Dataset Information

Comparing second cancer risk for multiple radiotherapy modalities in survivors of hodgkin lymphoma.

ABSTRACT:

Objectives

To assess if excess absolute risk (EAR) of radiation-induced solid cancer can be used to rank radiotherapy plans for treatment of Hodgkin lymphoma (HL) in a statistically significant way.

Methods

EAR models, calibrated with data from the Life Span Study and HL survivors, have been incorporated into a voxelised risk-calculation software, which is used to compare four treatment modalities planned for five virtual HL patients. Organ-specific parameters are generated repeatedly in a Monte Carlo fashion to model their uncertainties. This in turn enables a quantitative estimation of the EAR uncertainties.

Results

Parameter-driven uncertainties on total EAR are around 13%, decreasing to around 2-5% for relative EAR comparisons. Total EAR estimations indicate that intensity modulated proton therapy decreases the average risk by 40% compared to the intensity modulated radiation therapy plan, 28% compared to the volumetric modulated arc therapy plan whereas the three-dimensional conformal radiation therapy plan is equivalent within the uncertainty.

Conclusion

Relative EAR is a useful metric for distinguishing between radiotherapy plans in terms of second cancer risk.

Advances in knowledge

Relative EAR is not dominated by model or parameter uncertainties and can be used to guide the choice of radiotherapy for HL patients.

SUBMITTER: Timlin C

PROVIDER: S-EPMC8506169 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Comparing second cancer risk for multiple radiotherapy modalities in survivors of hodgkin lymphoma.

Timlin Claire C Loken James J Kruse Jon J Miller Robert R Schneider Uwe U

The British journal of radiology 20210409 1121

<h4>Objectives</h4>To assess if excess absolute risk (EAR) of radiation-induced solid cancer can be used to rank radiotherapy plans for treatment of Hodgkin lymphoma (HL) in a statistically significant way.<h4>Methods</h4>EAR models, calibrated with data from the Life Span Study and HL survivors, have been incorporated into a voxelised risk-calculation software, which is used to compare four treatment modalities planned for five virtual HL patients. Organ-specific parameters are generated repeat ...[more]

PMID: 33237825

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Project description:BackgroundHodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups.MethodsThe Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG).ResultsOverall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG).ConclusionsColorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy.ImpactColorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.

Project description:ImportanceHodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.ObjectiveTo quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.Design, setting, and participantsA nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.ExposuresMean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.Main outcomes and measuresExcess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.ResultsThe study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.Conclusions and relevanceThis nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.

Dataset Information

Comparing second cancer risk for multiple radiotherapy modalities in survivors of hodgkin lymphoma.

Objectives

Methods

Results

Conclusion

Advances in knowledge

Publications

Comparing second cancer risk for multiple radiotherapy modalities in survivors of hodgkin lymphoma.

Similar Datasets

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