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augustinus desiderius krol


a.d.g.krol@lumc.nl

Journal articles

2011
M J J Kuper-Hommel, M L G Janssen-Heijnen, G Vreugdenhil, A D G Krol, H C Kluin-Nelemans, J W W Coebergh, J H J M van Krieken (2011)  Clinical and pathological features of testicular diffuse large B-cell lymphomas; a heterogeneous disease.   Leuk Lymphoma Jul  
Abstract: Abstract Most testicular lymphomas are of diffuse large B-cell (DLBCL) type with an outcome inferior to nodal DLBCL. Within an apparently homogeneous group of testicular DLBCL, small cell components, plasmacytoid differentiation and lymphoepithelial lesions (LEL), features of extranodal marginal zone lymphoma (eMZL) can be identified. The aim of this study was to define the histological features of testicular DLBCL and correlate this with their clinical behavior and outcome. Thirty-six patients with testicular DLBCL (AAS I/II) were identified through the databases of two Dutch regional cancer registries diagnosed between 1981 and 1999. Follow-up for patients alive was more than ten years. Medical records and pathology specimens were reviewed. EMZL features were found in 53% of the cases of localized stage testicular DLBCL. Compared to patients with "pure" DLBCL, patients with DLBCL with eMZL features presented more often with stage 1 disease, normal LDH, smaller tumors and absence of B-symptoms and they responded more favorably to initial treatment. Their median survival was 48 months versus 12 months for "pure" DLBCL (p: 0.87). Features of eMZL are commonly identified in testicular DLBCL and they correlated with a more favorable clinical presentation and better response to initial therapy. However these differences did not reach statistical significance due to small numbers.
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2010
2009
Marie L De Bruin, Lucille D A Dorresteijn, Mars B van't Veer, Augustinus D G Krol, Helena J van der Pal, Arnoud C Kappelle, Willem Boogerd, Berthe M P Aleman, Flora E van Leeuwen (2009)  Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma.   J Natl Cancer Inst 101: 13. 928-937 Jul  
Abstract: BACKGROUND: Information on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored potential pathogenic mechanisms. METHODS: We performed a retrospective cohort study among 2201 five-year survivors of Hodgkin lymphoma treated before age 51 between 1965 and 1995. We compared incidence rates of clinically verified stroke and TIA with those in the general population. We used multivariable Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided. RESULTS: After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population, after prolonged follow-up. The cumulative incidence of ischemic stroke or TIA 30 years after Hodgkin lymphoma treatment was 7% (95% CI = 5% to 8%). Radiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (hazard ratio = 2.5, 95% CI = 1.1 to 5.6 vs without radiotherapy). Treatment with chemotherapy was not associated with an increased risk. Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease, whereas smoking and overweight were not. CONCLUSIONS: Patients treated for Hodgkin lymphoma experience a substantially increased risk of stroke and TIA, associated with radiation to the neck and mediastinum. Physicians should consider appropriate risk-reducing strategies.
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2008
Hans Gelderblom, Pancras C W Hogendoorn, Sander D Dijkstra, Carla S van Rijswijk, Augustinus D Krol, Antonie H M Taminiau, Judith V M G Bovée (2008)  The clinical approach towards chondrosarcoma.   Oncologist 13: 3. 320-329 Mar  
Abstract: This review provides an overview of the histopathology, classification, diagnostic procedures, and therapy of skeletal chondrosarcoma. Chondrosarcomas that arise de novo are primary chondrosarcomas, whereas chondrosarcomas developing superimposed on pre-existing benign cartilage neoplasms such as enchondromas or osteochondromas are referred to as secondary chondrosarcomas. Conventional chondrosarcomas can be categorized according to their location in bone into central, peripheral, and juxtacortical chondrosarcomas. Histological grading is related to prognosis; however, it is also subject to interobserver variability. Rare subtypes of chondrosarcoma, including dedifferentiated, mesenchymal, and clear cell chondrosarcoma, are discussed as well. Magnetic resonance imaging is necessary to delineate the extent of the intraosseous and soft tissue involvement preoperatively. Computed tomography is especially recommended in the pelvis and other flat bones where it may be difficult to discern the pattern of bone destruction and the presence of matrix mineralization. Wide, en-bloc excision is the preferred surgical treatment in intermediate- and high-grade chondrosarcoma. In low-grade chondrosarcoma confined to the bone, extensive intralesional curettage followed by local adjuvant treatment and filling the cavity with bone graft has promising long-term clinical results and satisfactory local control. Chondrosarcomas are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in attempts to achieve local control after incomplete resection. Irradiation with protons or other charged particles seems beneficial in this curative situation. Chemotherapy is only possibly effective in mesenchymal chondrosarcoma, and is of uncertain value in dedifferentiated chondrosarcoma. Potential new systemic treatment targets are being discussed.
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2006
Evert M Noordijk, Patrice Carde, Noëlle Dupouy, Anton Hagenbeek, Augustinus D G Krol, Johanna C Kluin-Nelemans, Umberto Tirelli, Mathieu Monconduit, José Thomas, Houchingue Eghbali, Berthe M P Aleman, Jacques Bosq, Marjeta Vovk, Tom A M Verschueren, Anne-Marie Pény, Théodore Girinsky, John M M Raemaekers, Michel Henry-Amar (2006)  Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.   J Clin Oncol 24: 19. 3128-3135 Jul  
Abstract: PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.
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2003
A D G Krol, S le Cessie, S Snijder, J C Kluin-Nelemans, P M Kluin, E M Noordijk (2003)  Primary extranodal non-Hodgkin's lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry.   Ann Oncol 14: 1. 131-139 Jan  
Abstract: BACKGROUND: The definition of primary extranodal non-Hodgkin's lymphoma (NHL) is a controversial issue, especially in patients where both nodal and extranodal sites are involved. PATIENTS AND METHODS: The impact of different definitions of primary extranodal NHL on incidence and prognosis is explored using data from a population-based NHL registry. RESULTS: Using liberal criteria, 389 (34%) cases were classified as primary extranodal NHL. Overall survival (OS) rates of nodal and extranodal NHL patients defined this way were comparable; however, extranodal NHL patients had a better disease-free survival (DFS). When strict criteria were applied, 231 cases (20%) were classified as primary extranodal NHL. OS and DFS rates of extranodal NHL patients defined this way were superior to nodal NHL patients; however, the difference in OS was reversed after correction for differences in International Prognostic Index and malignancy grade. CONCLUSION: This study illustrates the selection bias that is introduced when a strict definition of primary extranodal NHL, that excludes cases with disseminated disease, is used. Patients with primary extranodal NHL were found to have a superior DFS, irrespective of which definition of primary extranodal NHL was used.
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A D G Krol, S le Cessie, S Snijder, J C Kluin-Nelemans, Ph M Kluin, E M Noordijk (2003)  Non-Hodgkin's lymphoma in the Netherlands: results from a population-based registry.   Leuk Lymphoma 44: 3. 451-458 Mar  
Abstract: The Comprehensive Cancer Centre West (CCCW) population based non-Hodgkin's lymphoma (NHL) registry contains information on all newly diagnosed NHL patients living in the region covered by the CCCW. Patients were entered from June 1st 1981 to December 31st 1989. Follow-up is still ongoing, median follow-up is 113 months (1-191 months) for patients alive. In this study, patient and tumor characteristics, data on patterns of care, response and (relative) survival are described. As follicular lymphomas and diffuse large B-cell lymphomas are the most frequently occurring NHL subtypes in the database, a separate analysis is performed to characterize the clinical picture of these disease entities in the CCCW population. Our data illustrate that NHL patients in the general population are substantially older than patients included in trials and hospital based series. Due to older age, treatment is withheld or adapted for a substantial number of patients. The resulting survival and relative survival rates are a reflection of these choices.
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2001
A D Krol, H W Berenschot, D Doekharan, S Henzen-Logmans, B van der Holt, M B van 't Veer (2001)  Cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy and radiotherapy for stage I intermediate or high grade non-Hodgkin's lymphomas: results of a strategy that adapts radiotherapy dose to the response after chemotherapy.   Radiother Oncol 58: 3. 251-255 Mar  
Abstract: BACKGROUND: A limited number cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy followed by involved field radiotherapy is the treatment of choice for Ann Arbor stage I intermediate or high grade non-Hodgkin's lymphomas (NHL). The optimal radiotherapy dose in this combined modality setting, resulting in maximal disease control with minimal toxicity is unknown. In this retrospective single-center study we evaluated the results of a combined modality treatment strategy that adapts the radiotherapy dose to the response after chemotherapy, and focus on the influence of radiotherapy dose on local control and survival. PATIENTS AND METHODS: One hundred and forty patients with NHL Ann Arbor stages I/IE of intermediate or high grade malignancy received four cycles of CHOP chemotherapy followed by involved field radiotherapy (IF-RT). The radiotherapy dose for patients in complete response (CR) after CHOP was either 26 or 40 Gy. Patients in partial response (PR) after CHOP always received 40 Gy. The influence of the radiotherapy dose on treatment outcome was evaluated for patients in CR at the end of treatment (n=128). RESULTS: CR rates after chemotherapy and after radiotherapy were 67 and 91%, respectively. Seventy-four of the patients in CR after CHOP received 26 Gy, 20 patients in CR after CHOP 40 Gy. All patients in PR after CHOP (n=34) received 40 Gy. The localization of relapse (within or outside the radiation field) did not differ between patients receiving 26 or 40 Gy. Overall survival (OS) at 5 years for patients in CR after CHOP who received 26 and 40 Gy and for patients in PR after CHOP but CR after 40 Gy IF-RT was 76, 100 and 75%, respectively, (P=0.16), disease free survival (DFS) at 5 years 69, 90 and 75%, respectively, (P=0.52). CONCLUSIONS: No statistically significant differences in patterns of relapse or survival were found between patients receiving 26 or 40 Gy IF-RT, however the number of events in all subgroups was small.
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A D Krol, S Le Cessie, S Snijder, J C Kluin-Nelemans, P M Kluin, E M Noorduk (2001)  Waldeyer's ring lymphomas: a clinical study from the Comprehensive Cancer Center West population based NHL registry.   Leuk Lymphoma 42: 5. 1005-1013 Sep/Oct  
Abstract: It is debated whether non-Hodgkin's lymphomas originating in Waldeyer's ring (WR NHL) behave as NHL originating in lymph nodes or share common features with extranodal lymphomas originating in mucosa associated lymphatic tissue (MALT). We analyzed data from a population based NHL registry on patterns of dissemination at diagnosis, response to treatment, patterns of failure and survival of 77 primary Waldeyer's ring Non-Hodgkin's lymphomas (WR NHL) patents. Data of completely staged patients with diffuse large cell lymphomas (DLCL) originating in WR (n=44) were compared with those of patients retrieved from the same registry with DLCL originating in lymph nodes or stomach (the latter as prototype of a lymphoma originating in MALT). Primary WR NHL had favorable risk scores according to the International Prognostic Index (IPI), and responded well to therapy: a complete response (CR) rate of 74% was observed. Disease free survival (DFS) and overall survival (OS) were poor, however (47% and 31% at 10 years, respectively). The comparison of DLCL originating in WR, lymph nodes and stomach revealed that WR and gastric NHL patients shared a restricted pattern of dissemination at diagnosis, in contrast to patients with DLCL originating in lymph nodes. Although not all patients were completely restaged at relapse, analysis of patterns of failure suggested that the gastro-intestinal tract is a preferential site for recurrences, both for WR and gastric DLCL patients. CR rates of WR, nodal and gastric DLCL patients were 77%, 55% and 55% respectively (P=0.03), OS of the three patient subgroups did not differ (33%, 27% and 37% at 10 years). DFS of WR DLCL patients was similar to nodal DLCL patients but inferior to gastric DLCL patients (47%, 48% and 73% at 10 years respectively, P=0.006). After Cox regression analysis the relative relapse risk for patients with WR DLCL when compared to patients with DLCL originating in lymph nodes was 2.01 (C.I. 0.99-4.01, P=0.05), and 3.46 (C.I. 1.32-9.00, P=0.01) when compared to patients with gastric DLCL. The clinical picture of primary WR NHL emerging from this population based study is in agreement with data form hospital based studies. In the comparison of WR DLCL, nodal DLCL and gastric DLCL, the observed patterns of dissemination suggest similarities between WR DLCL and gastric DLCL. The frequent relapses after CR observed for WR DLCL patients, however, indicate that these lymphomas clinically behave as nodal DLCL, and should be treated accordingly.
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2000
M A Hoeve, A D Krol, K Philippo, P W Derksen, R A Veenendaal, E Schuuring, P M Kluin, J H van Krieken (2000)  Limitations of clonality analysis of B cell proliferations using CDR3 polymerase chain reaction.   Mol Pathol 53: 4. 194-200 Aug  
Abstract: BACKGROUND/AIMS: Detection of clonal immunoglobulin heavy chain (IgH) rearrangements by the polymerase chain reaction (PCR) is an attractive alternative to Southern blotting in lymphoma diagnostics. However, the advantages and limitations of PCR in clonality analysis are still not fully appreciated. In this study, clonality was analysed by means of PCR, focusing in particular on the sample size requirements when studying extremely small samples of polyclonal and monoclonal lesions. MATERIALS/METHODS: High resolution complementarity determining region 3 (CDR3) PCR was used to investigate the minimum number of cells and the amount of tissue required for the detection of a polyclonal population, both for fresh cells and formalin fixed, paraffin wax embedded tissue. Subsequently, frozen and paraffin wax embedded samples of 76 B cell lymphoproliferative disorders, 43 of which were tested by means of Southern blotting, were analysed to establish the sensitivity of this assay. These specimens included 12 chronic lymphocytic leukaemias (CLLs), nine mantle cell lymphomas (MCLs), 10 follicular lymphomas (FLs), and 45 mucosa associated lymphoid tissue (MALT) lymphomas. The specificity was tested on reactive lymph nodes (n = 19), tonsils (n = 4), peripheral blood lymphocyte fractions (n = 4), and biopsies with gastritis (n = 21). RESULTS: In reactive tissue, 20 ng of high molecular weight DNA derived from 6.5-9 x 10(3) B cells was sufficient to obtain a polyclonal PCR result. With smaller amounts "pseudoclonality" could be induced. When using paraffin wax blocks, undiluted DNA isolated from tonsillar tissue of at least 1 mm2 was necessary to obtain a polyclonal pattern. The sensitivity required to detect clonality in paraffin wax embedded and frozen tissue by PCR for FL (40% and 60%, respectively) was lower than that for MALT lymphomas (60% and 86%, respectively), CLL (78% and 89%, respectively), and MCL (88% and 100%, respectively). PCR specificity was 96% and 100% for frozen and paraffin wax embedded tissue, respectively. CONCLUSION: The minimum amount of template for CDR3 PCR is approximately 20 ng of high molecular weight DNA or 1 mm3 of B cell rich paraffin wax embedded normal tonsillar tissue, but care has to be taken to avoid pseudoclonality when low numbers of B cells are present. Duplicate or triplicate tests should be performed to avoid misinterpretation. The specificity of the PCR assay is almost 100%, whereas sensitivity depends on a combination of factors, such as lymphoma type and tissue fixation. Because frozen samples yield better results, obtaining fresh material for the PCR assay is recommended, especially when analysing FL and MALT lymphomas.
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F E van Leeuwen, W J Klokman, M B Veer, A Hagenbeek, A D Krol, U A Vetter, M Schaapveld, P van Heerde, J M Burgers, R Somers, B M Aleman (2000)  Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood.   J Clin Oncol 18: 3. 487-497 Feb  
Abstract: PURPOSE: To quantify the long-term risk of second primary cancers (SCs) in patients diagnosed with Hodgkin's disease (HD) during adolescence or young adulthood. PATIENTS AND METHODS: The risk of SCs was assessed in 1,253 patients diagnosed with HD before the age of 40 years and treated in two Dutch cancer centers between 1966 and 1986. The median follow-up duration was 14.1 years. RESULTS: In all, 137 patients developed SCs, compared with 19.4 cases expected on the basis of incidence rates in the general population (relative risk [RR] = 7.0; 95% confidence interval, 5.9 to 8.3). The 25-year actuarial risk of SC overall was 27.7%. The RR of solid tumors increased greatly with younger age at the first treatment of HD, not only for breast cancer but also for all other solid tumors, with RRs of 4.9, 6.9, and 12.7 for patients first treated at ages 31 to 39 years, 21 to 30 years, and </= 20 years, respectively. Among patients first treated at the age of 20 years or younger, the RR of developing a solid tumor before the age of 40 years was significantly greater than the RR of solid tumor development at ages 40 to 49 years (RR = 27.9 v RR = 4.2; P =.0001). Patients who received salvage chemotherapy had significantly greater risk of solid cancers other than breast cancer than did patients whose treatment was restricted to initial radiotherapy or initial combined-modality treatment (RR = 9.4 and 4.7, respectively; P =. 004). CONCLUSION: After more than 20 years of follow-up, the risk of solid tumors is still much greater in survivors of HD than in the population at large. Reassuringly, the greatly increased risk of solid tumors in patients who were young (</= 20 years of age) at the first treatment seems to decrease as these patients grow older. Our data suggest that chemotherapy may increase the risk of solid tumors from radiotherapy.
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1999
S Senan, J van Sörnsen de Koste, M Samson, H Tankink, P Jansen, P J Nowak, A D Krol, P Schmitz, F J Lagerwaard (1999)  Evaluation of a target contouring protocol for 3D conformal radiotherapy in non-small cell lung cancer.   Radiother Oncol 53: 3. 247-255 Dec  
Abstract: BACKGROUND: A protocol for the contouring of target volumes in lung cancer was implemented. Subsequently, a study was performed in order to determine the intra and inter-clinician variations in contoured volumes. MATERIALS AND METHODS: Six radiation oncologists (RO) contoured the gross tumour volume (GTV) and/or clinical target volume (CTV), and planning target volume (PTV) for three patients with non-small cell lung cancer (NSCLC), on two separate occasions. These were, respectively, a well-circumscribed T1N0M0 lesion, an irregularly shaped T2N0M0 lesion, and a T2N2M0 tumour. Detailed diagnostic radiology reports were provided and contours were entered into a 3D planning system. The target volumes were calculated and beams-eye view (BEV) plots were generated to visualise differences in contouring. A software tool was used to expand the GTV and CTV in three dimensions for an automatically derived PTV. RESULTS: Significant inter-RO variations in contoured target volumes were observed for all patients, and these were greater than intra-RO differences. The ratio of the largest to smallest contoured volume ranged from 1.6 for the GTV in the T1N0 lesion, to 2.0 for the PTV in the T2N2 lesion. The BEV plots revealed significant inter-RO variations in contouring the mediastinal CTV. The PTV's derived using a 3D margin programme were larger than manually contoured PTV's. These variations did not correlate with the experience of ROs. CONCLUSIONS: Despite the use of an institutional contouring protocol, significant interclinician variations persist in contouring target volumes in NSCLC. Additional measures to decrease such variations should be incorporated into clinical trials.
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P C Koper, J C Stroom, W L van Putten, G A Korevaar, B J Heijmen, A Wijnmaalen, P P Jansen, P E Hanssens, C Griep, A D Krol, M J Samson, P C Levendag (1999)  Acute morbidity reduction using 3DCRT for prostate carcinoma: a randomized study.   Int J Radiat Oncol Biol Phys 43: 4. 727-734 Mar  
Abstract: PURPOSE: To study the effects on gastrointestinal and urological acute morbidity, a randomized toxicity study, comparing conventional and three-dimensional conformal radiotherapy (3DCRT) for prostate carcinoma was performed. To reveal possible volume effects, related to the observed toxicity, dose-volume histograms (DVHs) were used. METHODS AND MATERIALS: From June 1994 to March 1996, 266 patients with prostate carcinoma, stage T1-4N0M0 were enrolled in the study. All patients were treated to a dose of 66 Gy (ICRU), using the same planning procedure, treatment technique, linear accelerator, and portal imaging procedure. However, patients in the conventional treatment arm were treated with rectangular, open fields, whereas conformal radiotherapy was performed with conformally shaped fields using a multileaf collimator. All treatment plans were made with a 3D planning system. The planning target volume (PTV) was defined to be the gross target volume (GTV) + 15 mm. Acute toxicity was evaluated using the EORTC/RTOG morbidity scoring system. RESULTS: Patient and tumor characteristics were equally distributed between both study groups. The maximum toxicity was 57% grade 1 and 26% grade 2 gastrointestinal toxicity; 47% grade 1, 17% grade 2, and 2% grade > 2 urological toxicity. Comparing both study arms, a reduction in gastrointestinal toxicity was observed (32% and 19% grade 2 toxicity for conformal and conventional radiotherapy, respectively; p = 0.02). Further analysis revealed a marked reduction in medication for anal symptoms: this accounts for a large part of the statistical difference in gastrointestinal toxicity (18% vs. 14% [p = ns] grade 2 rectum/sigmoid toxicity and 16% vs. 8% [p < 0.0001] grade 2 anal toxicity for conventional and conformal radiotherapy, respectively). A strong correlation between exposure of the anus and anal toxicity was found, which explained the difference in anal toxicity between both study arms. No difference in urological toxicity between both treatment arms was found, despite a relatively large difference in bladder DVHs. CONCLUSIONS: The reduction in gastrointestinal morbidity was mainly accounted for by reduced toxicity for anal symptoms using 3DCRT. The study did not show a statistically significant reduction in acute rectum/sigmoid and bladder toxicity.
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1998
A D Krol, J Hermans, L Dawson, S Snijder, P W Wijermans, H C Kluin-Nelemans, P M Kluin, J H van Krieken, E M Noordijk (1998)  Treatment, patterns of failure, and survival of patients with Stage I nodal and extranodal non-Hodgkin's lymphomas, according to data in the population-based registry of the Comprehensive Cancer Centre West.   Cancer 83: 8. 1612-1619 Oct  
Abstract: BACKGROUND: Primary extranodal lymphomas (EN-NHLs) are a heterogeneous category of tumors that are considered to be different from primary nodal non-Hodgkin's lymphomas (N-NHLs). To what extent these differences have clinical implications is currently not very clear, because knowledge of EN-NHL as a separate group is limited. METHODS: Using data from the Comprehensive Cancer Centre West (CCCW) population-based NHL registry in the Netherlands, N-NHL and EN-NHL patients were compared to determine differences in characteristics at diagnosis, responses to treatment, patterns of failure, and survival. RESULTS: At presentation, EN-NHL patients had poorer performance scores and more often bulky tumors compared with N-NHL patients, resulting in poorer responses to treatment (complete response rates were 72% and 84%, respectively; P=0.04) and inferior 5-year overall survival (49% and 63%, respectively; P=0.003). Among EN-NHL patients, considerable variations in response, survival, and relapse rates were observed, with gastric NHL patients having the best and central nervous system NHL patients having the worst prognosis (66% and 7% 5-year overall survival, respectively). Relapse rates for N-NHL and EN-NHL patients did not differ (39% and 36% 5-year relapse rates, respectively), whereas among EN-NHL patients considerable differences in relapse rates were noted. Relapses among N-NHL patients were mainly found in nodal sites, whereas recurrent disease in EN-NHL patients was mainly found in extranodal sites. CONCLUSIONS: In this population-based study, Stage I EN-NHL patients as a group had a poorer prognosis than N-NHL patients. However, among EN-NHL patients, considerable differences in response, relapse risk, and survival were observed. The failure analysis conducted in this study suggests that patterns of dissemination for N-NHL and EN-NHL are different.
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1997
A D Krol, J Hermans, M H Kramer, P M Kluin, H C Kluin-Nelemans, P Blok, K J Heering, E M Noordijk, J H van Krieken (1997)  Gastric lymphomas compared with lymph node lymphomas in a population-based registry differ in stage distribution and dissemination patterns but not in patient survival.   Cancer 79: 2. 390-397 Jan  
Abstract: BACKGROUND: Non-Hodgkin's lymphoma (NHL) originating in mucosa-associated lymphoid tissue (MALT) is supposed to have different clinical behavior from lymph node NHL. To test this hypothesis, the authors compared data of gastric NHL patients with lymph node NHL patients in a population-based registry for differences in clinical presentation and prognosis. METHODS: Data from 1981-1989 on patients with primary gastric NHL (n = 109) and patients with primary lymph node NHL (n = 658) were retrieved from a Dutch population-based NHL registry. Patients were compared for stage distribution, involved sites, and survival. The prognostic value of grading lymphomas according to the malignancy grades of the Working Formulation for Clinical Usage was compared with the value of grading MALT NHLs as either low grade or high grade malignancies. RESULTS: Patients with gastric NHL presented more often with localized disease. Stage IV patients had a higher rate of dissemination to other non-lymph node sites but less frequent localization in the bone marrow. The restricted pattern of dissemination was reflected in a significantly lower recurrence rate for gastric NHL. Gastric NHL patients had significantly better disease free survival than lymph node NHL patients (80% and 44% at 5 years, respectively; P < 0.001). In contrast, overall survival did not significantly differ between the two groups, and it appeared to depend on disease stage. Grading MALT lymphoma as either low grade (26%) or high grade (70%) malignancies did not provide better prognostic information than grading according to the Working Formulation for Clinical Usage (low 8%, intermediate 75%, high 9%). CONCLUSIONS: Primary gastric NHL shows a restricted dissemination pattern, which gives support to the MALT lymphoma concept. Although this might explain the superior disease free survival observed for gastric NHL patients, it does not translate into better overall survival for these patients.
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1996
M H Kramer, J Hermans, J Parker, A D Krol, J C Kluin-Nelemans, H L Haak, K van Groningen, J H van Krieken, D de Jong, P M Kluin (1996)  Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study.   J Clin Oncol 14: 7. 2131-2138 Jul  
Abstract: PURPOSE: We studied the prognostic significance of bcl2 and p53 protein expression in relation to clinical and pathologic characteristics in patients with diffuse large B-cell lymphoma (LCL). PATIENTS AND METHODS: Three hundred seventy-two patients with LCL were retrieved from a population-based registry for non-Hodgkin's lymphoma (NHL). bcl2 and p53 protein expression was studied on paraffin-embedded tumor tissue by immunohistochemistry in relation to clinical factors. Response to therapy and survival were analyzed in 165 patients who were uniformly staged and treated and for whom all prognostic data were available according to the International Prognostic Index (IPI). RESULTS: Forty-five percent of tumors showed strong expression of the bcl2 protein (bcl2++), with a higher frequency in patients with primary nodal involvement. Disease-free survival (DFS) was significantly better in bcl2-negative/intermediate (bcl2-/+) cases as compared with bcl2++ cases (P = .0011). At 5 years, bcl2-/+ patients showed a DFS rate of 74%, in contrast to bcl2++ patients with a DFS rate of 41% (P = .002). Bcl2 was the strongest independent prognostic value in a multivariate analysis, with a relative risk (RR) of 3.0 in comparison to p53 expression and the clinical factors of the IPI. Overall survival (OS) was not significantly influenced by bcl2 protein expression. p53 protein expression was found in 13% of cases, with a higher frequency in patients with extensive disease. p53 expression did not influence the chance to achieve complete remission (CR) and survival. CONCLUSION: bcl2 protein is frequently expressed in LCL and is a strong independent prognostic factor for DFS. p53 expression is related with high tumor burden, but is not an independent risk factor for CR and survival.
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A D Krol, P Aussems, E M Noordijk, J Hermans, J W Leer (1996)  Local irradiation alone for peripheral stage I lung cancer: could we omit the elective regional nodal irradiation?   Int J Radiat Oncol Biol Phys 34: 2. 297-302 Jan  
Abstract: PURPOSE: The results of local irradiation only for patients with Stage I lung cancer were analyzed to see whether the treatment of regional lymph nodes could be omitted. METHODS AND MATERIALS: One hundred and eight medically inoperable patients with nonsmall cell lung cancer (T1 and peripheral T2) were treated with 60 Gy split course or 65 Gy continuous treatment. The target volume included the primary tumor only, without regional lymph nodes. Response, survival, and patterns of failure were analyzed. RESULTS: The overall response rate was 85% with 50 (46%) complete responses (CRs). Overall survival at 3 and 5 years was 31 and 15%, and cancer-specific survival was 42 and 31% at 3 and 5 years, respectively. The actuarial 5 years local relapse free survival in patients with a CR was 52%. Tumor size (< or = 4 cm) was strongly correlated with the chance of complete remission and better survival. Of patients in complete remission, only two had a regional recurrence as the only site of relapse; an additional two patients had a locoregional recurrence. CONCLUSION: High-dose local radiotherapy on the primary tumor only is justified for medically inoperable patients with peripherally located nonsmall lung cancer. The low regional relapse rate does not support the need for the use of large fields encompassing regional lymph nodes. Using small target volumes, higher doses can be given and better local control rates can be expected.
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1995
J Hermans, A D Krol, K van Groningen, P M Kluin, J C Kluin-Nelemans, M H Kramer, E M Noordijk, F Ong, P W Wijermans (1995)  International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades.   Blood 86: 4. 1460-1463 Aug  
Abstract: An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).
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1990
A D Krol, H J van der Rhee, M Dieleman, K Welvaart (1990)  The 'freckle bus' campaign; an unhealthy phenomenon or a sensible experiment?   Ned Tijdschr Geneeskd 134: 42. 2047-2050 Oct  
Abstract: In the summer of 1989 a screening campaign for skin cancer was organized in four seaside resorts of The Netherlands using a mobile examination room. On 4 consecutive Saturdays 3069 individuals were examined. A total of 65 individuals with a suspected lesion were found. Histological reports were obtained on 46 suspected lesions and showed: 6 melanomas (all with a thickness less than 1 mm), 2 squamous cell carcinomas, 23 basal cell carcinomas, 5 dysplastic naevi and 10 benign skin lesions. The positive predictive value of the clinical examination appeared to be 83%. Much publicity was given to the campaign by the (inter)national media. The effects of this publicity were measured by a questionnaire sent to the general practitioners (856) and dermatologists (25) in the region, of whom 44% and 84%, respectively, responded. It appeared that during and after the campaign there had been an increase in the number of consultations for skin lesions, and an increase in the diagnoses of malignant lesions.
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