-neck cancer, voxel-wise CT and CBCT imaging doses were estimated with Monte Carlo radiation transport simulations, calibrated with air and PMMA phantom measurements. The total dose of several image-guided and adaptive treatments protocols was calculated by summing the planning CT dose, daily and weekly CBCT or CT dose, and therapy dose, robustly optimized with setup margins between 0 and 4 mm. These were compared to a reference protocol with 4 mm setup margin without daily imaging. All plans further used 3% range robustness. Organ-wise excess absolute risk (EAR) of cancer was calculated with three models to determine at which setup margin the total EAR of image-guided and adaptive treatment protocols was equal to the total EAR of the reference.Results. The difference between the simulated and measured CT and CBCT doses was within 10%. Using the Monte Carlo models, we found that a 1 mm setup margin reduction was sufficient for most patients, treatment protocols, and cancer risk models to compensate the additional risk imposed by daily and weekly imaging. For some protocols, even a smaller reduction sufficed, depending on the imaging frequency and type. The risk reduction by reducing the margin was mainly due to reducing the risk for carcinomas in the brain and, for some patients, the oral cavity.Significance. Our framework allows to compare an increased imaging dose with the reduced treatment dose from margin reductions in terms of radiation-induced cancer risk. It is extendable to different treatment sites, modalities, and imaging protocols, in clinic-specific or even patient-specific assessments.

A note on potential gains in precision of radiation risk estimates from joint analysis.

In estimating radiation-related risk of cancer and other diseases based on the RERF Life Span Study (LSS), joint analyses can be performed where multiple health outcome endpoints are combined in the same model, allowing some parameters to be estimated in common among all endpoints with possible increase in precision of radiation risk and other model parameter estimates. Using as a basis excess relative risk (ERR) and excess absolute risk (EAR) models of the type commonly used in analysis of LSS data at RERF, we use maximum likelihood theory to compute the asymptotic relative standard error of endpoint-specific radiation effect and other parameter estimates using joint analyses as compared to traditional independent analysis. We show that some gains in precision of endpoint-specific radiation risk parameter estimates can be achieved by sharing effect modifier and other model parameters, but only small or negligible gains in precision are achieved for endpoint-specific background modifying or effect modifying parameters when other model parameters are shared. The magnitude of the precision gain for radiation risk estimates depends on the number of endpoints, the baseline incidence rate of the endpoint, and the type of model being used.

Risk of second primary cancers in nodal non-Hodgkin lymphoma patients by primary lymph node location: a retrospective cohort population-based study.

Non-Hodgkin lymphoma (NHL) is a diverse group of blood cancers with increasing incidence and survival rates due to advancements in treatment and early detection. However, NHL survivors are at significant risk of developing second primary cancers, which can adversely impact their long-term survival. This retrospective population-based cohort study utilized data from the Surveillance, Epidemiology, and End Results database, covering 17 geographic areas in the United States from 2000 to 2021. The authors included patients diagnosed with nodal NHL as a first primary cancer and excluded those diagnosed at autopsy or via death certificate only. Standardized Incidence Ratios, Absolute Excess Risks, and Person-Years at Risk were calculated to evaluate the risk of developing SPCs according to the primary lymph node site and stratified by latency periods following the initial NHL diagnosis. The cohort included 54012 NHL patients. The authors' results showed that for most SPCs, the risk of development was different for different primary NHL lymph node locations. The highest risks were observed for thyroid cancer, acute myeloid leukemia, and Hodgkin lymphoma. Notably, the risk for thyroid cancer was highest in the first year post-diagnosis, while hematological malignancies such as acute myeloid leukemia and Hodgkin lymphoma showed elevated risks in the intermediate and late latency periods. NHL survivors are at an increased risk of developing SPCs, influenced by the primary lymph node site and latency period. These findings highlight the need for tailored surveillance strategies and preventive measures to mitigate the long-term risks of SPCs in NHL survivors. Further research is necessary to elucidate the underlying mechanisms and to develop targeted interventions for this high-risk population.

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Long-Term Risk of Subsequent Neoplasms in 5-Year Survivors of Childhood Neuroblastoma: A Dutch Childhood Cancer Survivor Study-LATER 3 Study.

Neuroblastoma survivors have an increased risk of developing subsequent malignant neoplasms (SMNs), but the risk of subsequent nonmalignant neoplasms (SNMNs) and risk factors are largely unknown. We analyzed the long-term risks and associated risk factors for developing SMNs and SNMNs in a well-characterized cohort of 5-year neuroblastoma survivors. We included 563 5-year neuroblastoma survivors from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort, diagnosed during 1963-2014. Subsequent neoplasms were ascertained by linkages with the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (Palga) and medical chart review. We calculated standardized incidence ratios (SIRs), absolute excess risk (AER), and cumulative incidences. Multivariable competing risk regression analysis was used to evaluate risk factors. In total, 23 survivors developed an SMN and 60 an SNMN. After a median follow-up of 23.7 (range, 5.0-56.3) years, the risk of SMN was elevated compared with the general population (SIR, 4.0; 95% CI, 2.5 to 5.9; AER per 10,000 person-years, 15.1). The 30-year cumulative incidence was 3.4% (95% CI, 1.9 to 6.0) for SMNs and 10.4% (95% CI, 7.3 to 14.8) for SNMNs. Six survivors developed an SMN after iodine-metaiodobenzylguanidine (131IMIBG) treatment. Survivors treated with 131IMIBG had a higher risk of developing SMNs (subdistribution hazard ratio [SHR], 5.7; 95% CI, 1.8 to 17.8) and SNMNs (SHR, 2.6; 95% CI, 1.2 to 5.6) compared with survivors treated without 131IMIBG; results for SMNs were attenuated in high-risk patients only (SMNs SHR, 3.6; 95% CI, 0.9 to 15.3; SNMNs SHR, 1.5; 95% CI, 0.7 to 3.6). Our results demonstrate that neuroblastoma survivors have an elevated risk of developing SMNs and a high risk of SNMNs. 131IMIBG may be a treatment-related risk factor for the development of SMN and SNMN, which needs further validation. Our results emphasize the need for awareness of subsequent neoplasms and the importance of follow-up care.

Cardiovascular death risk in patients with solid tumors: a population-based study in the United States.

Previous studies have focused on the risk of cardiovascular disease (CVD)-specific death in hematological cancers and in some single anatomical tumor sites, there remains a paucity of data on systematic analyses in solid tumors. The objective of this study is to evaluate the distribution, risk, and trends of CVD-specific death in patients with solid tumors. A total of 2 679 293 patients with solid tumors diagnosed between 1975 and 2019 were screened from the Surveillance, Epidemiology and End Results (SEER) program across 15 anatomical sites. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to describe the intensity of CVD-specific death, competing risk regression models were used to assess the risk of CVD-specific death, and restricted cubic spline analyses were employed to investigate the potential linear or nonlinear relationship between age and CVD death. CVD-specific death in patients with solid tumors accounted for 48.95% of non-cancer deaths. Compared with the general population, patients with solid tumors had higher SMR and AER of CVD death (SMR: 1.15; AER: 21.12), heart disease-related death (SMR: 1.13; AER: 13.96), and cerebrovascular disease-related death (SMR: 1.20; AER: 4.85). Additionally, the SMR exhibited a decreasing trend with increasing time to diagnosis. Furthermore, a nonlinear relationship was observed between age and CVD-specific death in patients with solid tumors of different systems. CVD-specific death accounted for a large proportion of the cause of non-cancer deaths. Patients with solid tumors exhibit an elevated risk of CVD-specific death. Screening for CVD death and optimizing risk management in patients with solid tumors throughout anticancer treatment may be beneficial in preventing CVD death.

Overall survival and cause-specific mortality in a hospital-based cohort of retinoblastoma patients in São Paulo, Brazil.

Studies are lacking on long-term effects among retinoblastoma patients in low- and middle-income countries. Therefore, we examined cause-specific mortality in a retrospective cohort of retinoblastoma patients treated at Antonio Candido de Camargo Cancer Center (ACCCC), São Paulo, Brazil from 1986 to 2003 and followed up through December 31, 2018. Vital status and cause of death were ascertained from medical records and multiple national databases. We estimated overall and cause-specific survival using the Kaplan-Meier survival method, and estimated standardized mortality ratios (SMRs) and absolute excess risk (AER) of death. This cohort study included 465 retinoblastoma patients (42% hereditary, 58% nonhereditary), with most (77%) patients diagnosed at advanced stages (IV or V). Over an 11-year average follow-up, 80 deaths occurred: 70% due to retinoblastoma, 22% due to subsequent malignant neoplasms (SMNs) and 5% to non-cancer causes. The overall 5-year survival rate was 88% consistent across hereditary and nonhereditary patients (p = .67). Hereditary retinoblastoma patients faced an 86-fold higher risk of SMN-related death compared to the general population (N = 16, SMR = 86.1, 95% CI 52.7-140.5), corresponding to 42.4 excess deaths per 10,000 person-years. This risk remained consistent for those treated with radiotherapy and chemotherapy (N = 10, SMR = 90.3, 95% CI 48.6-167.8) and chemotherapy alone (N = 6, SMR = 80.0, 95% CI 35.9-177.9). Nonhereditary patients had only two SMN-related deaths (SMR = 7.2, 95% CI 1.8-28.7). There was no excess risk of non-cancer-related deaths in either retinoblastoma form. Findings from this cohort with a high proportion of advanced-stage patients and extensive chemotherapy use may help guide policy and healthcare planning, emphasizing the need to enhance early diagnosis and treatment access in less developed countries.

A mini review of plan quality and secondary cancer risk in CyberKnife M6 radiosurgery for benign intracranial tumors.

With advancements in medical technology, stereotactic radiosurgery (SRS) has become an essential option for treating benign intracranial tumors. Due to its minimal side effects and high local control rate, SRS is widely applied. This paper evaluates the plan quality and secondary cancer risk (SCR) in patients with benign intracranial tumors treated with the CyberKnife M6 system. The CyberKnife M6 robotic radiosurgery system features both multileaf collimator (MLC) and IRIS variable aperture collimator systems, providing different treatment options. The study included 15 patients treated with the CyberKnife M6 system, examining the differences in plan quality and SCR between MLC and IRIS systems. Results showed that MLC and IRIS plans had equal PTV (planning target volume) coverage (98.57% vs. 98.75%). However, MLC plans demonstrated better dose falloff and conformity index (CI: 1.81 ± 0.26 vs. 1.92 ± 0.27, P = 0.025). SCR assessment indicated that MLC plans had lower cancer risk estimates, with IRIS plans having average LAR (lifetime attributable risk) and EAR (excess absolute risk) values approximately 25% higher for cancer induction and 15% higher for sarcoma induction compared to MLC plans. The study showed that increasing tumor volume increases SCR probability, but there was no significant difference between different plans in PTV and brainstem analyses.

Underlying disease risk among fatigued patients: a population-based cohort study in primary care.

Background Presenting to primary care with fatigue is associated with a wide range of conditions, including cancer, although their relative likelihood is unknown. Aim To quantify associations between new-onset fatigue presentation and subsequent diagnosis of various diseases, including cancer. Design and setting Cohort study of patients presenting in English primary care with new-onset fatigue during 2007-2017 (fatigue presenters (FPs)), compared to non-fatigue presenters (NFPs), using Clinical Practice Research Datalink data linked to hospital episodes and national cancer registration data. Method We described excess short-term incidence of 237 diseases in FPs compared to NFPs. We modelled disease-specific 12-month risk by sex and calculated age-adjusted risk. Results We included 304,914 FPs and 423,671 NFPs. 127 of 237 diseases studied were more common in male FPs than in male NFPs, and 151 were more common in female FPs. Diseases that were most strongly associated with fatigue included: depression; insomnia & sleep disturbances, and hypo/hyperthyroidism (women only). By 80 years, cancer was the 3rd most common disease and had the 4th highest absolute excess risk in male FPs (FPs: 7.0%, CI = 6.6 to 7.5; NFPs: 3.4%, CI = 3.1 to 3.7; AER: 3.7%). In women, cancer remained relatively infrequent; by age 80 it had the 13th highest excess risk in FPs. Conclusion Our study ranks the likelihood of possible diagnoses in fatigue presenters, to inform diagnostic guidelines and doctors' decisions. Age-specific findings support recommendations to prioritise cancer investigation in older men with fatigue, but not women.

Second primary malignancy for early-stage head and neck squamous cell carcinoma by SEER17 registries.

Investigating treatment modalities' association with second primary malignancy risk in early-stage head and neck squamous cell carcinoma (HNSCC). Data of 5-year survivors of early-stage (stages I-II, seventh TNM staging manual) HNSCC from 2000 to 2020 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio and excess absolute risk were used to assess second primary malignancy (SPM) development externally. Relative risk was estimated to compare SPM risk within groups. Fine-Gray's model estimated cumulative incidence of second primary malignancy. Overall, 8957 5-year survivors with early-stage HNSCC were enrolled. Patients receiving definitive radiotherapy had poorer survival than surgery patients. Surgery correlated with lower risk of second primary malignancy (RR = 0.89, 95% CI 0.80-0.99), especially for oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39-0.82). Differences in the risk of second primary malignancy among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect risk of second primary malignancy within each subgroup. Surgery led to better survival and lower risk of second primary malignancy compared to definitive radiotherapy in 5-year survivors. Incidence and sites of second primary malignancy varied by primary sites, emphasizing targeted long-term surveillance's importance.

Langerhans cell histiocytosis in children born after assisted reproductive technology

Research QuestionAre children born after Assisted reproductive technologies (ART), at higher risk of developing Langerhans cell histiocytosis (LCH)? DesignRecords of children conceived after ART recorded by the Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine numbers of children developing LCH. Calculated person years at risk were used in conjunction with LCH incidence in the general population, to determine expected cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardised incidence ratio (SIR) was derived as the ratio of observed to expected cases. Exact 95% confidence intervals were calculated. Results118,155 children born after ART contributed 796,633 person years follow-up; 6.74 years average follow-up. Eight cases of LCH were identified compared to 3.75 expected (SIR 2.135, 95% Confidence Interval 0.92 to 4.21, p = 0.074). Significantly more cases were associated with being born after intra-cytoplasmic sperm injection (SIR 4.02; 95% CI 1.31-9.39) and with male factor parental infertility (SIR 5.41; 95% CI 1.47-13.84). Most children had single system disease (n=6). ConclusionsThis study found a non-statistically significant excess of cases of LCH in children born after assisted reproduction. Significantly more cases were identified in children born after ICSI and after male factor parental infertility. Absolute excess risks were small. Given the rarity of LCH and small numbers of cases included in this large cohort, further studies into the risk of LCH in children born after ART are indicated.

Cancer incidence following bariatric surgery in renal transplant recipients: a retrospective multi-center analysis

BackgroundObesity, a known independent risk factor for developing malignancy. Additionally, renal transplant recipients (RTR) confer a 2- to 4-fold increased risk of overall malignancies with an excess absolute risk of .7% per year. While transplant recipients are at risk for obesity and malignancy, the effect of bariatric surgery (BS) in the posttransplantation setting is not well known. ObjectivesOur study primarily evaluated the impact of BS on cancer incidence in RTR with severe obesity in the posttransplantation setting. Weight loss outcomes were analyzed secondarily. SettingUniversity Hospital. MethodsA retrospective study using TriNetX database was developed to analyze cancer outcomes in RTR with posttransplantation BS versus RTR without BS from 2000 to 2023. After the exclusion process and propensity matching, both cohorts consisted of 153 patients. ResultsRTR-BS had a significantly lower incidence of overall cancer and transplant-related cancers (P < .05). No significant difference was identified in cutaneous, gastrointestinal, and reproductive cancers. Percent Excess Weight Loss (%EWL) was significantly lower in RTR-only cohort (11.4%) versus RTR-BS cohort (57.8%) at 5 years. Sleeve gastrectomy (SG) patients (73.19%) had significantly higher %EWL than Roux en-Y gastric bypass (RYGB) patients (49.33%) at 3 years. No difference in cancer incidence was noted between SG and RYGB patients. ConclusionPostrenal transplantation BS had a diminishing effect on overall and transplant-related cancer incidence in RTR with severe obesity. Significant weight loss was also demonstrated with post-renal transplantation BS.

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient’s position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). 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. 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. 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.

Cancer risks for other sites in addition to breast in CHEK2 c.1100delC families

PurposeFemale CHEK2 c.1100delC heterozygotes are eligible for additional breast surveillance because of an increased breast cancer risk. Increased risks for other cancers have been reported. We studied whether CHEK2 c.1100delC is associated with an increased risk for other cancers within these families. MethodsIncluding 10,780 individuals from 609 families, we calculated standardized incidence rates (SIRs) and absolute excess risk (AER, per 10,000 person-years) by comparing first-reported cancer derived from the pedigrees with general Dutch population rates from 1970 onward. Attained-age analyses were performed for sites in which significant increased risks were found. Considering the study design, we primarily focused on cancer risk in women. ResultsWe found significant increased risks of colorectal cancer (CRC; SIR = 1.43, 95% CI = 1.14-1.76; AER = 1.43) and hematological cancers (SIR = 1.32; 95% CI = 1.02-1.67; AER = 0.87). CRC was significantly more frequent from age 45 onward. ConclusionA significantly increased risk of CRC, and hematological cancers in women was found, starting at a younger age than expected. Currently, colorectal surveillance starts at age 45 in high-risk individuals. Our results suggest that some CHEK2 c.1100delC families might benefit from this surveillance as well; however, further research is needed to determine who may profit from this additional colorectal surveillance.

Helium Ion Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma.

Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications.

Long-Term Risks of Cardiovascular Death among Older Patients with Major Hematological Malignancies: A Population-Based Cohort Study from SEER Database.

The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM). This study included 103,102 older patients diagnosed with seven major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result database. The proportion of deaths, Fine-Gray subdistribution hazards regression model, standardized mortality ratios (SMR), and absolute excess risk (AER) were used to evaluate the risk of CVD-related death. For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular disease-related deaths (SMR: 0.99-1.66; AER: -0.35 to 24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in patients with Hodgkin lymphoma with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types. For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy. Our results emphasize the need to manage long-term cardiovascular risk in older patients with hematological malignancies, especially in those identified as high-risk cases.

Subsequent malignant neoplasms after primary hematological malignancy in adult patients.

Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person-years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7-5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4-1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20-39 years (SIR 9.2, 95% CI 6.8-12.2 in males and SIR 10.5, 95% CI 7.2-14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60-79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients.

Abstract LB151: Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States

Abstract Background Breast cancer survivors face an elevated risk of subsequent primary lung cancer (SPLC), especially those who received radiotherapy. Nevertheless, the association of radiotherapy for breast cancer and the risk of subtype-specific lung cancer is unknown. Methods Females diagnosed with first primary breast cancer at ages 20-84 years from 1992-2020 were identified from 12 Surveillance, Epidemiology, and End Results registries. Follow-up began at 2 months from breast cancer diagnosis and ended at subsequent lung cancer diagnosis, last known vital status, death, or December 31, 2020. Standardized incidence ratios (SIRs) and excess absolute risks (EARs, per 10,000 women) were calculated for each histological subtype of lung cancer (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell carcinoma, and others) using expected rates of each subtype in the SEER population. Subgroup analyses were conducted by treatment for breast cancer (radiotherapy yes or no/unknown), overall and stratified by the relative position (ipsilateral and contralateral) of the breast and SPLC. Results Of all 550,007 breast cancer survivors (&amp;gt;50 years old, 74%; non-Hispanic Whites, 67%; localized, 51%), 8,014 SPLCs were diagnosed during a mean follow-up of 9.7 years. 52.6% of the participants received radiotherapy treatment. Compared with the general population, breast cancer survivors had a statistically significantly higher risk of lung cancer with subtype-specific SIR being greatest for adenocarcinoma (Observed N=4337; SIR=1.20, 95% Confidence Interval [CI]=1.16-1.24; EAR=1.35), followed by squamous cell carcinoma (Observed N=1368; SIR=1.11, 95% CI=1.05-1.17; EAR=0.26) and small cell carcinoma (Observed N=1026; SIR=1.08, 95% CI=1.02-1.15; EAR=0.14). When stratified by radiotherapy receipt, the increased risk associated with adenocarcinoma did not vary across strata. In contrast, the increased risk for squamous and transitional cell carcinoma and small cell carcinoma were confined to those who received radiotherapy (SIR=1.16, 95% CI=1.08-1.24 vs SIR=1.06, 95% CI=0.98-1.15 for squamous and transitional cell carcinoma; SIR=1.15, 95% CI=1.06-1.25 vs SIR= 1.00, 95% CI=0.91-1.09 for small cell carcinoma). Further analysis by laterality showed that associations of treatment receipt with increased risk of lung cancer were confined to ipsilateral SPLC for these two subtypes. Conclusion Different subtypes of lung cancer may have distinct associations with prior radiation treatment in individuals who have survived breast cancer. The findings have implications for evaluating risks and implementing surveillance for subsequent primary lung cancer in the growing population of breast cancer survivors. Citation Format: Chenxi Jiang, Rachel A. Freedman, Ahmedin Jemal, Hyuna Sung. Association of radiotherapy with the risk of subtype-specific lung cancer among breast cancer survivors in the United States [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB151.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials.

Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes randomized to PCI versus CABG. Individual patient data were pooled from 4 trials (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], NOBLE [Nordic-Baltic-British Left Main Revascularisation Study], and EXCEL [Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization]) that randomized patients with left main disease to PCI or CABG. Patients were considered suitable for either approach. Patients were categorized by diabetes status. Kaplan-Meier event rates, Cox model hazard ratios, and interactions were assessed. Among 4393 patients, 1104 (25.1%) had diabetes. Patients with diabetes experienced higher rates of 5-year death (158/1104 [Kaplan-Meier rate, 14.7%] versus 297/3289 [9.3%]; P<0.001), spontaneous myocardial infarction (MI; 67/1104 [6.7%] versus 114/3289 [3.7%]; P<0.001), and repeat revascularization (189/1104 [18.5%] versus 410/3289 [13.2%]; P<0.001). Rates of all-cause mortality did not differ after PCI versus CABG in those with (84/563 [15.3%] versus 74/541 [14.1%]; hazard ratio, 1.11 [95% CI, 0.82-1.52]) or without (155/1634 [9.7%] versus 142/1655 [8.9%]; hazard ratio, 1.08 [95% CI, 0.86-1.36; PintHR=0.87) diabetes. Rates of stroke within 1 year were lower with PCI versus CABG in the entire population, with no heterogeneity based on diabetes status (PintHR=0.51). The 5-year rates of spontaneous MI and repeat coronary revascularization were higher after PCI regardless of diabetes status (spontaneous MI: 45/563 [8.9%] versus 22/541 [4.4%] in diabetes and 82/1634 [5.3%] versus 32/1655 [2.1%] in no diabetes, PintHR=0.47; repeat revascularization: 127/563 [24.5%] versus 62/541 [12.4%] in diabetes and 254/1634 [16.3%] versus 156/1655 [10.1%] in no diabetes, PintHR=0.18). For spontaneous MI and repeat revascularization, there were greater absolute risk differences beyond 1 year in patients with diabetes (4.9% and 9.9%) compared with those without (2.1% and 4.3%; PintARD=0.047 and 0.016). In patients with left main disease considered equally suitable for PCI or CABG and with largely low to intermediate SYNTAX scores, diabetes was associated with higher rates of death and cardiovascular events through 5 years. Compared with CABG, PCI resulted in no difference in the risk of death and a lower risk of early stroke regardless of diabetes status, and a higher risk of spontaneous MI and repeat coronary revascularization, with larger late absolute excess risks in patients with diabetes. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01205776, NCT0146651, NCT00422968, and NCT00114972.