Eva Cavallin-Ståhl

Publications of Eva Cavallin-Ståhl

• Gene expression profiling indicates that immunohistochemical expression of CD40 is a marker of an inflammatory reaction in the tumor stroma of diffuse large B-cell lymphoma.

  Authors: Karin Rydström, Patrick Joost, Mats Ehinger, Patrik Edén, Mats Jerkeman, Eva Cavallin-Ståhl, Johan Linderoth

  Leukemia & lymphoma. 02/2012;

  Immunohistochemical expression of CD40 is seen in 60-70% of diffuse large B-cell lymphoma (DLBCL) and is associated with a superior prognosis. By using gene expression profiling we aimed to furtherImmunohistochemical expression of CD40 is seen in 60-70% of diffuse large B-cell lymphoma (DLBCL) and is associated with a superior prognosis. By using gene expression profiling we aimed to further explore the underlying mechanisms for this effect. Ninety-eight immunohistochemically defined CD40 positive or negative DLBCL tumors, 63 and 35 respectively, were examined using spotted 55K oligonucleotide arrays. CD40 expressing tumors were characterized by up-regulated expression of genes encoding proteins involved in cell-matrix interactions: collagens, integrin αV, proteoglycans and proteolytic enzymes, and antigen presentation. Immunohistochemistry confirmed that CD40 positive tumors co-express the proinflammatory proteoglycan biglycan (p = 0.005), which in turn correlates with the amount of infiltrating macrophages and CD4 and CD8 positive T-cells. We postulate that immunohistochemical expression of CD40 mainly reflects the inflammatory status in tumors. A high intratumoral inflammatory reaction may correlate with an increased autologous tumor response, and thereby a better prognosis.

• High-dose chemotherapy with autologous stem cell support in patients with metastatic non-seminomatous testicular cancer - a report from the Swedish Norwegian Testicular Cancer Group (SWENOTECA).

  Authors: Hege S Haugnes, Anna Laurell, Ulrika Stierner, Roy M Bremnes, Olav Dahl, Eva Cavallin-Ståhl, Gabriella Cohn-Cedermark

  Acta oncologica (Stockholm, Sweden). 12/2011; 51(2):168-76.

  The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poorThe SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T(½) > 3 days, AFP T(½) > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 × (GFR + 25) mg, cyclofosfamide 6000 mg/m(2) and etoposide 1750 mg/m(2), administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m(2). After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n = 5, 9%). The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous.

• Testicular-cancer survivors experience compromised language following chemotherapy: findings in a Swedish population-based study 3-26 years after treatment.

  Authors: Johanna Skoogh, Gunnar Steineck, Ulrika Stierner, Eva Cavallin-Ståhl, Ulrica Wilderäng, Anders Wallin, Margaret Gatz, Boo Johansson

  Acta oncologica (Stockholm, Sweden). 08/2011; 51(2):185-97.

  Studies suggest an increased risk for compromised cognitive function among cancer survivors. It is unclear to what extent chemotherapy is the cause and how the dysfunction, when present, affectsStudies suggest an increased risk for compromised cognitive function among cancer survivors. It is unclear to what extent chemotherapy is the cause and how the dysfunction, when present, affects everyday life. The objective was to study self-reported behaviours that may depend on cognitive function, among testicular-cancer survivors who received various cycles of cisplatin-based chemotherapy by comparing them with those who did not. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programs SWENOTECA I-IV between 1981 and 2004. During an 18-month qualitative phase we constructed a study-specific questionnaire including questions about specific activities and behaviour in everyday life. We obtained information from 960 of 1173 (82%) testicular-cancer survivors diagnosed on average 11 years previously. The prevalence of "saying similar but incorrect words" at least once a week was 5% among those having received no chemotherapy versus 16% among those having received five or more cycles, giving a prevalence ratio ("relative risk", RR) of 3.3 with a 95% confidence interval of 1.5 to 7.1. The corresponding figure for "saying words in the wrong order" was 3.1 (1.7-5.8), for "difficulties understanding what other people mean" 3.1 (1.3-7.7), for "saying words other than planned" 2.2 (1.1-4.5) and for "difficulties completing sentences" 2.0 (1.0-3.6). The relative risks for those with a low level of education ranged between 4.9 (1.6-14.9) and 15.3 (1.9-120.5). Testicular-cancer survivors in Sweden who have received five or more cycles of cisplatin-based chemotherapy experience an increased incidence of long-term compromised language; the effect is primarily seen among men with a low level of education.

• Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: a report from the Swedish-Norwegian Testicular Cancer Group.

  Authors: Sven-Erik Olofsson, Torgrim Tandstad, Mats Jerkeman, Olav Dahl, Olof Ståhl, Olbjørn Klepp, Roy M Bremnes, Gabriella Cohn-Cedermark, Carl W Langberg, Anna Laurell, Arne Solberg, Ulrika Stierner, Rolf Wahlqvist, Hans Wijkström, Harald Anderson, Eva Cavallin-Ståhl

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 05/2011; 29(15):2032-9.

  From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strictFrom 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for β-human chorionic gonadotropin (β-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.

• Estrogen receptor α single nucleotide polymorphism modifies the risk of azoospermia in childhood cancer survivors.

  Authors: Patrik Romerius, Aleksander Giwercman, Christian Moëll, Thomas Relander, Eva Cavallin-Ståhl, Thomas Wiebe, Christer Halldén, Yvonne Lundberg Giwercman

  Pharmacogenetics and genomics. 03/2011; 21(5):263-9.

  Cancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatmentCancer treatment in childhood leads to permanent azoospermia in a significant number of boys and those who are diagnosed with cancer before puberty do not have the option of pretreatment cryopreservation of spermatozoa. However, there is an interindividual variation in the sensitivity to gonadotoxic effects of cancer therapy, which probably is due to genetic factors. Identification of genetic markers for the risk of azoospermia in childhood cancer survivors may help in identifying boys to whom testicular cryopreservation should be offered. Fifty-one single nucleotide polymorphisms (SNPs) being markers of 12 different haplotype blocks in the androgen receptor, estrogen receptor (ER) α and ER β genes were examined in 127 adult childhood cancer survivors. In ERα, markers of one specific haplotype block (rs2207396, rs9340958, rs9340978) were associated with an increased risk of azoospermia. Compared with those with the GG genotype, patients being heterozygous for the A allele in rs2207396 had a significantly increased risk of azoospermia [odds ratio (OR): 3.8; 95% confidence interval: 1.5-9.5; P=0.008], this OR being even higher in the subgroup treated with alkylating drugs (OR: 8.8; 95% confidence interval: 2.1-36; P=0.004). In this subgroup, 48% of the patients carried the A allele of rs2207396, this proportion being 70% among the azoospermic patients. Use of genetic markers of high risk of posttreatment azoospermia may, in the future, prove an important clinical tool in selection of boys to whom preservation of testicular tissue before cancer therapy should be offered.

• Risk of birth abnormalities in the offspring of men with a history of cancer: a cohort study using Danish and Swedish national registries.

  Authors: Olof Ståhl, Heather A Boyd, Aleksander Giwercman, Morten Lindholm, Allan Jensen, Susanne Krüger Kjær, Harald Anderson, Eva Cavallin-Ståhl, Lars Rylander

  Journal of the National Cancer Institute. 02/2011; 103(5):398-406.

  The potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. We identified all singletonThe potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring. We identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1,777,765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1,769,095 children without a paternal history of cancer, 25,926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided. The offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, P(interaction) = .84). We observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.

• Sperm DNA integrity in men treated for childhood cancer.

  Authors: Patrik Romerius, Olof Ståhl, Christian Moëll, Thomas Relander, Eva Cavallin-Ståhl, Helen Gustafsson, Kerstin Löfvander Thapper, Katarina Jepson, Marcello Spanò, Thomas Wiebe, Yvonne Lundberg Giwercman, Aleksander Giwercman

  Clinical cancer research : an official journal of the American Association for Cancer Research. 08/2010; 16(15):3843-50.

  It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this studyIt is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account. In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay. In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), -0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6-10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083-5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1-4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3-18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given. DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring.

• Hypogonadism Risk in Men Treated for Childhood Cancer.

  Authors: Patrik Romerius, Olof Ståhl, Christian Moëll, Thomas Relander, Eva Cavallin-Ståhl, Thomas Wiebe, Yvonne Lundberg Giwercman, Aleksander Giwercman

  The Journal of clinical endocrinology and metabolism. 09/2009;

  Context: Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. Objective: The aim ofContext: Pediatric cancer treatment may imply an increased risk of hypogonadism, leading to metabolic disorders and osteoporosis. Such complications are potentially preventable. Objective: The aim of this study was to assess diagnosis- and treatment-dependent risk of hypogonadism in male childhood cancer survivors (CCS). Design: Male CCS who were treated during the period 1970-2002 and who in 2004 were 18-45 yr of age were eligible. Setting: The study was conducted in a university hospital clinic. Patients: A consecutive group of CCS treated at Lund University Hospital was selected for the study, of whom 151 (38%) agreed to participate. Furthermore, 141 healthy fertile men served as controls. Interventions: We measured serum levels of free and total testosterone, SHBG, and LH. Main Outcome Measures: Odds ratios (OR) for biochemical hypogonadism, defined as total testosterone less than 10 nmol/liter and/or LH above 10 IU/liter, were calculated and related to type of cancer, treatment received, as well as testicular volume. Results: Hypogonadism was more commonly detected in CCS than in controls (OR, 6.7; 95% CI, 2.7, 17). The increased presence of hypogonadism was noted in the following treatment groups: brain surgery, chemotherapy (with and without radiotherapy), and testicular irradiation. Low total testicular volume (</=24 ml) was associated with a high risk of hypogonadism (OR, 31; 95% CI, 11, 92). Conclusion: Adult male survivors of childhood cancer are at risk of hypogonadism, which should be acknowledged in the long-term follow-up of these men.

• Emotional disorders in testicular cancer survivors in relation to hypogonadism, androgen receptor polymorphism and treatment modality.

  Authors: Jakob Eberhard, Olof Ståhl, Gabriella Cohn-Cedermark, Eva Cavallin-Ståhl, Yvonne Giwercman, Hamideh Rastkhani, Lars Rylander, Malin Eberhard-Gran, Ulrik Kvist, Aleksander Giwercman

  Journal of affective disorders. 08/2009;

  PURPOSE: It has been documented that testicular germ cell cancer (TGCC) patients may be at increased risk of developing emotional distress (EMD). Hence, the aim of the present study was toPURPOSE: It has been documented that testicular germ cell cancer (TGCC) patients may be at increased risk of developing emotional distress (EMD). Hence, the aim of the present study was to investigate whether EMD is related to the presence of hypogonadism, androgen receptor (AR) polymorphism and/or treatment intensity. PATIENTS AND METHODS: Three to five years after treatment, testosterone and luteinizing hormone (LH) levels were measured in 165 TGCC patients. These patients also completed a questionnaire concerning mental health. EMD was measured by the Hospital Anxiety and Depression Scale (HADS). The androgen receptor (AR) gene has two polymorphic regions in exon I; glutamine encoding CAG and glycine encoding GGN repeats. Association between emotional disorders and AR polymorphisms as well as type of treatment was assessed. RESULTS: Neither anxiety (OR 1.0; 95% CI 0.40-2.4) nor depression (OR 1.1; 95% CI 0.20-6.4) were overrepresented in biochemically hypogonadal TGCC patients and no association between AR polymorphisms and EMD was found. Patients treated with >/=5 cycles of cisplatinum based chemotherapy due to refractory or relapsed disease were more prone to experiencing symptoms of anxiety (p=0.006), but not depression (p=0.38). CONCLUSIONS: Biochemical hypogonadism and AR polymorphism do not seem to be risk factors for EMD in TGCC patients. Patients with refractory or relapsed disease receiving >/=5 cycles of cisplatinum based chemotherapy may, to a higher degree than patients receiving less intense therapy, suffer from anxiety.

• Sexual Function in Men Treated for Testicular Cancer.

  Authors: Jakob Eberhard, Olof Ståhl, Gabriella Cohn-Cedermark, Eva Cavallin-Ståhl, Yvonne Giwercman, Lars Rylander, Malin Eberhard-Gran, Ulrik Kvist, Kerstin S Fugl-Meyer, Aleksander Giwercman

  The journal of sexual medicine. 05/2009;

  ABSTRACT Introduction. Testicular germ cell cancer (TGCC) patients may be at risk of developing sexual dysfunction after treatment. Aim. The aim of this study was to assess the prevalence of sexualABSTRACT Introduction. Testicular germ cell cancer (TGCC) patients may be at risk of developing sexual dysfunction after treatment. Aim. The aim of this study was to assess the prevalence of sexual dysfunctions in TGCC patients 3 to 5 years after treatment, and relate findings to biochemical hypogonadism, treatment intensity, and the expected prevalence in the Swedish male population. Methods. A questionnaire study on 129 consecutive TGCC patients 3 to 5 years post-treatment was performed. Comparators were an age-matched nationally representative group of men (N = 916) included in a study on sexual life in Sweden. Main Outcome Measures. Sexual functions (including erectile dysfunctional distress), time since last intercourse, sexual satisfaction, and experience of sexological treatment seeking were assessed using the same questions used in the epidemiological study on sexual life in Sweden. The findings in TGCC patients were correlated to biochemical signs of hypogonadism and type of oncological treatment: Surveillance, adjuvant chemotherapy, adjuvant radiotherapy, or standard doses of chemotherapy. Results. A higher proportion of TGCC patients than comparators were likely to report low sexual desire (odds ratio [OR] 6.7 [95% confidence interval {CI} 2.1-21]) as well as erectile dysfunction (OR 3.8 [95% CI 1.4-10]). No significant differences were observed regarding erectile dysfunctional distress, change of desire over time, interest in sex, premature or delayed ejaculation, time since last intercourse, need for or receiving sexual advice, or sexual satisfaction. Hypogonadism did not predict erectile dysfunction (OR 1.1 [95% CI 0.26-4.5]) or low sexual desire (OR 1.2 [95% CI 0.11-14]). Treatment modality had no obvious impact on sexual function. Conclusion. Men treated for testicular cancer had higher risk of having low sexual desire and erectile dysfunction 3 to 5 years after completion of therapy than comparators. These sexual dysfunctions were not significantly associated with treatment intensity or hypogonadism. Eberhard J, Ståhl O, Cohn-Cedermark G, Cavallin-Ståhl E, Giwercman Y, Rylander L, Eberhard-Gran M, Kvist U, Fugl-Meyer KS, and Giwercman A. Sexual function in men treated for testicular cancer. J Sex Med **;**:**-**.

• Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma.

  Authors: Johan Linderoth, Patrik Edén, Mats Ehinger, Jeanette Valcich, Mats Jerkeman, Pär-Ola Bendahl, Mattias Berglund, Gunilla Enblad, Martin Erlanson, Göran Roos, Eva Cavallin-Ståhl

  British journal of haematology. 06/2008; 141(4):423-32.

  In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stageIn order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.

• A subset of CD5- diffuse large B-cell lymphomas expresses nuclear cyclin D1 with aberrations at the CCND1 locus.

  Authors: Mats Ehinger, Johan Linderoth, Birger Christensson, Birgitta Sander, Eva Cavallin-Ståhl

  American journal of clinical pathology. 05/2008; 129(4):630-8.

  In 231 diffuse large B-cell lymphomas, the expression of cyclin D1 and CD5 was evaluated. All cases were CD5-. Ten (4.3%) were positive for cyclin D1 and were subjected to fluorescence in situIn 231 diffuse large B-cell lymphomas, the expression of cyclin D1 and CD5 was evaluated. All cases were CD5-. Ten (4.3%) were positive for cyclin D1 and were subjected to fluorescence in situ hybridization at the CCND1 locus. One case showed the t(11;14). In another case, the telomeric probe signal for cyclin D1 was lost in most tumor cells, and in a small proportion of the cells, there were fluorescence signals indicative of the t(11;14). Two other cases displayed additional cyclin D1 signals in the absence of the t(11;14). All cases but 1 were positive for bcl-6 or MUM1, disfavoring the possibility of misdiagnosed blastoid variants of CD5- mantle cell lymphomas. Thus, contrary to the current view, there seems to exist a certain number of cyclin D1+ and CD5- diffuse large B-cell lymphomas, some of which have structural aberrations at the CCND1 locus, including the t(11;14).

• Risk factors for post-treatment hypogonadism in testicular cancer patients.

  Authors: Jakob Eberhard, Olof Ståhl, Magdalena Cwikiel, Eva Cavallin-Ståhl, Yvonne Giwercman, Eva Cecilia Salmonson, Aleksander Giwercman

  European journal of endocrinology / European Federation of Endocrine Societies. 05/2008; 158(4):561-70.

  OBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (afterOBJECTIVES: Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined. METHODS: Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)). RESULTS: HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460). CONCLUSIONS: It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH.

• European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

  Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl [......] Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase

  European urology. 04/2008; 53(3):497-513.

  OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world.OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

• European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

  Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl [......] Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase

  European urology. 04/2008; 53(3):478-96.

  OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. InOBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. METHODS: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

• CD40 expression identifies a prognostically favourable subgroup of diffuse large B-cell lymphoma.

  Authors: Johan Linderoth, Mats Ehinger, Mats Jerkeman, Pär-Ola Bendahl, Måns Akerman, Mattias Berglund, Gunilla Enblad, Martin Erlanson, Göran Roos, Eva Cavallin-Ståhl

  Leukemia & lymphoma. 10/2007; 48(9):1774-9.

  In order to confirm our earlier findings of the prognostic effects of CD23 and CD40 expression in diffuse large B-cell lymphoma (DLBCL), possibly due to association with the germinal center (GC)In order to confirm our earlier findings of the prognostic effects of CD23 and CD40 expression in diffuse large B-cell lymphoma (DLBCL), possibly due to association with the germinal center (GC) phenotype and/or an increased autologous tumour response, tumour specimens from 125 patients with de novo DLBCL were investigated for immunohistochemical expression of CD23, CD40, BCL6, CD10, MUM1, CD4 and CD8. CD40 was positive in 64% and was associated with improved overall survival (p = 0.03). A GC phenotype was present in 47%, and was also associated with a better overall survival (p = 0.006) but did not correlate with CD40-expression. There was no correlation between amount of tumour infiltrating T-cells and CD40-positivity. CD23 was positive in 10% and expression did not correlate with prognosis. In conclusion, the prognostic effect of CD40 expression was confirmed, but did not correlate with GC-phenotype or T-cell infiltration.

• Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma.

  Authors: Johan Linderoth, Mats Ehinger, Måns Akerman, Eva Cavallin-Ståhl, Gunilla Enblad, Martin Erlanson, Mats Jerkeman

  European journal of haematology. 09/2007; 79(2):146-9.

  OBJECTIVE: In this study, our aim was to investigate how different immunohistochemical techniques may influence the result of BCL6 positivity and categorization in germinal center (GC) and non-GCOBJECTIVE: In this study, our aim was to investigate how different immunohistochemical techniques may influence the result of BCL6 positivity and categorization in germinal center (GC) and non-GC derived diffuse large B-cell lymphoma (DLBCL), as it has been proposed that classification of DLBCL according to cell-of-origin by immunohistochemistry may be performed as a routine procedure in the diagnostic work-up. However, a number of technical issues need to be solved before introducing this as a standard technique. METHODS: Tumor specimens from 122 patients with de novo stage II-IV disease, adequately treated with anthracycline-containing chemotherapy regimens were collected. Immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4 was examined using a tissue microarray (TMA) technique. BCL6 and CD10 were also evaluated on whole tissue sections. RESULTS: Due to profound tissue heterogeneity, BCL6 showed a wide range of positivity, with a high number of false negative results by TMA (25% positive), compared to 53% on whole tissue sections (WTS). CD10 was more homogeneously expressed, and TMA results corresponded better to WTS. Consequently, the results from categorization into GC and non-GC DLBCL differed considerably by use of the two methods, and resulted in very different outcome in terms of overall survival. CONCLUSION: Immunohistochemical GC-status determined on TMA is not reliable enough to be used for individual treatment decisions in DLBCL, mostly due to difficulties in interpreting BCL6 status.

• Adult survivors of childhood acute lymphoblastic leukaemia with GH deficiency have normal self-rated quality of life but impaired neuropsychological performance 20 years after cranial irradiation.

  Authors: Katarina Link, Christian Moëll, Kai Osterberg, Roger Persson, Palle Ørbaek, Stanislaw Garwicz, Eva Cavallin-Ståhl, Eva Marie Erfurth

  Clinical endocrinology. 12/2006; 65(5):617-25.

  OBJECTIVE: Cranial radiotherapy (CRT) was, until recently, important for achieving long-term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, theOBJECTIVE: Cranial radiotherapy (CRT) was, until recently, important for achieving long-term survival in acute lymphoblastic leukaemia (ALL). Because survival rates have improved markedly, the long-term complications, such as GH deficiency (GHD) and neuropsychological impairment, have become increasingly important. DESIGN AND PATIENTS: The level of self-reported quality of life and neuropsychological functioning was investigated in 44 adults (21 women) with a median age of 25 years who had been treated for childhood onset (CO) ALL with CRT (median 24 Gy). Comparison was made with matched population controls. A subset of patients with GHD was evaluated for neuropsychological functioning after 1 year of GH treatment. RESULTS: Compared to controls, the patients had significantly lower performance in neuropsychological tests. Early age at treatment had a significant negative impact on neuropsychological performance in adulthood. No relationship was found between dose of CRT, time since treatment of ALL or gender and neuropsychological performance. Compared to controls, the patients did not show a poor quality of life or a lowered availability of social interactions or social networks; however, significantly more patients were living alone or with their parents. After GH testing, the patients were all considered GH deficient or insufficient, but no relationship was observed between stimulated peak GH secretion and neuropsychological performance. Treatment with GH for 1 year in a subgroup of the patients did not improve their neuropsychological performance. CONCLUSIONS: This study showed that adults treated with CRT for CO ALL had GHD and significantly impaired neuropsychological performance, although self-reported quality of life was not affected. The effect of GH treatment in this patient group has to be further elucidated.

• A novel platform for radioimmunotherapy: extracorporeal depletion of biotinylated and 90Y-labeled rituximab in patients with refractory B-cell lymphoma.

  Authors: Ola Lindén, Jan Kurkus, Michael Garkavij, Eva Cavallin-Ståhl, Michael Ljungberg, Rune Nilsson, Tomas Ohlsson, Bengt Sandberg, Sven-Erik Strand, Jan Tennvall

  Cancer biotherapy & radiopharmaceuticals. 09/2005; 20(4):457-66.

  Radioimmunotherapy is limited by the absorbed dose to radiosensitive organs. Removal of circulating radiolabeled MAbs after tumor tissue has been optimally targeted and should permit theRadioimmunotherapy is limited by the absorbed dose to radiosensitive organs. Removal of circulating radiolabeled MAbs after tumor tissue has been optimally targeted and should permit the administration of higher radioactivity to patients, resulting in a higher absorbed tumor dose. A novel "extracorporeal affinity adsorption treatment" (ECAT) device (MitraDep)was tested, with which biotinylated and radiolabeled MAbs can be removed from the circulation by passing whole blood over a filter coated with avidin. The antibodies were simultaneously radiolabeled and biotinylated using a trifunctional moiety comprising DOTA and biotin. Eight patients--all but 1 of whom with aggressive or mantle cell B-cell lymphoma-- who had failed to respond to standard therapies received infusions of 250 mg/m(2) cold rituximab and 150 MBq (111)In-rituximab-biotin for immunoscintigraphy. A week later, the patients were treated with another 250 mg/m(2) rituximab followed by (111)In/-(90)Y-rituximab-biotin (11 or 15 (90)Y MBq/kg). ECAT was performed 48 hours later. All 8 patients receiving (111)In-rituximab-biotin showed tumor uptake. Seven patients received radioimmunotherapy and subsequent ECAT. The mean depletion of (90)Y-rituximab-biotin in whole blood after ECAT was 96%, in the whole body 49%, in the lungs 62%, and in the liver and kidneys 40%. No effects on patients' vital signs and no adverse effects on hematological or coagulation parameters was observed during the ECAT procedure. A dose-escalation study is initiated.

• Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis.

  Authors: Mattias Berglund, Ulf Thunberg, Rose-Marie Amini, Majlis Book, Göran Roos, Martin Erlanson, Johan Linderoth, Michael Dictor, Mats Jerkeman, Eva Cavallin-Ståhl, Christer Sundström, Suzanne Rehn-Eriksson, Carin Backlin, Hans Hagberg, Richard Rosenquist, Gunilla Enblad

  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 09/2005; 18(8):1113-20.

  Diffuse large B-cell lymphoma (DLBCL) has been shown to be comprised of at least two prognostic entities, depending on its resemblance to normal germinal center or activated B cells, using globalDiffuse large B-cell lymphoma (DLBCL) has been shown to be comprised of at least two prognostic entities, depending on its resemblance to normal germinal center or activated B cells, using global gene expression profiling. Also, the expression patterns of bcl-6, CD10 and IRF-4 (also known as MUM1) have been suggested as alternative means of identifying the germinal- and nongerminal center (activated B-cell like) groups. In the present study, we evaluated by immunohistochemistry the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 in a large material of 161 DLBCL patients. Using two different approaches, patients with germinal center phenotype displayed a significantly better survival than the nongerminal center group. Positive staining for bcl-6 or CD10 predicted for superior survival, while expression of IRF-4 alone showed no association with prognosis. Furthermore, expression of bcl-2 was associated with worse event-free survival and overall survival. In a multivariate analysis, a high international prognostic index score (3-5), non-GC phenotype and bcl-2 were independent adverse prognostic factors. Here we confirm the prognostic importance of determining the germinal- or nongerminal center phenotype in patients with DLBCL.