publications
2025
January
- Building Absolute Breast Cancer Risk Prediction Models for Women Treated with Chest Radiation for Hodgkin LymphomaJournal of the Royal Statistical Society Series C: Applied Statistics, Jan 2025
We built models to predict absolute breast cancer (BC) risk in women treated with radiotherapy for Hodgkin lymphoma (HL). We first estimated relative risks (RRs) for risk factors, including radiation dose to 10 breast segments to accommodate heterogeneity of treatment effects, using a case-control sample nested in an HL survivor cohort. To estimate RRs of case-control matching factors we developed novel weighting approaches. We then combined RRs with age-specific BC incidence and competing mortality rates from the HL survivor cohort and a population-based registry, accommodating differences between them. We compared the performance of models using segment-specific doses with using mean dose only.
- Prediction of Breast Cancer Risk for Adolescents and Young Adults with Hodgkin LymphomaSander Roberti, Flora E van Leeuwen, Ibrahima Diallo, Florent de Vathaire, Michael Schaapveld, Wendy M Leisenring, Rebecca M Howell, Gregory T Armstrong, Chaya S Moskowitz, Susan A Smith, Berthe M P Aleman, Inge M Krul, Nicola S Russell, Ruth M Pfeiffer, and Michael HauptmannJNCI: Journal of the National Cancer Institute, Jan 2025
Although female survivors of Hodgkin lymphoma (HL) have an increased risk of breast cancer (BC), no BC risk prediction model is available. We developed such models incorporating mean radiation dose to the breast or breast quadrant-specific radiation doses.Relative risks and age-specific incidence for BC and competing events (mortality or other subsequent cancer) were estimated from 1194 Dutch 5-year HL survivors, treated at ages 11-40 during 1965-2000. Predictors were doses to 10 breast segments or mean breast radiation dose, BC family history, year of and age at HL diagnosis, and ages at menopause and first live birth. Models were independently validated using US Childhood Cancer Survivor Study cohort participants.Predicted absolute BC risks 25 years after HL diagnosis ranged from 1.0% for survivors diagnosed at ages 20-24 with less than 10 Gy mean breast radiation dose and who were menopausal 5 years after HL diagnosis, to 22.0% for survivors 25-29 years at diagnosis, with at least 25 Gy mean breast dose and no menopause within 5 years. In external validation, the observed/expected BC case ratio was 1.19 (95% confidence interval 0.97 to 1.47) for the breast segment-specific dose model, and 1.29 (1.05 to 1.60) for the mean breast dose model. The areas under the receiver operating characteristic curve were 0.68 (0.63 to 0.74) and 0.68 (0.62 to 0.73), respectively.Breast segment-specific or mean breast radiation dose with personal and clinical characteristics predicted absolute BC risk in HL survivors with moderate discrimination but good calibration, rendering the models useful for clinical decision-making.
- Radiation Doses to the Breast and Predicted Breast Cancer Risk among Patients Treated for Hodgkin Lymphoma with Modern RadiotherapySander Roberti, Nicola S. Russell, Ruth M. Pfeiffer, Inge M. Krul, Florent Vathaire, Cristina Veres, Ibrahima Diallo, Cécile P. M. Janus, Joan Penninkhof, René Vernhout, André Buchali, Eyck Blank, Flora E. van Leeuwen, and Michael HauptmannInternational Journal of Radiation Oncology, Biology, Physics, Jan 2025
2023
December
- Development and Multicenter Validation of a Multiparametric Imaging Model to Predict Treatment Response in Rectal CancerNiels W. Schurink, Simon R. van Kranen, Joost J. M. van Griethuysen, Sander Roberti, Petur Snaebjornsson, Frans C. H. Bakers, Shira H. de Bie, Gerlof P. T. Bosma, Vincent C. Cappendijk, Remy W. F. Geenen, Peter A. Neijenhuis, Gerald M. Peterson, Cornelis J. Veeken, Roy F. A. Vliegen, Femke P. Peters, Nino Bogveradze, Najim el Khababi, Max J. Lahaye, Monique Maas, Geerard L. Beets, Regina G. H. Beets-Tan, and Doenja M. J. LambregtsEuropean Radiology, Dec 2023
To develop and validate a multiparametric model to predict neoadjuvant treatment response in rectal cancer at baseline using a heterogeneous multicenter MRI dataset.
February
- Association of Radiation and Procarbazine Dose with Risk of Colorectal Cancer among Survivors of Hodgkin LymphomaYvonne M. Geurts, Rebecca Shakir, Georgios Ntentas, Sander Roberti, Marianne C. Aznar, Katinka M. John, Johanna Ramroth, Cécile P. M. Janus, Augustinus D. G. Krol, Judith M. Roesink, Richard W. M. van der Maazen, Josée M. Zijlstra, Sarah C. Darby, Berthe M. P. Aleman, Flora E. van Leeuwen, David J. Cutter, and Michael SchaapveldJAMA Oncology, Feb 2023
Hodgkin 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.To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.A 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.Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.Excess 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.The 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.This 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.
2022
October
- Accurate Staging of Non-Metastatic Colon Cancer with CT: The Importance of Training and Practice for Experienced Radiologists and Analysis of Incorrectly Staged CasesS. van de Weerd, E. Hong, I. van den Berg, J. W. Wijlemans, J. van Vooren, M. W. Prins, F. J. Wessels, B. C. Heeres, S. Roberti, J. Nederend, J. H. J. M. van Krieken, J. M. L. Roodhart, R. G. H. Beets-Tan, and J. P. MedemaAbdominal Radiology, Oct 2022
To investigate whether locoregional staging of colon cancer by experienced radiologists can be improved by training and feedback to minimize the risk of over-staging into the context of patient selection for neoadjuvant therapy and to identify potential pitfalls of CT staging by characterizing pathologic traits of tumors that remain challenging for radiologists.
September
- Radiotherapy-Related Dose and Irradiated Volume Effects on Breast Cancer Risk among Hodgkin Lymphoma SurvivorsSander Roberti, Flora E van Leeuwen, Cécile M Ronckers, Inge M Krul, Florent de Vathaire, Cristina Veres, Ibrahima Diallo, Cécile P M Janus, Berthe M P Aleman, Nicola S Russell, and Michael HauptmannJNCI: Journal of the National Cancer Institute, Sep 2022
Background: Breast cancer (BC) risk is increased among Hodgkin lymphoma (HL) survivors treated with chest radiotherapy. Case-control studies showed a linear radiation dose-response relationship for estimated dose to the breast tumor location. However, these relative risks cannot be used for absolute risk prediction of BC anywhere in the breasts. Furthermore, the independent and joint effects of radiation dose and irradiated volumes are unclear. Therefore, we examined the effects of mean breast dose and various dose-volume parameters on BC risk in HL patients. Methods: We conducted a nested casecontrol study of BC among 5-year HL survivors (173 case patients, 464 matched control patients). Dose-volume histograms were obtained from reconstructed voxel-based 3-dimensional dose distributions. Summary parameters of dose-volume histograms were studied next to mean and median breast dose, Gini index, and the new dose metric mean absolute difference of dose, using categorical and linear excess odds ratio (EOR) models. Interactions between dose-volume parameters and mean dose were also examined. Results: Statistically significant linear dose-response relationships were observed for mean breast dose (EOR per Gy \frac14 0.19, 95% confidence interval [CI] \frac14 0.05 to 1.06) and median dose (EOR/Gy \frac14 0.06, 95% CI \frac14 0.02 to 0.19), with no statistically significant curvature. All metrics except Gini and mean absolute difference were positively correlated with each other. These metrics all showed similar patterns of dose-response that were no longer statistically significant when adjusting for mean dose. No statistically significant modification of the effect of mean dose was observed. Conclusion: Mean breast dose predicts subsequent BC risk in long-term HL survivors.
March
- Sources of Variation in Multicenter Rectal MRI Data and Their Effect on Radiomics Feature ReproducibilityNiels W. Schurink, Simon R. van Kranen, Sander Roberti, Joost J. M. van Griethuysen, Nino Bogveradze, Francesca Castagnoli, Najim el Khababi, Frans C. H. Bakers, Shira H. de Bie, Gerlof P. T. Bosma, Vincent C. Cappendijk, Remy W. F. Geenen, Peter A. Neijenhuis, Gerald M. Peterson, Cornelis J. Veeken, Roy F. A. Vliegen, Regina G. H. Beets-Tan, and Doenja M. J. LambregtsEuropean Radiology, Mar 2022
To investigate sources of variation in a multicenter rectal cancer MRI dataset focusing on hardware and image acquisition, segmentation methodology, and radiomics feature extraction software.
January
- ADC Values of Cytologically Benign and Cytologically Malignant 18 F-FDG PET-Positive Lymph Nodes of Head and Neck Squamous Cell CarcinomaPetra K. de Koekkoek-Doll, Sander Roberti, Laura Smit, Wouter V. Vogel, Regina Beets-Tan, Michiel W. van den Brekel, and Jonas CastelijnsCancers, Jan 2022
Nodal staging (N-staging) in head and neck squamous cell carcinoma (HNSCC) is essential for treatment planning and prognosis. 18F-fluordeoxyglucose positron emission tomography (FDG-PET) has high performance for N-staging, although the distinction between cytologically malignant and reactive PET-positive nodes, and consequently, the selection of nodes for ultrasound-guided fine needle aspiration cytology (USgFNAC), is challenging. Diffusion-weighted magnetic resonance imaging (DW-MRI) can help to detect nodal metastases. We aim to investigate the potential of the apparent diffusion coefficient (ADC) as a metric to distinguish between cytologically reactive and malignant PET-positive nodes in order to improve node selection criteria for USgFNAC. PET-CT, real-time image-fused USgFNAC and DW-MRI to calculate ADC were available for 78 patients offered for routine N-staging. For 167 FDG-positive nodes, differences in the ADC between cytologically benign and malignant PET-positive nodes were evaluated, and both were compared to the ADC values of PET-negative reference nodes. Analyses were also performed in subsets of nodes regarding HPV status. A mild negative correlation between SUVmax and ADC was found. No significant differences in ADC values were observed between cytologically malignant and benign PET-positive nodes overall. Within the subset of non-HPV-related nodes, ADCb0-200-1000 was significantly lower in cytologically malignant PET-positive nodes when compared to benign PET-positive nodes. ADCb0-1000 and ADCb0-200-1000 were significantly lower (p = 0.018, 0.016, resp.) in PET-negative reference nodes than in PET-positive nodes. ADC was significantly higher in PET-negative reference nodes than in PET-positive nodes. The non-HPV-related subgroup showed significantly (p = 0.03) lower ADC values in cytologically malignant than in cytologically benign PET-positive nodes, which should help inform the node selection procedure for puncture.
2021
September
- Studying Local Tumour Heterogeneity on MRI and FDG-PET/CT to Predict Response to Neoadjuvant Chemoradiotherapy in Rectal CancerNiels W. Schurink, Simon R. van Kranen, Maaike Berbee, Wouter van Elmpt, Frans C. H. Bakers, Sander Roberti, Joost J. M. van Griethuysen, Lisa A. Min, Max J. Lahaye, Monique Maas, Geerard L. Beets, Regina G. H. Beets-Tan, and Doenja M. J. LambregtsEuropean Radiology, Sep 2021
To investigate whether quantifying local tumour heterogeneity has added benefit compared to global tumour features to predict response to chemoradiotherapy using pre-treatment multiparametric PET and MRI data.
August
- Bias Correction for Estimates from Linear Excess Relative Risk Models in Small Case-Control StudiesStatistics in Medicine, Aug 2021
- Predicting Local Tumour Progression after Ablation for Colorectal Liver Metastases: CT-based Radiomics of the Ablation ZoneF. C. R. Staal, M. Taghavi, D. J. van der Reijd, F. M. Gomez, F. Imani, E. G. Klompenhouwer, D. Meek, S. Roberti, M. de Boer, D. M. J. Lambregts, R. G. H. Beets-Tan, and M. MaasEuropean Journal of Radiology, Aug 2021
Purpose To assess whether CT-based radiomics of the ablation zone (AZ) can predict local tumour progression (LTP) after thermal ablation for colorectal liver metastases (CRLM). Materials and methods Eighty-two patients with 127 CRLM were included. Radiomics features (with different filters) were extracted from the AZ and a 10 mm periablational rim (PAR)on portal-venous-phase CT up to 8 weeks after ablation. Multivariable stepwise Cox regression analyses were used to predict LTP based on clinical and radiomics features. Performance (concordance [c]-statistics) of the different models was compared and performance in an ‘independent’ dataset was approximated with bootstrapped leave-one-out-cross-validation (LOOCV). Results Thirty-three lesions (26 %) developed LTP. Median follow-up was 21 months (range 6-115). The combined model, a combination of clinical and radiomics features, included chemotherapy (HR 0.50, p\,= 0.024), cT-stage (HR 10.13, p\,= 0.016), lesion size (HR 1.11, p\,=\,<0.001), AZ_Skewness (HR 1.58, p\,= 0.016), AZ_Uniformity (HR 0.45, p\,= 0.002), PAR_Mean (HR 0.52, p\,= 0.008), PAR_Skewness (HR 1.67, p\,= 0.019) and PAR_Uniformity (HR 3.35, p\,< 0.001) as relevant predictors for LTP. The predictive performance of the combined model (after LOOCV) yielded a c-statistic of 0.78 (95 %CI 0.65-0.87), compared to the clinical or radiomics models only (c-statistic 0.74 (95 %CI 0.58-0.84) and 0.65 (95 %CI 0.52-0.83), respectively). Conclusion Combining radiomics features with clinical features yielded a better performing prediction of LTP than radiomics only. CT-based radiomics of the AZ and PAR may have potential to aid in the prediction of LTP during follow-up in patients with CRLM.
July
- Pre-Treatment Prediction of Early Response to Chemoradiotherapy by Quantitative Analysis of Baseline Staging FDG-PET/CT and MRI in Locally Advanced Cervical CancerLisa A Min, Leanne LGC Ackermans, Marlies E Nowee, Joost JW Griethuysen, Sander Roberti, Monique Maas, Wouter V Vogel, Regina GH Beets-Tan, and Doenja MJ LambregtsActa Radiologica, Jul 2021
BackgroundEarly prediction of response to concurrent chemoradiotherapy (cCRT) could aid to further optimize treatment regimens for locally advanced cervical cancer (LACC) in the future.PurposeTo explore whether quantitative parameters from baseline (pre-therapy) magnetic resonance imaging (MRI) and FDG-PET/computed tomography (CT) have potential as predictors of early response to cCRT.Material and MethodsForty-six patients with LACC undergoing cCRT after staging with FDG-PET/CT and MRI were retrospectively analyzed. Primary tumor volumes were delineated on FDG-PET/CT, T2-weighted (T2W)-MRI and diffusion-weighted MRI (DWI) to extract the following quantitative parameters: T2W volume; T2W signalmean; DWI volume; ADCmean; ADCSD; MTV42%; and SUVmax. Outcome was the early treatment response, defined as the residual tumor volume on MRI 3?4 weeks after start of external beam radiotherapy with chemotherapy (before the start of brachytherapy): patients with a residual tumor volume <10 cm3 were classified as early responders. Imaging parameters were analyzed together with FIGO stage to assess their performance to predict early response, using multivariable logistic regression analysis with bi-directional variable selection. Leave-one-out cross-validation with bootstrapping was used to simulate performance in a new, independent dataset.ResultsT2W volume (OR 0.94, P?=?0.003) and SUVmax (OR 1.15, P?=?0.18) were identified as independent predictors in multivariable analysis, rendering a model with an AUC of 0.82 in the original dataset, and AUC of 0.68 (95% CI 0.41?0.81) from cross-validation.ConclusionAlthough the predictive performance achieved in this small exploratory dataset was limited, these preliminary data suggest that parameters from baseline MRI and FDG-PET/CT (in particular pre-therapy tumor volume) may contribute to prediction of early response to cCRT in cervical cancer.
February
- Locoregional CT Staging of Colon Cancer: Does a Learning Curve Exist?Eun Kyoung Hong, Francesca Castagnoli, Nicolo Gennaro, Federica Landolfi, Carlos Perez-Serrano, Ieva Kurilova, Sander Roberti, and Regina Beets-TanAbdominal Radiology, Feb 2021
To evaluate the learning curve for locoreginal staging of colon cancer in radiologist trainees.
January
- Value of Assessing Peripheral Vascularization with Micro-Flow Imaging, Resistive Index and Absent Hilum Sign as Predictor for Malignancy in Lymph Nodes in Head and Neck Squamous Cell CarcinomaPetra K. de Koekkoek-Doll, Sander Roberti, Michiel W. van den Brekel, Monique Maas, Laura Smit, Regina Beets-Tan, and Jonas CastelijnsCancers, Jan 2021
Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.
2020
October
- Dose-Volume Effects of Breast Cancer Radiation Therapy on the Risk of Second Oesophageal CancerNeige Journy, Sara J. Schonfeld, Michael Hauptmann, Sander Roberti, Rebecca M. Howell, Susan A. Smith, Leila Vaalavirta, Marilyn Stovall, Flora E. van Leeuwen, Rita E. Weathers, David Hodgson, Ethel S. Gilbert, Amy Berrington de Gonzalez, and Lindsay M. MortonRadiotherapy and Oncology, Oct 2020
Purpose To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer. Materials and methods In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943–2003 in five countries, doses to the second primary cancer (DSPC) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5–37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified DSPC-related -risk estimates. Results Among the DVH metrics evaluated, median dose (Dmedian) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for Dmedian increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for DSPC, but there was a borderline significant positive interaction between DSPC and V30 (p = 0.07). Conclusion This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for Dmedian with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to Dmedian and V30 could potentially further reduce the risk of oesophageal cancer.
May
- Value of Combined Multiparametric MRI and FDG-PET/CT to Identify Well-Responding Rectal Cancer Patients before the Start of Neoadjuvant ChemoradiationNiels W. Schurink, Lisa A. Min, Maaike Berbee, Wouter van Elmpt, Joost J. M. van Griethuysen, Frans C. H. Bakers, Sander Roberti, Simon R. van Kranen, Max J. Lahaye, Monique Maas, Geerard L. Beets, Regina G. H. Beets-Tan, and Doenja M. J. LambregtsEuropean Radiology, May 2020
To explore the value of multiparametric MRI combined with FDG-PET/CT to identify well-responding rectal cancer patients before the start of neoadjuvant chemoradiation.
2019
December
- Integrated versus Separate Reading of F-18 FDG-PET/CT and MRI for Abdominal Malignancies – Effect on Staging Outcomes and Diagnostic ConfidenceLisa A. Min, Wouter V. Vogel, Max J. Lahaye, Monique Maas, Maarten L. Donswijk, Erik Vegt, Miranda Kusters, Henry J. Zijlmans, Katarzyna Jóźwiak, Sander Roberti, Regina G. H. Beets-Tan, and Doenja M. J. LambregtsEuropean Radiology, Dec 2019
Abdominal cancer patients increasingly undergo multimodality imaging. This study evaluates effects of integrated reading of PET/CT and abdominal MRI on staging outcomes and diagnostic confidence compared to “routine” separate reading.