Svend Engelholm - Academia.edu (original) (raw)

Papers by Svend Engelholm

Orthopaedic Surgery, Aug 1, 2016

Objective: Improvements in cancer treatment have resulted in an increased number of patients with... more Objective: Improvements in cancer treatment have resulted in an increased number of patients with metastatic spinal cord compression (MSCC). Because patients with MSCC often have a limited expected survival time, maintenance of a high functional level and quality of life are important. However, there is limited information about health-related quality of life (HRQoL) in patients with MSCC. The aim of this study was to examine the feasibility of routine assessment of HRQoL based on the Euroqol-5 dimensions (EQ-5D) questionnaire in a cohort of patients consecutively admitted for evaluation of acute symptoms of MSCC. Methods: From 1 January to 31 December 2011, 544 patients diagnosed with acute symptoms of MSCC were consecutively enrolled in a cohort study. All patients were evaluated through a centralized referral system at one treatment facility. Data were prospectively registered, the variables age, sex, primary oncologic diagnosis, Tokuhashi Revised score, EQ-5D score and treatment modality being recorded on admission. The study patients were treated conservatively with radiotherapy alone or with surgery and subsequent radiotherapy. The EQ-5D questionnaire was administered on admission (baseline) and 6, 12, 26 and 52 weeks after admission. Response rates, completion rates and HRQoL scores were analyzed by relevant subgroups. Response rates were based on all questionnaires returned regardless of whether or not they had been completed, whereas completion rates were based on fully completed questionnaires (i.e., containing responses to all five questions. Results: The mean age was 65 years (range, 20-95 years); 57% of the patients were men. The overall response rate to the Euroqol-5 dimensions (EQ-5D) questionnaires was 84% and the overall completion rate 72%. At baseline, mean EQ-5D scores were significantly lower for patients treated with surgery and subsequent radiotherapy 0.28 (95% CI, 0.19-0.36) than for those treated with radiotherapy alone 0.42 (95% CI, 0.38-0.46). At the one-year follow-up, the mean EQ-5D scores had improved to 0.71 (95% CI, 0.64-0.77) for patients treated with surgery and subsequent radiotherapy and 0.63 (95% CI, 0.56-0.70) for patients treated with radiotherapy alone. Conclusions: Measurement of HRQoL in patients consecutively admitted for evaluation of acute symptoms of MSCC is feasible and detects significant changes over time between treatment modalities and different strata of expected survival.

Spine, Jul 1, 2013

Study Design. A retrospective cohort study of 2321 patients consecutively admitted to one center ... more Study Design. A retrospective cohort study of 2321 patients consecutively admitted to one center and diagnosed with acute symptoms of meta^static spinal cord compression (MSCC). Objective. To assess the possible change in 1-year survival for patients with MSCC from year 2005 through 2010 with respect to the primary cancer diagnosis. Summary of Bacitground Data. An increasing number of patients are offered surgical treatment for MSCC. Among the reasons for this development are high evidence clinical studies, improved surgical techniques, and an increasing number of patients being treated for an oncological condition. Preoperative scoring systems are routinely used in the evaluation of these patients, and the primary oncological diagnosis is an important variable in all these systems. To our knowledge, no studies in a large group of patients have assessed the change in survival in these patients. This is of relevance because such changes in survival could have implications on the scoring systems used In the preoperative evaluation. Methods. All patients referred to the university hospital, Rigshospitalet, suspected of acute symptoms caused by spinal métastases and diagnosed with MSCC from January 1, 2005, to December 31, 2010, were included in a retrospective cohort, n = 2321. For all patients primary tumor, treatment, and 1-year survival was registered. Results. The overall 1-year survival did not change significantly from 2005 to 2010, but there was a significant increase in 1-year survival for the subgroups of patients with lung cancer hazard ratio From the

Radiation Oncology, Feb 4, 2014

Background: Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation... more Background: Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily imageguided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods: A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results: The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion: The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

Gynecologic Oncology, Nov 1, 2012

Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy in... more Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes. Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI. 809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI=200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI). HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.

Radiotherapy and Oncology, May 1, 2017

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PubMed, Sep 21, 1998

Chemotherapy and irradiation it combination or alone have been employed in the treatment of oesop... more Chemotherapy and irradiation it combination or alone have been employed in the treatment of oesophageal carcinomas for many years. However, their place in curative treatment is not definitively clarified. Several non-randomized studies indicate an effect from combined chemotherapy and irradiation possibly followed by surgery. Randomized studies published during the last few years confirm an increased curability in patients who have received combined treatment. New multicentre trials show that a more aggressive attitude is indicated in selected groups of patients with oesophageal carcinoma. Due to the variable spectrum of the disease and complexity of the treatment the treatment should be given in centres which master the different modalities.

Radiotherapy and Oncology, Jul 1, 2019

Introduction: In this study we investigate the risk of radiation-induced serious adverse event of... more Introduction: In this study we investigate the risk of radiation-induced serious adverse event of the spine in a large cohort of consecutive retreated patients with palliative radiotherapy (RT) for metastatic cancer in the spine. Methods and materials: From 2010 to 2014, 2387 patients received spinal irradiation with a palliative intent for metastatic spinal cord compression at our institution. The patients were reviewed for prior RT and 220 patients had received re-irradiation of the spine. Clinical and treatment data were obtained from the patients' records and the RT planning system. Results: Patients had metastatic disease from breast, prostate, lung, hematological or other cancers (22.7%, 21.8%, 21.4%, 3.2% and 30.9%, respectively). Median follow-up was 99 days. Median cumulative EQD2 was 57.6 Gy 2 ; range: 20.0-90.0 Gy. Spinal events related to re-irradiation were observed in fourteen patients; six patients were diagnosed with radiation-induced myelopathy (RIM) and nine patients with radiation-induced vertebral fracture (RIF). In a multivariate analysis, diabetes was related to increased risk of toxicity (HR = 7.9; P = 0.003). Conclusion: The incidence of RIM and RIF (6 and 9 out of 220 patients, respectively) was low in our cohort of re-irradiated patients. Patients with diabetes had a higher risk of adverse events which should be considered before re-irradiation of the spine.

Journal of Clinical Oncology, Feb 10, 2012

153 Background: Returning to work following cancer treatment is a sign of recovery. Side-effects ... more 153 Background: Returning to work following cancer treatment is a sign of recovery. Side-effects might result in sick leave rendering patients unable to work. The purpose of this study was to determine the pattern of sick leave in patients with prostate cancer (PCa) before, during and after definitive radiotherapy. Methods: The Danish DREAM-database contains information on all social benefits paid out to Danish citizens. Based on the DREAM-database it is possible to assess whether a patient is working, on sick leave, or retired. Data on 427 of 473 Danish citizens, treated with definitive intensity-modulated radiotherapy for PCa at our center between January 1 2005 and May 1 2010, were obtained from the DREAM-database. Of the 427 patients 118 patients were working or available to the job market at the start of radiotherapy. Of the 118 patients 59 patients were on sick leave at some point during the course of radiotherapy and they followed in the DREAM-database from one year prior to radiotherapy until one year after the treatment. The median age was 60 (age, range 49–65). Based on the data from the database the 59 patients were divided into the four categories “Working or unemployed”, “Sick leave”, “Retirement” or “Dead”. Furthermore, the patients’ statuses after sick leave were determined. Results: The results are shown in the table. Nearly all patients (91.5%) return to work following sick leave. One year after radiotherapy 64.4% of the patients are working, and 13.6% are on sick leave. Conclusions: The vast majority of patients that are on sick leave during the course of radiotherapy for PCa return to work. However, one year after RT only 64 % are working or available for work indicating that the return to work for a lot of the patients is relatively short-lasting. Further research is needed to clarify why. [Table: see text]

S. Karger AG eBooks, Apr 20, 2015

International Journal of Radiation Oncology Biology Physics, Oct 1, 2011

S. Karger AG eBooks, Apr 16, 2015

Cancer Chemotherapy and Pharmacology, 1990

In a phase II study, 19 patients with previously treated, advanced breast cancer received 50 mg/m... more In a phase II study, 19 patients with previously treated, advanced breast cancer received 50 mg/m2 teniposide (VM-26) i.v. on days 1-5 every 3 weeks. One partial response (PR) (5%) was observed. Toxicity consisting of leukopenia and thrombocytopenia was frequent and severe. VM-26 has minimal therapeutic activity when given at this dose and on this schedule to patients with heavily pretreated metastatic breast cancer.

Scandinavian Journal of Urology and Nephrology, 1984

A case of feminizing Leydig cell tumour is presented. The report includes the results of paraclin... more A case of feminizing Leydig cell tumour is presented. The report includes the results of paraclinical tests performed inter alia to determine whether this rare tumour was benign or malignant.

Investigational New Drugs, Dec 1, 1994

In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed s... more In previous studies, we found that VP-16 (etoposide) induced cytotoxicity and protein-concealed strand break formation was prevented in a small cell lung cancer (SCLC) cell line, when the cells were incubated with aclarubicin prior to treatment with VP-16. In the present work, we studied the effect of adding aclarubicin to the cell suspension after VP-16. In a clonogenic assay, we found that the cytotoxicity induced by VP-16 in SCLC cells was inhibited when cells were postincubated with aclarubicin. The addition of aclarubicin at any time in relation to VP-16 was able to stop further cytotoxicity induced by the topoisomerase II (topo-II) targeting drug. Aclarubicin was also found to antagonize the cytotoxicity induced by VM-26 (teniposide), and m-AMSA. With the alkaline elution technique we found that postincubating the cells with aclarubicin inhibited VP-16-induced DNA strand break formation. In an in vitro system with purified topo-II and naked DNA we likewise found, that postincubation with aclarubicin prevented VP-16 induced cleavage. In the same in vitro system, also baseline cleavage induced by topo-II was inhibited when aclarubicin was present. Importantly, aclarubicin exerted the antagonism to topo-II targeting drugs both when administered prior to and after the topo-II targeting agents. Thus, our data suggest that sequential rather than simultaneous administration of aclarubicin and topo-II targeting agents may be superior with respect to net-cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

International Journal of Radiation Oncology Biology Physics, Oct 1, 1982

The present investigation describes a series of 25 patients with solitary metastasis from a renal... more The present investigation describes a series of 25 patients with solitary metastasis from a renal adenocarcinoma. Forty-eight percent of the patients had metastatic foci in bones, 24% in the lungs, and 28% in a variety of organs. Radiotherapy was the treatment for 64% of the patients, surgery for 36%. Disease control after treatment was obtained in 88% of the patients. The 5-year survival rate was 39%. Sixteen of 25 patients died after a mean survival time of 36 months; 9/25 patients are still living 28-126 months after treatment. Women survived significantly better than men. Patients with normal pre- and post-treatment erythrocyte sedimentation rate (ESR) survived significantly longer than patients with elevated ESR. A definite relationship between ESR and disease activity was demonstrated in 64% of the patients. We concluded that solitary metastases in bones can be treated with radiotherapy; even if 64% of the patients die there is significant clinical remission to be obtained after aggressive treatment. Furthermore, ESR seems to be an important indicator of prognosis and disease activity.

Proteomics Clinical Applications, Nov 29, 2010

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV interna... more To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer (OC) patients. Serum from 150 OC patients was tested using SELDI-TOF-MS. A proteomic prognostic index (xb-pro) was constructed using the regression coefficients based on inter-α trypsin IV internal fragment, B2M and TT. A multivariable Cox survival analysis including the xb-pro index showed that xb-pro (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, HR=2.50, 95% CI: 1.65-3.79), residual tumor after primary surgery (p=0.0005), age (p=0.01) and chemotherapy (p=0.0002) are of independent prognostic value for overall survival. International Federation of Gynecology and Obstetrics stage, performance status, histological type of tumor and serum CA125 were found of no independent value. A proteomic index (xb-pfs) based on B2M and CTAP3 was found to predict progression-free survival (xb-pfs: p=0.008, HR=1.77, 95% CI: 1.17-2.70 together with type of surgery, age and chemotherapy. We found an index with three proteomic biomarkers (xb-pro) to be of independent prognostic value for overall survival and an index with two proteomic biomarkers (xb-pfs) with evidence of independent prognostic value for progression-free survival.

Gynecologic Oncology, Nov 1, 2011

Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, ... more Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim was to determine if these serum proteomic biomarkers alone as well as in combination with age and serum CA125, could be helpful in triage of women with a pelvic mass. We included prospectively 144 patients diagnosed with (OC), 40 with a borderline tumor and 469 with a benign tumor. Surface-enhanced laser desorption/ionization time of flight-mass spectrometry was used for analyses. The Danish Index (DK-Index) based on the proteomic data, age and CA125 was developed using logistic regression models. Multivariate logistic regression analysis demonstrated that the selected proteomic markers, CA125 and age were independent predictors of OC and the combination of these is proposed as the DK-index. A sensitivity (SN) of 99% had a specificity (SP) of 57% for DK-index and 49% for CA125. At a SN of 95%, the SP increased to 81% for DK-index compared to 68% for CA125 alone. For stage I+II the SP was 58% for DK-index and 49% for CA125. For stage III+IV the corresponding values were 94% and 86% respectively. The DK-index warrants further evaluation in independent cohorts.

Acta Oncologica, 2002

A total of 266 recurrence-free breast cancer patients from the randomized DBCG-82TM breast conser... more A total of 266 recurrence-free breast cancer patients from the randomized DBCG-82TM breast conservation trial were called in for a follow-up investigation to study the impact of surgical and radiation treatment factors on the cosmetic and functional outcome after breast conservation. The patients were interviewed and examined after a median follow-up time of 6.6 years, and 194 of them (73%) regarded the cosmetic result as excellent or good. Morbidity assessments showed that breast fibrosis, skin telangiectasia, and breast retraction were significantly associated with a less satisfactory cosmetic result. On univariate analysis, it was found that treatment with a direct anterior electron field produced more morbidity and inferior cosmetic outcomes compared with tangential photon treatment, while increasing breast size was associated with increased breast retraction and breast fibrosis. Treatment characteristics that emerged as independent prognostic factors of a poor cosmetic outcome on multivariate analysis were the use of a direct anterior electron field (OR = 2.15, CI 1.25-3.70) and adjuvant systemic therapy (OR = 2.13, 1.22-3.71). A significant but relatively low level of concordance was found between the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and the clinician&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s evaluations of cosmetic results but self-assessments of breast morbidity and psychological distress were significantly related to the observed treatment-induced side effects after breast-conserving treatment, indicating that subjective perceptions and observations as reported by the patients are relevant for the identification of treatment factors that impact on normal tissue reactions.

This report deals with the preliminary results of trials in the DATECA project with stage I , I1 ... more This report deals with the preliminary results of trials in the DATECA project with stage I , I1 and 111 patients with non-seminomatous germ cell tumours. Stage I patients were randomized between infradiaphragmatic irradiation and observation. No significant difference in recurrence rates has been observed as yet. Eighteen of 95 patients had recurrence with a median time to relapse of 3 months. Fifteen patients achieved complete remission after treatment by combination chemotherapy while 3 patients are still undergoing treatment. Stage I1 patients received 6 series of cis-platinum, bleomycin, and vinblastine. The patients were initially randomized to receive chemotherapy alone versus chemotherapy plus irradiation. Irradiation led to increased toxicity and decreased doses of the antineoplastic drugs. Fiftyone patients were studied. The overall complete remission rate was 89 per cent including 7 patients who achieved complete remission after secondary surgery. Three patients died from testicular tumours and two toxic deaths occurred in this group. Stage 111 patients were treated with 6 series of cisplatinum, bleomycin, and vinblastine. Fifty patients were studied. The complete remission rate was 72 per cent including 2 patients who achieved complete remission after secondary surgery. Sixteen patients relapsed after achieving complete remission with a median time to relapse of 4 months. Eight of these died, 4 achieved a new complete remission, while 4 patients are still under treatment. Sixty per cent of the patients are at present alive without evidence of disease, while 12 patients died from testicular tumours and 2 from toxic side effects.

Journal of Clinical Oncology, Sep 17, 2000

To determine the side effects and feasibility of cisplatin and carboplatin each in combination wi... more To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer. Patients were randomly allocated to receive paclitaxel 175 mg/m(2) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2) or carboplatin (area under the plasma concentration-time curve of 5), both on day 1. The schedule was repeated every 3 weeks for at least six cycles. Women allocated to paclitaxel-cisplatin were admitted to the hospital, whereas the carboplatin regimen was administered to outpatients. A total of 208 eligible patients were randomized. Both regimens could be delivered in an optimal dose and without significant delay. Paclitaxel-carboplatin produced significantly less nausea and vomiting (P: &amp;lt;.01) and less peripheral neurotoxicity (P: =.04) but more granulocytopenia and thrombocytopenia (P: &amp;lt;.01). The overall response rate in 132 patients with measurable disease was 64% (84 of 132 patients), and in patients with elevated CA 125 levels at start, it was 74% (132 of 178 patients). With a median follow-up time of 37 months, the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months. The small number of patients entered onto the study caused wide confidence intervals (CIs) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin (hazards ratio, 1.07; 95% CI, 0.78 to 1.48) and did not allow conclusions about efficacy. Paclitaxel-carboplatin is a feasible regimen for outpatients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin.