Guido Lammering

Maastricht Universitair Medisch Centrum, Maestricht, Limburg, Netherlands

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Publications (128)567.43 Total impact

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    ABSTRACT: Personalized treatments based on predictions for patient outcome require early characterization of a rectal cancer patient's sensitivity to treatment. This study has two aims: (1) identify the main patterns of recurrence and response to the treatments (2) evaluate pathologic complete response (pCR) and two-year disease-free survival (2yDFS) for overall survival (OS) and their potential to be relevant intermediate endpoints to predict. Pooled and treatment subgroup analyses were performed on five large European rectal cancer trials (2795 patients), who all received long-course radiotherapy with or without concomitant and/or adjuvant chemotherapy. The ratio of distant metastasis (DM) and local recurrence (LR) rates was used to identify patient characteristics that increase the risk of recurrences. The DM/LR ratio decreased to a plateau in the first 2years, revealing it to be a critical follow-up period. According to the patterns of recurrences, three patient groups were identified: 5-15% had pCR and were disease free after 2years (excellent prognosis), 65-75% had no pCR but were disease free (good prognosis) and 15-30% had neither pCR nor 2yDFS (poor prognosis). Compared with pCR, 2yDFS is a stronger predictor of OS. To adapt treatment most efficiently, accurate prediction models should be developed for pCR to select patients for organ preservation and for 2yDFS to select patients for more intensified treatment strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Radiotherapy and Oncology 02/2015; DOI:10.1016/j.radonc.2015.02.001
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    ABSTRACT: In many European countries, short-term 5x5 Gy radiotherapy has become the standard preoperative treatment for patients with resectable rectal cancer. Individualized risk assessment might allow a better selection of patients who will benefit from postoperative treatment and intensified follow-up. From patient data from three European rectal cancer trials (N=2881) we developed multivariate cox nomograms reflecting the risk for local recurrence (LR), distant metastases (DM) and overall survival (OS). Evaluated variables were age, gender, tumour distance from the anal verge, the use of radiotherapy, surgical technique (TME/conventional surgery), surgery type (LAR/APR), time from randomization to surgery, residual disease (R0 vs R1+2), pT-stage, pN-stage and surgical complications. Pathological T- and N-status are of vital importance for an accurate prediction of local recurrence, distant metastases and overall survival. Short-course radiotherapy reduces local recurrence rate. The developed nomograms are capable of predicting events with a validation c-index of 0.79 (LR), 0.76 (DM) and 0.75 (OS). The proposed stratification in risk groups allowed significant distinction between Kaplan-Meier curves for outcome. The developed nomograms can contribute to better individual risk prediction for local recurrence, distant metastases and overall survival for patients operated on rectal cancer. The practicality of the defined risk groups makes decision support in the consulting room feasible, assisting physicians to select patients for adjuvant therapy or intensified follow-up. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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    ABSTRACT: To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging. Prospective data (i.a. THUNDER trial) were used to train (N=112, MAASTRO Clinic) and validate (N=78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUVmax, SUVmean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUVmean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Radiotherapy and Oncology 11/2014; 113(2). DOI:10.1016/j.radonc.2014.11.002
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    ABSTRACT: Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for inoperable patients or patients with irresectable liver tumors. Outcome and toxicity were evaluated retrospectively in this single-institution patient cohort. Between 2010 and 2014, 39 lesions were irradiated in 33 consecutive patients (18 male, 15 female, median age of 68 years). All the lesions were liver metastases (n = 34) or primary hepatocellular carcinomas (n = 5). The patients had undergone four-dimensional respiration-correlated PET-CT for treatment simulation to capture tumor motion. We analyzed local control with a focus on CT-based response at three months, one year and two years after treatment, looking at overall survival and the progression pattern. All patients were treated with hypofractionated image-guided stereotactic radiotherapy. The equivalent dose in 2 Gy fractions varied from 62.5 Gy to 150 Gy, delivered in 3-10 fractions (median dose 93.8 Gy, alpha/beta = 10). The CT-based regression pattern three months after radiotherapy revealed partial regression in 72.7% of patients with a complete remission in 27.3% of the cases. The site of first progression was predominantly distant. One- and two-year overall survival rates were 85.4% and 68.8%, respectively. No toxicity of grade 2 or higher according to the NCI Common Terminology Criteria for Adverse Events v4.0 was observed. SABR is a safe and efficient treatment for selected inoperable patients or irresectable tumors of the liver. Future studies should combine SABR with systemic treatment acting in synergy with radiation, such as immunological interventions or hypoxic cell radiosensitizers to prevent distant relapse. Copyright © 2014 Elsevier Ltd. All rights reserved.
    European Journal of Surgical Oncology 11/2014; 41(2). DOI:10.1016/j.ejso.2014.10.053
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    ABSTRACT: Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer.
    Radiotherapy and Oncology 04/2014; 111(2). DOI:10.1016/j.radonc.2014.03.006
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    ABSTRACT: To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable esophageal cancer. Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy. Reproducibility of apparent diffusion coefficient (ADC) measurements by manual (freehand) and semi-automated volumetric methods was assessed. Interobserver reproducibility for the assessment of mean tumor ADC by the manual measurement method was good, with an ICC of 0.69 (95% CI, 0.36 to 0.85; P = 0.001). Interobserver reproducibility for the assessment of mean tumor ADC by the semi-automated volumetric measurement method was very good, with an ICC of 0.96 (95% CI, 0.91 to 0.98; P<0.001). Semi-automated volumetric ADC measurements have higher reproducibility than manual ADC measurements in assessing tumor response to chemoradiotherapy in patients with esophageal adenocarcinoma.
    PLoS ONE 04/2014; 9(4):e92211. DOI:10.1371/journal.pone.0092211
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    ABSTRACT: New prognostic markers may be of value in determining survival and informing decisions of adjuvant treatment in the heterogeneous group of soft tissue sarcomas known as malignant fibrous sarcomas (MFS). Increased CD44 expression has been associated with a better outcome in cancers such as bladder tumors and could potentially relate to cell-cell interaction as a marker for potential invasion/metastasis. The aim of this pilot study was to determine if there is a correlation between the expression rate of CD44 in adult patients with MFS and clinical outcomes. The clinical outcome of 34 adult MFS patients (19 males and 15 females, average age 62 years, median 63 years, range: 38-88 years) who underwent surgical treatment were evaluated. Twenty-five of these patients had additional adjuvant radiotherapy. Extracted RNA from sarcoma tissues was used to measure the transcripts of CD44s (standard form) and isoform expression.The pooled data for each variant of CD44 was divided in half at the median expression value into two equally sized groups (low and high). Survival modeling and multivariate analysis were used with these two groups to determine if there were differences in survival times and whether this was independent of known factors such as tumor stage/grade, patient age and resection margin status. High CD44s and low of CD44v6 expression significantly correlated with an improved outcome (P <0.05 and P <0.02, respectively) whereas CD44v8 and hCD44 (isoforms) did not. Differences in survival were apparent within 6-12 months of operation with >30% difference in survival between low/high expressions at 5 years. These finding were independent of the other measured MFS survival predictors, though the group was homogenous. High CD44s and low CD44v6 expression may be an independent predictor of improved survival in MFS patients in this pilot data. This is contrary to other MFS data, which did not account for the CD44 isoforms but is confirmed by data from other cancer types. Further investigation is needed to confirm CD44 isoform expression data as a relevant survival biomarker and whether it could be used to inform clinical decisions such as adjuvant therapy.
    02/2014; 19(1):6. DOI:10.1186/2047-783X-19-6
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    ABSTRACT: Purpose/objective Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer. Material/methods 295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol (NCT01067872). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages). Results 276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response. Conclusion CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of earlier developed prediction models using clinical variables and PET-information. The new model could help to an early adaptation of treatment in rectal cancer patients.
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    ABSTRACT: A previous study showed promising results for gadofosveset-trisodium as a lymph node magnetic resonance imaging (MRI) contrast agent in rectal cancer. The aim of this study was to prospectively confirm the diagnostic performance of gadofosveset MRI for nodal (re)staging in rectal cancer in a second patient cohort. Seventy-one rectal cancer patients were prospectively included, of whom 13 (group I) underwent a primary staging gadofosveset MRI (1.5-T) followed by surgery (± preoperative 5 × 5 Gy) and 58 (group II) underwent both primary staging and restaging gadofosveset MRI after a long course of chemoradiotherapy followed by surgery. Nodal status was scored as (y)cN0 or (y)cN+ by two independent readers (R1, R2) with different experience levels. Results were correlated with histology on a node-by-node basis. Sensitivity, specificity and area under the receiver operating characteristics curve (AUC) were 94 %, 79 % and 0.89 for the more experienced R1 and 50 %, 83 % and 0.74 for the non-experienced R2. R2's performance improved considerably after a learning curve, to an AUC of 0.83. Misinterpretations mainly occurred in nodes located in the superior mesorectum, nodes located in between vessels and nodes containing micrometastases. This prospective study confirms the good diagnostic performance of gadofosveset MRI for nodal (re)staging in rectal cancer. • Gadofosveset-enhanced MRI shows high performance for nodal (re)staging in rectal cancer. • Gadofosveset MRI may facilitate better selection of patients for personalised treatment. • Results can be reproduced by non-expert readers. • Experience of 50-60 cases is required to achieve required expertise level. • Main pitfalls are nodes located between vessels and nodes containing micrometastases.
    European Radiology 09/2013; DOI:10.1007/s00330-013-3016-6
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    ABSTRACT: The implementation of neoadjuvant chemoradiotherapy (CRT) in esophageal cancer (EC) patients has led to improved survival rates. Worldwide, different CRT regimens are applied. It is unknown how these regimens relate to each other regarding efficacy. Therefore, the aim of this study was to determine the preferred regimen regarding toxicity of, response to CRT, and long-term survival after esophagectomy in EC patients. EC patients in two centers who underwent CRT with different regimens prior to surgery were included in this study. CRT consisted of 50.4Gy combined with two cycles of cisplatin and 5-FU(center A), or 41.4Gy combined with five cycles of carboplatin and paclitaxel (center B). Toxicity, response to therapy and long-term survival were compared between groups. One hundred sisty-five patients were included. Forty-one percent of patients in center A developed ≥1 toxicity ≥ grade 3 versus 25% in center B (P = 0.025). CRT with a cisplatin-based regimen was an independent predictor for development of toxicity ≥ grade 3 (P = 0.043). There were no differences in response between both regimens (P = 0.904). Three-year survival was 61% (A) versus 57% (B) (P = 0.725). The carboplatin/paclitaxel/41.4Gy regimen causes less toxicity compared to the cisplatin/5-FU/50.4Gy regimen with nonsignificant differences in response rates and long-term survival; therefore our results support this regimen to be the preferred regimen for EC patients.
    Diseases of the Esophagus 09/2013; 27(4). DOI:10.1111/dote.12110
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    ABSTRACT: To determine retrospectively the additional value of DWI-MRI toT2-MRI for predicting complete response (ypT0N0 = CR) after chemoradiation-therapy (CRT) in locally advanced rectal cancer. Seventy locally advanced rectal cancer patients underwent CRT followed by restaging MRI and resection. Two readers with different experience levels independently scored T2 images for CR and, in a second reading, combined T2 and DWI. A 5-point confidence-level score was used to generate ROC curves. Areas under the ROC curves (AUC) and interobserver agreement were compared for both readings. Histology served as reference standard. The interobserver agreement increased after addition of DWI from 0.35 to 0.58 but the AUC improved only for the experienced reader (0.77 to 0.89, p = 0.005 vs. 0.74 to 0.70, p > 0.05). Sensitivity and NPV improved from 20-30 % to 40-70 %, respectively 88 % to 91-95 %. Specificity and PPV improved only for the experienced reader (87 to 93 % respectively 27 to 63 %). Adding DWI to T2-MRI improves consistency between readers and has potential to improve readers' accuracy dependent on his/her experience. DWI could be of additional value, particularly in ruling out CR (high NPV), but considering the sub-optimal PPV one should be cautious about relying solely on MRI for the clinical decision to offer a wait-and-see strategy. • Diffusion-weighted magnetic resonance imaging is increasingly used to assess rectal tumours • Adding DWI to T2-MRI potentially improves diagnostic accuracy for identifying complete responders • Adding DWI to T2-MRI improves consistency among readers with different experience levels. • This combination can help rule out complete tumour response. • Patients should not be selected for wait-and-see strategies by MRI alone.
    European Radiology 07/2013; 23(12). DOI:10.1007/s00330-013-2956-1
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    ABSTRACT: PURPOSE: Neoadjuvant chemoradiotherapy is increasingly used in oesophageal cancer patients. In general, small tumours are associated with a survival benefit compared to large tumours. Little is known, however, about the relationship between initial tumour volume and response to chemoradiotherapy. Therefore, the aim of this study was to determine whether the pretherapy metabolic tumour volume (MTV) on diagnostic PET/CT in oesophageal cancer patients is correlated with response to chemoradiotherapy in the resection specimen. METHODS: A consecutive series of patients underwent diagnostic PET/CT scanning prior to chemoradiotherapy and oesophagectomy. MTVs were determined on PET/CT and an automated tumour contour was generated using specified standard uptake value thresholds. Response to chemoradiotherapy was determined in the resection specimen according to the scoring system developed by Mandard et al. Patients were divided into different groups according to response to chemoradiotherapy. RESULTS: Between January 2008 and May 2011 a total of 115 patients underwent an oesophagectomy. The MTV determined on diagnostic PET/CT scans was available in 79 patients. Of these 79 patients, 30 (38 %) showed no residual tumour cells at the location of the primary tumour. Three of these patients presented with residual tumour cells in the lymph nodes; 27 patients (34 %) had a complete pathological response. There was a trend towards a better response in patients with a smaller MTV (p = 0.084). CONCLUSION: This study demonstrated a trend towards a correlation between response to chemoradiotherapy in oesophageal cancer patients and smaller MTVs as determined on diagnostic PET/CT prior to neoadjuvant chemoradiotherapy. However, tumour volumes overlapped between groups, indicating the need for multifactorial parameters as predictors. In addition, a complete local tumour response may be accompanied by residual disease in the regional lymph nodes.
    European Journal of Nuclear Medicine 06/2013; 40(10). DOI:10.1007/s00259-013-2468-x
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    ABSTRACT: BACKGROUND: Long-term survival can be obtained with local treatment of lung metastases from colorectal cancer. However, it is unclear as to what the optimal local therapy is: surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SBRT). METHODS: A systematic review included 27 studies matching with the a priori selection criteria, the most important being ⩾50 patients and a follow-up period of ⩾24months. No SBRT studies were eligible. The review was therefore conducted on 4 RFA and 23 surgical series. RESULTS: Four of the surgical studies were prospective, all others were retrospective. No randomized trial was found. The reporting of data differed between the studies, which led to difficulties in the analyses. Treatment-related mortality rates for RFA and surgery were 0% and 1.4-2.4%, respectively, whereas morbidity rates were reported inconsistently but seemed the lowest for surgery. CONCLUSION: Due to the lack of phase III trials, no firm conclusions can be drawn, although most evidence supports surgery as the most effective treatment option. High-quality trials comparing currently used treatment modalities such as SBRT, RFA and surgery are needed to inform treatment decisions.
    Cancer Treatment Reviews 06/2013; 40(1). DOI:10.1016/j.ctrv.2013.05.004
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    ABSTRACT: BACKGROUND AND PURPOSE: Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. RESULTS: rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10(-8) and 6.9×10(-7) respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers' d=5.0×10(-12) in the replication cohort). CONCLUSIONS: This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.
    Radiotherapy and Oncology 05/2013; 107(3). DOI:10.1016/j.radonc.2013.05.001
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    ABSTRACT: PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. MATERIAL AND METHODS: Twelve patients were treated with chemoradiotherapy to 50.4Gy combined with capecitabine 825mg/m(2) BID. Three dose levels (DL) of nelfinavir were tested: 750mg BID (DL1), 1250mg BID (DL2) and an intermediate level of 1000mg BID (DL3). Surgery was performed between 8 and 10weeks after completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), defined as any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL1, 3 in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In DL2 one patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase elevation and 1 patient had a gr 3 cholangitis with unknown cause. An intermediate dose level was tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 patient gr 3 transaminase elevation and gr 4 post-operative wound complication. Three patients achieved a pathological complete response (pCR). CONCLUSIONS: Nelfinavir 750mg BID was defined as the recommended phase II dose in combination with capecitabine and 50.4Gy pre-operative radiotherapy in rectal cancer. First tumor response evaluations are promising, but a further phase II study is needed to get more information about efficacy of this treatment regimen.
    Radiotherapy and Oncology 05/2013; 107(2). DOI:10.1016/j.radonc.2013.03.023
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    ABSTRACT: PURPOSE: Accurate tumor positioning in stereotactic body radiation therapy (SBRT) of liver lesions is often hampered by motion and setup errors. We combined 3-dimensional ultrasound imaging (3DUS) and active breathing control (ABC) as an image guidance tool. METHODS AND MATERIALS: We tested 3DUS image guidance in the SBRT treatment of liver lesions for 11 patients with 88 treatment fractions. In 5 patients, 3DUS imaging was combined with ABC. The uncertainties of US scanning and US image segmentation in liver lesions were determined with and without ABC. RESULTS: In free breathing, the intraobserver variations were 1.4 mm in left-right (L-R), 1.6 mm in superior-inferior (S-I), and 1.3 mm anterior-posterior (A-P). and the interobserver variations were 1.6 mm (L-R), 2.8 mm (S-I), and 1.2 mm (A-P). The combined uncertainty of US scanning and matching (inter- and intraobserver) was 4 mm (1 SD). The combined uncertainty when ABC was used reduced by 1.7 mm in the S-I direction. For the L-R and A-P directions, no significant difference was observed. CONCLUSION: 3DUS imaging for IGRT of liver lesions is feasible, although using anatomic surrogates in the close vicinity of the lesion may be needed. ABC-based breath-hold in midventilation during 3DUS imaging can reduce the uncertainty of US-based 3D table shift correction.
    International journal of radiation oncology, biology, physics 10/2012; 85(4). DOI:10.1016/j.ijrobp.2012.08.016
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    ABSTRACT: PURPOSE: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. METHODS AND MATERIALS: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. RESULTS: Twelve SNPs identified in the discovery cohort and validated in the replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 × 10(-5) to 6.2 × 10(-4)). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 × 10(-29)). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 × 10(-19)). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. CONCLUSIONS: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.
    International journal of radiation oncology, biology, physics 09/2012; 85(1). DOI:10.1016/j.ijrobp.2012.08.003
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    ABSTRACT: An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.
    Strahlentherapie und Onkologie 08/2012; 188(9):777-81. DOI:10.1007/s00066-012-0162-8
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    ABSTRACT: Background. The objectives of this study were to investigate the predictive value of sequential (18)F-FDG PET scans for pathological tumor response grade (TRG) after preoperative chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC) and the impact of partial volume effects correction (PVC). Methods. Twenty-eight LARC patients were included. Responders and non-responders status were determined in histopathology. PET indices [SUV max and mean, volume and total lesion glycolysis (TLG)] at baseline and their evolution after one and two weeks of PCRT were extracted by delineation of the PET images, with or without PVC. Their predictive value was investigated using Mann-Whitney-U tests and ROC analysis. Results. Within baseline parameters, only SUV(mean) was correlated with response. No evolution after one week was predictive of the response, whereas after two weeks all the parameters except volume were, the best prediction being obtained with TLG (AUC 0.79, sensitivity 63%, specificity 92%). PVC had no significant impact on these results. Conclusion. Several PET indices at baseline and their evolution after two weeks of PCRT are good predictors of response in LARC, with or without PVC, whereas results after one week are suboptimal. Best predictor was TLG reduction after two weeks, although baseline SUV(mean) had smaller but similar predictive power.
    Acta oncologica (Stockholm, Sweden) 08/2012; 52(3). DOI:10.3109/0284186X.2012.702923
  • Radiotherapy and Oncology 05/2012; 103:S234. DOI:10.1016/S0167-8140(12)70923-4

Publication Stats

2k Citations
567.43 Total Impact Points

Institutions

  • 2010–2015
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2014
    • Universitätsklinikum Düsseldorf
      • Klinik und Poliklinik für Strahlentherapie und Radioonkologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2005–2014
    • Maastricht University
      • • GROW School for Oncology & Developmental Biology
      • • Department of Radiotherapy
      • • Department of Radiology
      Maestricht, Limburg, Netherlands
  • 2006–2013
    • Maastro Clinic
      Maestricht, Limburg, Netherlands
  • 1999–2012
    • Heinrich-Heine-Universität Düsseldorf
      • • Faculty of Medicine
      • • Klinik und Poliklinik für Strahlentherapie und Radioonkologie
      Düsseldorf, North Rhine-Westphalia, Germany
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 2011
    • Catholic University of the Sacred Heart
      Milano, Lombardy, Italy
    • University of Coimbra
      Coímbra, Coimbra, Portugal
  • 2009
    • Seoul National University Bundang Hospital
      Sŏul, Seoul, South Korea
  • 2008
    • Hospital Universitario Puerta de Hierro-Majadahonda
      Махадаонда, Madrid, Spain
  • 2000–2004
    • Virginia Commonwealth University
      • Department of Radiation Oncology
      Richmond, VA, United States