Impact of Advanced Radiotherapy on Second Primary Cancer Risk in Prostate Cancer Survivors: A Nationwide Cohort Study.
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ABSTRACT:
SUBMITTER: Jahreiß MC
PROVIDER: S-EPMC8662556 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000-2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy's impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06-1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.
| S-EPMC11291913 | biostudies-literature
Project description:PurposeConcerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors.Material and methodsThe study cohort comprised 1,561 PCa survivors aged 50-79 years at time of radiotherapy, treated between 2006-2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age.ResultsMedian follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (p=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03-2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, p=0.01). Within the age subgroups 50-69 and 70-79 years, the sHR for non-pelvic SPC was 3.27 (p=0.001) and 0.96 (p=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, p=0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50-69 year age group (SIR=1.90, p<0.05) but not in the 70-79 years group (SIR=1.08).ConclusionIMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.
| S-EPMC7691574 | biostudies-literature
Project description:To assess etiological and clinical consequences of second primary cancers (SPCs) in prostate cancer (PC) patients, we followed newly diagnosed patients to identify men who were diagnosed with a SPC and recorded their causes of death. We used the Swedish Family-Cancer Database to assess relative risks (RRs) and causes of death in SPCs until the year 2015 in patients with a PC diagnosis between 2001 and 2010. Among a total of 4.26 million men, 76 614 were diagnosed with PC at the median age of 71 years. Among them, 8659 (11.3%) received a subsequent diagnosis of SPC after a median follow-up of 4 years. The most common SPCs were colorectal, skin, bladder, and lung cancers, melanoma, and non-Hodgkin lymphoma. The ranking was almost identical with first cancers among elderly men in Sweden. The RR for SPCs in prostate-specific antigen-detected PC was approximately equal to RR in other PC. Mortality patterns of PC patients were distinct depending on the presence or absence of SPC. Among patients with SPC, 47.8% died as a result of the corresponding SPC, followed by other causes (22.2%) and PC (18.1%). For patients without SPC, PC and non-neoplastic causes almost matched each other as the main causes of death (48.5% and 47.8%). The results suggest that SPCs appear autonomous from primary PC and reflect incidence and mortality of first cancers in general. SPC was the most common cause of death in patients with SPC; close to half of the patients died due to SPC. For improved survival in PC patients, prevention and early detection of SPCs would be important, and the present results suggest that risk factors for SPC in PC are the same as those for first cancer in general.
| S-EPMC6246949 | biostudies-literature
Project description:Limited information exists about survival outcomes after second primary cancers (SPCs) among breast cancer survivors. Studies suggest that mortality after certain SPCs may be higher than mortality after first primary cancers (FPCs) of the same type. A cohort study was conducted among 63,424 US women using the Surveillance, Epidemiology, and End Results 18 database (2000-2016) to compare mortality after a SPC among breast cancer survivors to mortality among women after a FPC using Cox proportional hazard regression. Propensity scores were used to match survivors with SPCs to women with FPCs 1:1 based on cancer type and prognostic factors. During a median follow-up of 42 months, 11,532 cancer deaths occurred after SPCs among survivors compared to 9305 deaths after FPCs. Cumulative cancer mortality was 44.7% for survivors with SPCs and 35.2% for women with FPCs. Survivors with SPCs had higher risk of cancer death (hazard ratio (HR): 1.27, 95% CI: 1.23-1.30) and death overall (HR: 1.18, 95% CI: 1.15-1.21) than women with FPCs. Increased risk of cancer death after SPCs compared to FPCs was observed for cancer in breast, lung, colon and/or rectum, uterus, lymphoma, melanoma, thyroid, and leukemia. Estrogen receptor status and treatment of the prior breast cancer as well as time between prior breast cancer and SPC significantly modified the mortality difference between women with SPC and FPC. A more tailored approach to early detection and treatment could improve outcomes from second cancer in breast cancer survivors.
| S-EPMC9283416 | biostudies-literature
Project description:ImportanceShared decision-making is an important part of the treatment selection process among patients with prostate cancer. Updated information is needed regarding the long-term incidence and risk of second primary cancer after radiotherapy vs nonradiotherapy treatments, which may help to inform discussions of risks and benefits for men diagnosed with prostate cancer.ObjectiveTo assess the current incidence and risk of developing a second primary cancer after receipt of radiotherapy vs nonradiotherapy treatments for prostate cancer.Design, setting, and participantsThis retrospective cohort study used the Veterans Affairs Corporate Data Warehouse to identify 154 514 male veterans 18 years and older who had localized prostate cancer (tumor stages T1-T3) diagnosed between January 1, 2000, and December 31, 2015, and no cancer history. A total of 10 628 patients were excluded because of (1) incomplete treatment information for the year after diagnosis, (2) receipt of both radiotherapy and a surgical procedure in the year after diagnosis, (3) receipt of radiotherapy more than 1 year after diagnosis, (4) occurrence of second primary cancer or death within 1 year or less after diagnosis, (5) prostate-specific antigen value greater than 99 ng/mL within 6 months before diagnosis, or (6) no recorded Veterans Health Administration service after diagnosis. The remaining 143 886 patients included in the study had a median (IQR) follow-up of 9 (6-13) years. Data were analyzed from May 1, 2021, to May 22, 2022.Main outcomes and measuresDiagnosis of a second primary cancer more than 1 year after prostate cancer diagnosis.ResultsAmong 143 886 male veterans (median [IQR] age, 65 [60-71] years) with localized prostate cancer, 750 (0.5%) were American Indian or Alaska Native, 389 (0.3%) were Asian, 37 796 (26.3%) were Black or African American, 933 (0.6%) were Native Hawaiian or other Pacific Islander, 91 091 (63.3%) were White, and 12 927 (9.0%) were of unknown race; 7299 patients (5.1%) were Hispanic or Latino, 128 796 (89.5%) were not Hispanic or Latino, and 7791 (5.4%) were of unknown ethnicity. A total of 52 886 patients (36.8%) received primary radiotherapy, and 91 000 (63.2%) did not. A second primary cancer more than 1 year after prostate cancer diagnosis was present in 4257 patients (3.0%), comprising 1955 patients (3.7%) in the radiotherapy cohort and 2302 patients (2.5%) in the nonradiotherapy cohort. In the multivariable analyses, patients in the radiotherapy cohort had a higher risk of second primary cancer compared with those in the nonradiotherapy cohort at years 1 to 5 after diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.13-1.37; P < .001), with higher adjusted HRs in the subsequent 15 years (years 5-10: 1.50 [95% CI, 1.36-1.65; P < .001]; years 10-15: 1.59 [95% CI, 1.37-1.84; P < .001]; years 15-20: 1.47 [95% CI, 1.08-2.01; P = .02).Conclusions and relevanceIn this cohort study, patients with prostate cancer who received radiotherapy were more likely to develop a second primary cancer than patients who did not receive radiotherapy, with increased risk over time. Although the incidence and risk of developing a second primary cancer were low, it is important to discuss the risk with patients during shared decision-making about prostate cancer treatment options.
| S-EPMC9335142 | biostudies-literature
Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low ?/? ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.
| S-EPMC6069023 | biostudies-literature
Project description:BackgroundWith the increasing number of breast cancer (BC) diagnosed as a second primary malignancy after a first primary non-breast cancer (BCa-2), it is unclear about the familial risk of BC among women with a first-degree relative (FDR, parents or siblings) affected by a BCa-2.MethodsIn this Swedish nationwide cohort study, 5315 women with a FDR affected by BCa-2 and 115,048 women with a FDR affected by BC as the first primary cancer (BCa-1) were followed for the first primary invasive BC diagnosis. Relative risk (RR) of BC was estimated through Poisson regression by using 2,743,777 women without a family history of cancer as reference. The risk was stratified by the diagnostic age of BC in FDR, proband type, the time interval between the first primary cancer and BCa-2 in FDR as well as the site of first primary cancer diagnosed in FDR before BCa-2. We also calculated the cumulative incidence of BC from birth to a specific age for the three groups.ResultsThe cumulative incidence from birth to age 70 was 10% among women with a family history of BCa-2. The RR of BC with a family history of BCa-2 (RR, 1.68, 95%CI, 1.49 to 1.88) was comparable to that with BCa-1 (1.68, 1.63 to 1.73). The risk was largely consistent irrespective of proband type. The age of onset of BCa-2 in FDR (RR early-onset, 1.72 vs. RR late-onset 1.67) had less influence on the risk compared to BCa-1 in FDR (1.89 vs. 1.63). In the analysis stratified by the time between the first primary cancer and BCa-2 in relatives, the risks were largely similar. For the site of first primary cancer diagnosed in FDR before BCa-2, the increased BC risk was found in women whose FDRs were diagnosed with first primary gastric, colorectal, endometrial, ovarian, nervous system and endocrine gland cancers, and non-Hodgkin lymphoma.ConclusionsWomen with a family history of BCa-2 have a similar overall BC risk as those with a family history of BCa-1. The risk varied according to the site of first primary cancer diagnosed in FDR before BCa-2.
| S-EPMC8590230 | biostudies-literature
Project description:PurposeThe rising incidence and life expectancy associated with prostate cancer (PCa) has led to increasing interest in predicting the risk of second primary malignancies (SPMs) among PCa survivors, although data regarding SPMs after PCa are controversial.MethodsWe identified 30,964 patients from the National Health Insurance Research Database in Taiwan who had newly diagnosed PCa between 2000 and 2010. Each patient was randomly frequency-matched with an individual without PCa, based on age, comorbidity, and index year. Competing-risks regression models were used to estimate subhazard ratios (SHRs) of SPMs development associated with PCa. The Bonferroni adjustment was used in multiple comparisons.ResultsMen with PCa had a trend of lower risk of developing overall SPMs compared to those without PCa (adjusted SHR = 0.94, 99.72% confidence interval [CI] = 0.89-1.00, p = 0.06). The risks of lung and liver cancer were significantly lower. In contrast, these patients had a significantly higher risk of thyroid cancer. There is a trend for a higher risk of developing SPMs in the urinary bladder and rectum/anus. Further analyses indicated that PCa patients who received radiation therapy (RT) had an increased risk of overall SPMs, hematologic malignancies, esophageal cancer, liver cancer, lung cancer, and urinary bladder cancer compared with those who did not receive RT.ConclusionMen with PCa tended to have a lower risk of SPMs, but a significantly higher risk of subsequent thyroid cancer. Continued cancer surveillance is required among PCa survivors, especially in specific sites and in individuals who received RT.
| S-EPMC5383246 | biostudies-literature
Project description:OBJECTIVES:To compare the loss of working time due to sick leave by treatment strategy for localised prostate cancer. DESIGN:Nationwide cohort study. SETTING:Sweden. PARTICIPANTS:A total of 15?902 working-aged men with localised low or intermediate-risk prostate cancer diagnosed during 2007-2016 from the Prostate Cancer Data Base Sweden, together with 63?464 prostate cancer-free men. Men were followed until 2016. PRIMARY AND SECONDARY OUTCOME MEASURES:Using multistate Markov models, we calculated the proportion of men on work, sick leave, disability pension and death, together with the amount of time spent in each state. All-cause and cause-specific estimates were calculated. RESULTS:During the first 5?years after diagnosis, men with active surveillance as their primary treatment strategy spent a mean of 17 days (95%?CI 15 to 19) on prostate cancer-specific sick leave, as compared with 46 days (95%?CI 44 to 48) after radical prostatectomy and 44 days (95%?CI 38 to 50) after radiotherapy. The pattern was similar after adjustment for cancer and sociodemographic characteristics. There were no differences between the treatment strategies in terms of days spent on sick leave due to depression, anxiety or stress. Five years after diagnosis, over 90% of men in all treatment strategies were free from sick leave, disability pension receipt and death from any cause. CONCLUSIONS:Men on active surveillance experienced less impact on working life compared with men who received radical prostatectomy or radiotherapy. From a long-term perspective, there were no major differences between treatment strategies. Our findings can inform men diagnosed with localised prostate cancer on how different treatment strategies may affect their working lives.
| S-EPMC7064067 | biostudies-literature
Project description:The survival of men diagnosed with prostate cancer has improved over time, and the current 10-year relative survival rate is 99.7%. The long survival of patients with this common cancer raises questions about the risk of a second primary cancer and the need for continued surveillance.A population-based cohort of 441,504 men who were diagnosed with prostate cancer between 1992 and 2010 was identified from Surveillance, Epidemiology and End Results Program (SEER) data (SEER13). The standardized incidence ratio (SIR) was calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population.Prostate cancer survivors had a lower risk of being diagnosed with another cancer overall compared with the US population (SIR?=?0.60; 95% confidence interval, 0.60-0.61). The risks of leukemia and cancers of the oral cavity and pharynx, esophagus, stomach, colon and rectum, liver, gallbladder, pancreas, lung and bronchus, and larynx were significantly lower. Conversely, these patients had a greater risk of bladder, kidney, and endocrine and soft tissue cancers. Men who received treatment with radiation therapy (external-beam radiation therapy) had long-term increases in their risk of bladder cancer (SIR?=?1.42) and rectal cancer (SIR?=?1.70) risk compared with who did not receive radiation (SIRbladder ?=?0.76; SIRrectal ?=?0.74). There were significant racial differences in the risk of being diagnosed with a second primary cancer, and the magnitude and direction of these risks depended on tumor type.Prostate cancer survivors remain at risk of subsequent malignancies, and race and treatment choice important determinants of long-term risk.
| S-EPMC4195444 | biostudies-literature