Norwegian Radium Hospital Research Articles

BOOK REVIEW

RJ KURMAN, editor. Blaustein's Pathology of the Female Genital Tract. 5th edn. With 1410 Illustrations, 1391 pages. 4060 g. New York, Berlin, Heidelberg: Springer-Verlag, 2002. Hardcover price: EUR 199.00, SFR 322.00, GBP 139.50, USD 189.00 (the Euro price is a net price being subject to local VAT). ISBN 0-387-95203-9. Despite recent strides in ultrasonography and genetics, pathology remains the basic guiding tool in gynecology. Most of our diagnoses are based upon the pathologist's reports, which in turn determine treatment and give the prognostic clues. The clinician who is familiar with the microscopic as well as the macroscopic morphology, will do a better job and be better able to convey the appropriate information to patients. Blaustein's Pathology of the Female Genital Tract is the perfect guide to pathologists and clinicians alike. I reviewed the first edition, which appeared in 1977, for Tidsskrift for Den norske lægeforening (Journal of the Norwegian Medical Association), and was thoroughly impressed. The fifth edition lives up to expectations. The editor, Robert J. Kurman, states that approximately one- third of the book has undergone major revisions, not least because of extensive revisions of the classification systems on tumors and tumor precursors since the fourth edition in 1994. Most of the illustrations are photomicrographs, including 375 new ones. None of them is in color, because Dr Kurman feels that color reproductions generally lack the clarity and crispness of good black-and-white pictures. I agree, and feel confident that all who study this excellent book will too. With one exception (Canada) the 29 authors are from the USA. In lucid chapters, they cover every conceivable aspect of gynecologic pathology, including embryology and disorders of abnormal sexual behavior, diseases of the peritoneum, diseases of the placenta, molecular biology and epidemiology. Endometriosis is extensively covered in the chapter on diseases of the peritoneum. Clinical features and treatment follow the description of almost every pathological entity. Even case reports are included, to illustrate the chronologic sequence of progression of simple endometrial hyperplasia to carcinoma during the course of several years. With new capital letter abbreviations appearing at an 2 amazing rate (AIS, AJCC, APUD, APCCT, ABC, to quote a few from the beginning of the alphabet), a separate list would have been welcome, in addition to appearances in parentheses in the general index. Because of easy access to computerized searches, the lists of references have been limited to articles published in the last decade as well as some large older series that are still clinically relevant. Nevertheless, most of the chapters number upward of 300 references. I note with satisfaction that Scandinavian contributions are included, among them several originating from the Norwegian Radium Hospital. Another reference pleasing to this reviewer is that from the preface: a quotation from Henrik Ibsen in a letter to his publisher, expressing his curious feeling of emptiness upon having finished a play, although it felt good to be done with it. Professor Kurman has every reason to feel good. Blaustein's Pathology of the Female Genital Tract will remain the yardstick for years to come. It belongs in every hospital or departmental library. Individual gynecologists and pathologists will not regret buying it for private perusal.

Scientific misconduct—is there a need for policing the profession

Scientific misconduct—is there a need for policing the profession

Management of high-grade bone sarcomas over two decades: The Norwegian Radium Hospital experience

All cases of high-grade osteosarcoma (OS) (n = 196) and Ewing's sarcoma of bone (ES) (n = 56) treated at the Norwegian Radium Hospital in the period 1980–1999 were analyzed retrospectively. They were allocated to consecutive ten-year periods by their time of diagnosis. Patient and tumour characteristics have been relatively stable. Eighty percent of all patients received surgical treatment and the amputation rate decreased from 64% to 23%. The percentage of patients receiving chemotherapy has remained around 80%. The use of radiotherapy in primary treatment decreased gradually from 33% to 18%. Sarcoma specific survival (SSS) at five years for all patients increased significantly from 39% to 53%. Similar trends for improvement were seen for both OS and ES. In multivariate analysis, independent prognostic factors for improved SSS were non-metastatic disease at diagnosis, age under 40, extremity tumours, small tumours and treatment from 1995 onwards. No major new treatment options have emerged over these 20 years. The improved outcome appears partly to be due to refinements in the use of existing modalities and improved quality and integration of multidisciplinary approaches. Improved formalized organisation of the sarcoma group and annual audited reports of its patient and research activity may also have contributed to improved focus and performance.

Quality of life after total or partial gastrectomy for primary gastric lymphoma

Up to 90% of patients with localized non-Hodgkin's lymphomas (NHL) in the gastrointestinal tract (GI) are cured and decreased use of radical surgery is favoured. Although quality of life (QOL) may impact treatment choice, little is known about QOL in gastric NHL survivors. The self-reported QOL (EORTC QLQ-C30 and a gastric module) and objective findings from upper GI endoscopy were evaluated in patients in complete remission after treatment for primary gastric NHL at the Norwegian Radium Hospital (NRH). Thirty-six (90%) patients completed the questionnaires, 33 (83%) met for endoscopy. Ten patients were treated with total gastrectomy, 17 with partial gastrectomy, while nine patients did not undergo surgery. Gastroscopy was normal in 55% of the non-gastrectomised patients, oesophagoscopy in 69%. Four patients had Barrett's metaplasia. QOL was not different from population values. Patients treated with total gastrectomy reported poorer emotional function, more diarrhoea and more food-related problems (p ≤ 0.05) compared with the others. Based on the higher level of digestive and food related problems after total gastrectomy, stomach-preserving surgery should be preferred whenever possible.

Randomized phase II/III trial of interferon alfa-2a with and without 13- cis-retinoic acid in patients with progressive metastatic renal cell carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951) : Aass N, De Mulder PHM, Mickisch GHJ, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ, Department

Randomized phase II/III trial of interferon alfa-2a with and without 13- cis-retinoic acid in patients with progressive metastatic renal cell carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951) : Aass N, De Mulder PHM, Mickisch GHJ, Mulders P, van Oosterom AT, van Poppel H, Fossa SD, de Prijck L, Sylvester RJ, Department

Quality of life in long-term Hodgkin’s disease survivors with chronic fatigue

The prevalence of chronic fatigue (CF), elevated fatigue levels >six months, is 2.5-3 times higher in long-term Hodgkin disease survivors (HDSs) than in the general population (GP). This is the first study comparing the quality of life (QoL) of chronic fatigued survivors with that of chronic fatigued subjects in the GP. The fatigue questionnaire (FQ) and the SF-36 were mailed to 591 HDSs successfully treated at the Norwegian Radium Hospital from 1971 to 1997. Patient data were compared with nationally representative GP data, adjusted for age, gender and education. The response rate was 80% (N = 475), median follow-up 195 months (range 53-431), mean age 46 years (range 21-74), and 44% were females. HDSs reported significantly poorer QoL than the GP with lower scores on six of eight SF-36 scales (P < 0.001). The subgroup of HDSs with chronic fatigue however (N = 142/475, 30%) had better QoL on five of eight SF-36 scales than subjects with CF in the GP (N = 224/2141, 11%), particularly mental health and emotional role-functioning (P = 0.005 and <0.0001). No differences were found on the physical SF-36 domains. Overall, HDSs reported lower QoL than the GP, in particular the HDSs with CF. Their QoL was similar to that of GP subjects with CF, but with significantly better mental health status. This suggests that CF in long-term survivors may be associated with more physical than psychological aspects of long-term cancer survivorship.

Rearrangement of chromosomal region 8q11–13 in lipomatous tumours: correlation with lipoblastoma morphology

Cytogenetics is of considerable value when diagnosing lipomatous tumours, as different tumour types have different more or less specific chromosomal abnormalities. One such entity is lipoblastoma, which is a benign lipomatous tumour that often exhibits rearrangements of chromosome bands 8q11-13, and the gene PLAG1 has been implicated as the target of these chromosomal changes. All lipomatous tumours karyotyped at the Norwegian Radium Hospital were reviewed, looking for rearrangements of 8q11-13. Five tumours exhibiting chromosomal abnormalities affecting this region were found. Only one of them was morphologically diagnosed as a lipoblastoma, two being classified as lipomas, one as a hibernoma, and one as a well-differentiated liposarcoma. The two tumours successfully analysed with bacterial artificial chromosomes (BACs) covering the gene PLAG1 showed involvement of this gene in the rearrangement. The findings raise the question as to what extent the diagnosis lipoblastoma should be based on histopathological or cytogenetic/molecular data or a combination thereof. When karyotypic information from this series was combined with available literature data, it was found that the sensitivity of 8q11-13 rearrangements for diagnosing lipoblastomas when found in a lipomatous tumour was 77% and that the corresponding specificity was 98%. The validity of these calculations of the diagnostic information provided by the cytogenetic findings is, of course, totally dependent on the morphological diagnosis made in each case. Regardless of what the precise phenotypic diagnosis was, it is suggested that lipomatous tumours with 8q11-13 rearrangement constitute a distinct pathogenetic entity. When selective therapies tailor-made against the specific pathogenetic rearrangement become available, it will become mandatory to pay more attention to the genetic constitution of the tumour cells than to their phenotypic appearance.

Fatigue in Long-Term Hodgkin's Disease Survivors: A Follow-Up Study

To describe total fatigue (TF) and chronic fatigue (CF) in 476 long-term Hodgkin's disease survivors (HDSs). The development in CF over time was explored in 280 of the patients who had also been assessed 8 years earlier. In 2003, the Fatigue Questionnaire was mailed to 610 successfully treated HDSs at the Norwegian Radium Hospital from 1971 to 1997. Mean TF scores and occurrence of CF were compared with general population (GP) values. Four hundred seventy-six complete forms (81%) were received (median age, 46 years; 56% males, median follow-up time, 195 months). There was a positive association between age and TF (P < .05), whereas presence of B symptoms at diagnosis and treatment before 1980 were associated with CF. Mean TF scores were elevated in HDSs compared with the GP (mean TF score, 14.6; 95% CI, 14.1 to 15.7 v 12.1; 95% CI, 11.9 to 12.3, respectively; P < .001), as was the proportion of persons with CF (30% v 11%, respectively; odds ratio = 3.6; P < .001). The 70 patients with CF 8 years earlier still reported higher TF at follow-up than the 210 patients without CF at the previous assessment (mean TF score, 17.0; 95% CI, 15.6 to 18.3 v 13.1; 95% CI, 12.9 to 14.1, respectively; P < .001). Significantly more patients with persisting CF had B symptoms at diagnosis compared with patients who had recovered (P = .05). No significant association with treatment modality and intensity was found. Fatigue remains a major complaint in HDSs several years after treatment, but the association between treatment and fatigue still remains unclear. Many HDSs may recover from CF, particularly patients without B symptoms at diagnosis.

HVps34 Is a Nutrient-regulated Lipid Kinase Required for Activation of p70 S6 Kinase

Mammalian cells respond to nutrient deprivation by inhibiting energy consuming processes, such as proliferation and protein synthesis, and by stimulating catabolic processes, such as autophagy. p70 S6 kinase (S6K1) plays a central role during nutritional regulation of translation. S6K1 is activated by growth factors such as insulin, and by mammalian target of rapamycin (mTOR), which is itself regulated by amino acids. The Class IA phosphatidylinositol (PI) 3-kinase plays a well recognized role in the regulation of S6K1. We now present evidence that the Class III PI 3-kinase, hVps34, also regulates S6K1, and is a critical component of the nutrient sensing apparatus. Overexpression of hVps34 or the associated hVps15 kinase activates S6K1, and insulin stimulation of S6K1 is blocked by microinjection of inhibitory anti-hVps34 antibodies, overexpression of a FYVE domain construct that sequesters the hVps34 product PI3P, or small interfering RNA-mediated knock-down of hVps34. hVps34 is not part of the insulin input to S6K1, as it is not stimulated by insulin, and inhibition of hVps34 has no effect on phosphorylation of Akt or TSC2 in insulin-stimulated cells. However, hVps34 is inhibited by amino acid or glucose starvation, suggesting that it lies on the nutrient-regulated pathway to S6K1. Consistent with this, hVps34 is also inhibited by activation of the AMP-activated kinase, which inhibits mTOR/S6K1 in glucose-starved cells. hVps34 appears to lie upstream of mTOR, as small interfering RNA knock-down of hVps34 inhibits the phosphorylation of another mTOR substrate, eIF4E-binding protein-1 (4EBP1). Our data suggest that hVps34 is a nutrient-regulated lipid kinase that integrates amino acid and glucose inputs to mTOR and S6K1.

Telemedicine in radiotherapy: a study exploring remote treatment planning, supervision and economics

In January 2002, the departments of radiotherapy at the University Hospital of North Norway and the Norwegian Radium Hospital were connected through a 2 Mbit/s digital telecommunication line. The treatment planning systems at the two institutions were connected and videoconferencing units were installed. We explored the feasibility of remote treatment planning, supervision, second opinions and education. Tests involved two dummy cases and six patients. Remote simulation procedures were carried out for five patients. A cost-minimization analysis was performed. Treatment planning was not completely successful as the software could not handle plans including bolus or weighting between the fields. Remote supervision was possible. A common patient record and radiotherapy system, including digital imaging, digital prescription and approval forms and digital signature, were felt to be desirable. The threshold (break-even point) comparing the costs of telemedicine with those of transportation by air was 12 patients/year. Telemedicine in radiotherapy appears to be feasible, but some limitations must be overcome.

Is there an association between haemoglobin, depression, and anxiety in cancer patients?

Objective The aim of this study was to examine the association between haemoglobin levels, anxiety disorder, and depression in cancer patients. Methods Cancer patients attending The Norwegian Radium Hospital (NRH) rated themselves on the Hospital Anxiety and Depression Scale (HADS). Five hundred thirty-two patients also had valid measurements of haemoglobin at the same time. The associations between tertile haemoglobin levels (7.0–12.3 g/dl, 12.4–13.8 g/dl, 13.9–17.1 g/dl) and HADS-defined anxiety disorder and depression were analysed by logistic regression. Results HADS-defined depression was identified in 116 cases (22%) and anxiety disorder in 149 (28%). The haemoglobin levels of the lower and middle tertiles were associated with depression (OR=3.85, 95% CI: 2.06–7.21, and OR=2.45, 95% CI: 1.25–4.81, respectively). Adjustment for covariates did not change the association significantly. No association between haemoglobin and anxiety disorder was found. Conclusion In cancer patients, the risk of depression increases with decreasing haemoglobin levels. This should be taken into account when treatment of anaemic or depressed cancer patients is decided upon.

Guide to Mutation Detection. Edited by Graham R. Taylor and Ian N. Day.

ChemBioChemVolume 6, Issue 6 p. 1130-1130 Book Review Guide to Mutation Detection. Edited by Graham R. Taylor and Ian N. Day. Per O. Ekstrøm, Per O. Ekstrøm Norwegian Radium Hospital, NorwaySearch for more papers by this author Per O. Ekstrøm, Per O. Ekstrøm Norwegian Radium Hospital, NorwaySearch for more papers by this author First published: 30 May 2005 https://doi.org/10.1002/cbic.200500167Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume6, Issue6June 6, 2005Pages 1130-1130 RelatedInformation

Twenty Years Experience with Semen Cryopreservation in Testicular Cancer Patients: Who Needs It?

Purpose: To evaluate the role of semen cryopreservation (SCP) in the fertility saving management of testicular cancer (TC) patients, treated at the Norwegian Radium Hospital between 1983 and 2002. Patients and methods: 422 of 1388 newly diagnosed TC patients had SCP All patients were followed up for post-treatment paternity. Results: During the 20 years study period, by 2002 an increasing percentage of patients had pre-treatment SCP, reaching 43% after 1994. Twenty-nine (7%) of the 422 patients with SCP had used their frozen semen for assisted reproductive techniques (ART) at least once to achieve fatherhood. Pregnancies were achieved in 16 of these patients’ partners, but two of these pregnancies ended in abortions. 67(17%) of 393 men with SCP fathered at least one child without use of frozen semen. The comparable figures for those without SCP were 205 out of 966(21%). Twenty years after orchiectomy the cumulative incidence of first post-treatment fatherhood was 47% for the 393 patients who had SCP but did not use it for ART, and 34% for the 966 patients without SCP ( p = 0.12). Conclusion: If offered, about 50% of the young and middle-aged patients newly diagnosed with TC are interested in pre-treatment SCP. Though our study reveals that a considerable number of TC patients referred to SCP, achieve fatherhood without the use of frozen semen, the psychological impact of pre-treatment cryopreservation is undeniable. Furthermore, for some TC survivors ART with cryopreserved sperm offers the only chance of post-treatment paternity.

Markers of apoptosis in stage IB squamous cervical carcinoma

Aims: To examine the prognostic relevance of the expression of the Bcl-2, Bcl-xL, and Bax proteins in stage IB squamous cervical carcinoma (SCC). Methods: In total, 220 patients who underwent...

The role of radiation treatment in intermediate risk endometrial cancer-pro

The role of adjuvant, post-hysterectomy radiation therapy in patients who have early stage endometrial cancer with high-risk features continues to be a subject of controversy. Findings such as deep myometrial invasion, high grade, large tumor size, lymph-vascular invasion, cervical stromal involvement, and advanced age are all associated with increased risk of locoregional recurrence. Numerous retrospective and several prospective studies have demonstrated that pelvic radiation therapy reduces the risk of recurrence in patients with these findings. However, selection bias makes it impossible to determine the influence of adjuvant treatment from retrospective studies. Several prospective randomized trials have attempted to study the role of adjuvant pelvic radiation in patients with so-called intermediate risk disease. These include recently published trials from PORTEC(1) and the GOG(2) and a much older trial from the Norwegian Radium Hospital(3). Unfortunately, the majority of patients in each of these trials had relatively favorable low-grade or minimally invasive disease. Although all of these trials demonstrated significant reductions in the pelvic recurrence rates with adjuvant radiation, the inclusion of many patients with low-risk disease reduced their power to detect survival differences. Nevertheless, subset analyses suggested that patients who had high intermediate risk factors experienced a benefit from adjuvant radiation therapy with absolute survival differences that could be as great as 15–20% and reductions in the risk of death of as much as 50%. Although it has been suggested that post-hysterectomy pelvic recurrences (most of which involve the vaginal apex) can be easily salvaged, data suggest that 5-year survival rates for patients with vaginal recurrence are ≤40%, particularly for patients with high-grade lesions(4). Intracavity irradiation may reduce the risk of recurrence in the vagina but the Norwegian trial(3) suggests that pelvic RT may be more effective. In the absence of trials adequately addressing the benefit of radiation in patients with high-intermediate risk disease, treatment must be individualized after careful consideration of its potential risks and benefits.

Role of radiation treatment in intermediate risk endometrial cancer-con

Virtually all efforts to define a role for adjuvant therapy in the management of endometrial cancer are confounded by issues relating to adequacy of staging, consistency of pathologic evaluation, agreement on prognostic criteria, and personal investigator bias. Nevertheless, there is general consensus that women in the lowest risk groups are adequately treated by surgery alone, and those in the highest risk subsets who may benefit from additional therapy are ideal candidates for clinical trial participation. Management of the woman with intermediate risk remains controversial. The available data do not support a role for external beam pelvic radiotherapy in such cases. Three large randomized trials have attempted to assess the impact of external beam therapy following hysterectomy for endometrial cancer. The Norwegian Radium Hospital study (1980) randomized 540 clinical stage I patients to receive either pelvic radiation or no therapy after hysterectomy and vaginal cuff brachytherapy. There was no survival difference noted at 5 years (89% vs. 91%) although the radiotherapy group had fewer pelvic failures. The Gynecologic Oncology Group intermediate risk trial reported on 390 evaluable women who received either pelvic irradiation or no therapy after surgery. Progression-free survival was superior in the radiotherapy group because they developed fewer pelvic recurrences. However, overall 4-year survival rates were not statistically different (92% versus 86%). Finally, the PORTEC Study Group randomized 714 intermediate risk patients to either postoperative pelvic radiotherapy or no treatment. Cancer death rates and 5-year survivals were virtually identical (81% versus 85%). Radiated patients had more frequent complications while “no treatment” patients had more pelvic failures. Although it is possible to raise specific objections to some details of methodology in each of these trials, the overall conclusion of each was that no statistically significant survival advantage could be shown for women who received adjuvant pelvic radiotherapy. Consequently, it seems reasonable to recommend a treatment plan that includes hysterectomy alone—or, at most, hysterectomy plus vaginal cuff brachytherapy—as the standard approach for women with intermediate risk tumors.

Hexyl Aminolevulinate

Hexyl aminolevulinate [aminolevulinic acid hexyl ester, hexyl 5-aminolevulinate, 5-ALA hexylester, hexaminolevulinate, Hexvix, Hexvix PD, Hexvix PDT, P 1206] is being developed by PhotoCure, a Norwegian company, for the diagnosis and treatment of bladder cancer. The current standard diagnosis of bladder cancer involves cystoscopic examination of urine and bladder washings and is combined with biopsy for better detection of low-grade malignancies. However, the method largely relies on the experience of the surgeon and often results in false negatives especially for low-grade malignancies and pre-cancerous tissues. Photocure believes that imaging with hexyl aminolevulinate (Hexvix) offers significant advantages over standard diagnostic methods for detection of bladder cancer and also can be used in combination with those to ensure the optimal diagnostic accuracy. PhotoCure's procedure for diagnosis of bladder cancer involves filling of the patient's bladder with hexyl aminolevulinate solution and allowing the active agent to accumulate in the cancerous tissue. Following bladder emptying, blue light illumination is applied to the bladder causing red fluorescence that is clearly visible, thus identifying the cancerous tissue. Imaging with hexyl aminolevulinate improves detection of bladder tumours and also can be used together with transurethral resection to check the completeness of tumour removal. PhotoCure is looking for the opportunity to out-license hexaminolevulinate for all regions except the Nordic regions. PhotoCure has proprietary rights for hexyl aminolevulinate from the Norwegian Radium Hospital. Under the terms of the agreement with the Norwegian Radium Hospital, PhotoCure gains an access to, and an option to acquire, all of the new photodynamic therapy technologies developed by the Norwegian Radium Hospital. For its part, PhotoCure provides research and development funding to the Norwegian Radium Hospital. This 3-year agreement was extended in February 2003 until December 2006. PhotoCure and Karl Storz GmbH of Germany have signed a formal collaboration for the development and marketing of hexyl aminolevulinate (Hexvix) and Karl Storz's D-light system. The two systems will be used in the diagnosis of bladder cancer. PhotoCure and Karl Storz GmbH will jointly apply for a marketing approval of hexyl aminolevulinate (Hexvix) and Karl Storz' D-light system in the US for detection of bladder cancer. The D-light system is already approved in Europe. PhotoCure has also formed a collaborative agreement with the Swiss Federal Institute of Lausanne and the Municipal University Hospital in Lausanne. These institutions have conducted preclinical studies and some exploratory clinical research on the active ingredient of Hexvix in approximately 100 patients. The first MAA for hexyl aminolevulinate fluorescence was filed in Sweden, the reference member state, in December 2002, and was approved in September 2004. PhotoCure plans to launch hexyl aminolevulinate in Sweden in June 2005. Phase II clinical trials were conducted in 52 patients with known or suspected bladder cancer at the university clinics in Switzerland, Germany, Sweden and Norway. Clinical data suggests that hexyl aminolevulinate (Hexvix) is useful in the early diagnosis of bladder cancers allowing treatment to be performed at an earlier stage and, thus, improve the chance of a successful clinical outcome. The company believes that the data from the US phase III programme at 19 leading urology clinics and two multicentre European trials at 28 leading hospitals across nine countries, will sufficiently support an NDA with the US FDA. The US phase III programme with hexyl aminolevulinate was initiated in December 2001. The results from the first European multicentre study conducted in 19 centres in 286 patients confirmed the advantages of hexaminolevulinate fluorescence cystoscopy over standard white light cystoscopy in the detection of bladder cancer. The second multicentre phase III study at ten centres in Germany and the Netherlands in 146 patients with known or suspected bladder cancer was sucessfully completed in March 2003. The independent blind reviewer acknowledged that imaging with hexyl aminolevulinate would result in better treatment options in every fifth patient compared with standard cystoscopy. Hexaminolevulinate is also undergoing early feasibility studies for the diagnosis and treatment of gynaecological and gastrointestinal conditions. PhotoCure was granted a European patent No. 0820432 covering hexyl aminolevulinate, an active ingredient used in Hexvix for the diagnosis and treatment of bladder cancer. The company was also granted patents in Australia, China, the Czech Republic, New Zealand, Russia, Singapore, South Korea and the US.

Protons. A step forward or perhaps only more expensive radiation therapy?

In this issue of Acta Oncologica a series of review papers exploring the possible role of clinical application of protons came to the conclusion that protons may be suitable for 15% of the irradiated Swedish cancer population [1]. Having followed the development in radiation therapy for 30 years, I have reflected a bit on these calculations. Much of the progress in the past history of radiation therapy has been technology driven in the sense that when new machines were developed, giving radiation with new obvious advantages, these were simply used by enthusiasts followed by the other institutions in due time. This can be seen for introduction of high voltage radiation, where for example a Van de Graaff machine was built in 1943 in Bergen against the advice from the leaders at the Norwegian Radium Hospital, an institution that acquired high voltage equipment 10 years later [2]. Similarly there was no formal randomized trial proving that the cobalt unit when first introduced yielded better radiation results than conventional radiation. As far as I know the major promoter for its use was the recommendation from prof. Gilbert Fletcher at MD Anderson Cancer Centre [3]. Also the introduction of conformal radiation in the 1990s was more or less conceptually accepted with only few clinical controlled studies, but a series of model treatment planning studies were published [4]. The modern intensity modulated therapy (IMRT) is widely implemented [5] in most countries based on concepts initially largely developed and published in Acta Oncologica by prof. Anders Brahme [6]. Most major departments are currently investing money in equipment, training and research to implement IMRT for selected patient groups. The future focus has the past years been moved more to the biological properties of the cancer cells, i.e. the accurate localization of the part of a tumour that needs a higher dose and the registration of the actual response to exposure for radiation [7/11]. One may therefore ask whether protons represent a new paradigm shift in radiation oncology, making the efforts to implement IMRT obsolete? The background for the proposal is mainly based on the concept that the radiation can be more precisely enveloped around the target volume (tumour with risk volume) with protons than conventional radiation including IMRT techniques. This is a relevant issue as there seems to be a potential doubling of late secondary cancers due to increased integral doses in areas outside the target when using multiple fields in IMRT [12,13]. Recently a treatment planning study indicated much lower lifetime risk for secondary cancer after proton therapy compared with IMRT, but the risk for IMRT was particularly high in children with medulloblastoma [14]. I could not find any specific publications addressing secondary cancer after proton therapy, despite that 43.000 patents have been exposed to this treatment modality [1]. In the papers better shielding of critical normal tissues surrounding the tumour are frequently stated. This is, however, a statement that should be tested as similar claims were put forward when conformal radiation based on CT-delineation of tumours was introduced. In fact it turned out that treatment volumes had to be increased to encompass the visualized tumour, just as often as they could be reduced. There is therefore a clear limit which cannot be passed with any radiation. A safety margin must prevail. Another concern is the response of normal structures included in the irradiated volume if the sparing

Invasive fungal infections at The Norwegian Radium Hospital 1998–2003

The study evaluates the clinical and microbiological data from patients with documented invasive fungal infections at a comprehensive cancer centre in Norway. Relevant microbiology and pathology databases were screened and medical records were reviewed. 17 yeast infections, including 1 case of cryptococcal meningitis, and no mould infections were found. Diagnostically, in 30% of the positive blood cultures Candida only grew in the Mycosis IC/F bottle. Half of the patients had febrile neutropenia, and 30% had undergone complicated abdominal or pelvic surgery. 12 out of 13 positive blood cultures were Candida albicans. 30% of the patients died of acute septic candidiasis. Within 14 months 90% of the patients were dead from their underlying diseases. A diagnosis of invasive fungal infection is an ominous sign for the patient's overall prognosis.

Pre- and post-treatment daily life function in patients with hormone resistant prostate carcinoma treated with radiotherapy for spinal cord compression

Background and purpose To identify prognostic factors and prospectively evaluate daily life function and pain experience in hormone resistant prostate cancer patients with spinal cord compression treated with radiotherapy. Patients and methods Consecutive patients treated at the Norwegian Radium Hospital from May 1996 to October 1999 participated in the study. Daily life activities were assessed at start and discontinuation of radiotherapy and 2 and 6 months thereafter using a questionnaire based on a slightly modified Barthel activity of daily living Index. The patients were followed to death. Clinical parameters (histology, extent of disease at diagnosis, time from cancer diagnosis to start of radiotherapy, time from neurological symptoms to start of radiotherapy, age, number of spinal lesions, pre-treatment function) were assessed to try to prognosticate post-treatment function. Results Forty-nine patients were evaluable. Time from debut of neurological deficits to start of radiotherapy was median 4 days (range 1–66). Median target dose was 30 Gy (range 9–40). Overall survival from start of radiotherapy was median 3.5 months (range 0.3–36.0). In general, improvement with regard to mobility, daily life activities and sphincter control was reported after irradiation. Post-treatment the majority of patients reported pain, usually intermittent, although they used analgesics. No clinically relevant pre-treatment parameters that predicted function after radiotherapy were identified. Conclusions Radiotherapy may improve mobility, daily life activity and sphincter control in patients with metastatic spinal cord compression due to hormone resistant prostate cancer. Radiotherapy should therefore be considered in all patients irrespective of the neurological deficits.