Dataset Information

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

ABSTRACT:

Purpose

Concerns 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 methods

The 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.

Results

Median 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).

Conclusion

IMRT 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.

SUBMITTER: Jahreiß MC

PROVIDER: S-EPMC7691574 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

Jahreiß Marie-Christina MC Aben Katja K H KKH Hoogeman Mischa S MS Dirkx Maarten L P MLP de Vries Kim C KC Incrocci Luca L Heemsbergen Wilma D WD

Frontiers in oncology 20201113

<h4>Purpose</h4>Concerns 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.<h4>Material and methods</h4>The ...[more]

PMID: 33282746

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Project description:PurposeExternal Beam Radiotherapy (EBRT) techniques dramatically changed over the years. This may have affected the risk of radiation-induced second primary cancers (SPC), due to increased irradiated low dose volumes and scatter radiation. We investigated whether patterns of SPC after EBRT have changed over the years in prostate cancer (PCa) survivors.Materials and methodsPCa survivors diagnosed between 1990-2014 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were divided in three time periods, representing 2-dimensional Radiotherapy (RT), 3-dimensional conformal RT (3D-CRT), and the advanced RT (AdvRT) era. Standardized incidence ratios (SIR) and absolute excess risks (AER) were calculated to estimate relative and excess absolute SPC risks. Sub-hazard ratios (sHRs) were calculated to compare SPC rates between the EBRT and prostatectomy cohort. SPCs were categorized by subsite and anatomic region.ResultsPCa survivors who received EBRT had an increased risk of developing a solid SPC (SIR=1.08; 1.05-1.11), especially in patients aged <70 years (SIR=1.13; 1.09-1.16). Pelvic SPC risks were increased (SIR=1.28; 1.23-1.34), with no obvious differences between the three EBRT eras. Non-pelvic SPC were only significantly increased in the AdvRT era (SIR=1.08; 1.02-1.14), in particular for the 1-5 year follow-up period. Comparing the EBRT cohort to the prostatectomy cohort, again an increased pelvic SPC risk was found for all EBRT periods (sHRs= 1.61, 1.47-1.76). Increased non-pelvic SPC risks were present for all RT eras and highest for the AdvRT period (sHRs=1.17, 1.06-1.29).ConclusionSPC risk in patients with EBRT is increased and remained throughout the different EBRT eras. The risk of developing a SPC outside the pelvic area changed unfavorably in the AdvRT era. Prolonged follow-up is needed to confirm this observation. Whether this is associated with increased irradiated low-dose volumes and scatter, or other changes in clinical EBRT practice, is the subject of further research.

Project description:Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (>10 MV vs ?10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients.The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer.During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher- and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT.Advanced treatment planning may have reduced rectal cancer risks in prostate cancer survivors by approximately 3 cases per 1000 after 15 years. Despite concerns about the neutron doses, we did not find evidence that higher energy therapy was associated with increased second cancer risks.

Project description:BackgroundSecond primary cancers (SPCs) are increasing due to improving survival in first primary cancers. Previous studies on SPCs in renal cell carcinoma (RCC) have focused on treatment and other risk factors, but data of RCC as an SPC are scarce.ObjectiveIn this study, we want to elucidate the risk for any SPC after RCC, and in reverse order, for RCC as an SPC after any cancer. We additionally consider how family histories influence the risks.Design setting and participantsPatient data were obtained from the Swedish Cancer Registry from years 1990 through 2015, and family data were obtained from the Multigeneration Register.Outcome measurements and statistical analysisWe employed standardized incidence ratios to estimate bidirectional relative risks of subsequent cancer associated with RCC.Results and limitationsWe identified 17 587 RCCs (60% in male patients). The highest increases for SPCs were observed for nervous system hemangioblastoma (HB; 26.8), adrenal (12.09) tumors, and renal pelvic cancer (6.32). In the reverse order, RCC as an SPC, nervous system HB (17.01), and adrenal tumors (15.34) were associated with the highest risks. Risks for many other sites (12 sites and subsites) were increased bidirectionally. For women, a total of seven sites and subsites were increased bidirectionally, and many were shared with men. The only significant sex difference in SPCs was the higher lung cancer risk in women (2.41) than in men (1.28). Patients with a family history of HBs or of prostate, colorectal and lung cancers showed high risks of these cancers as SPCs after RCC. Family history accounted for 30% of prostate cancers after RCC.ConclusionsThe bidirectional study design was able to suggest risk factors for SPCs and offered a clinical take-home message urging to consider strategies for early detection and prevention of SPCs. Readily available information on lifestyle (eg, smoking) and family history (eg, prostate cancer) may reveal targets for risk reduction with prognostic benefits.Patient summaryClose to 10% of kidney cancer patients develop another cancer. The cause for these other cancers may not depend on kidney cancer.

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.

Dataset Information

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

Purpose

Material and methods

Results

Conclusion

Publications

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

Similar Datasets

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