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Background. During the last decades the diagnosis, treatment, and prognosis of breast cancer have changed and improved in Denmark. The first mammography screening programme started in 1991. However, for many years only about 20% of Danish women aged 50–69 were offered screening. The national roll-out of screening took place in 2008–2010. Material and methods. Based on published Danish data, this overview describes the status of diagnosis and treatment, and the screening programme. For further evaluating the potential overdiagnosis and overtreatment, additional Danish Breast Cancer Cooperative Group (DBCG) data are included. Results and conclusion. Using incidence-based mortality method, reduction in breast cancer mortality was estimated to be 25% in the target group of women after 10 years of screening in Copenhagen; an outcome comparable to that of randomised controlled trials. A recent Danish study has indicated overdiagnosis to be around 4%. Others have estimated overdiagnosis to be 33%. National DBCG data showed that the rude breast cancer incidence increased during the period 1990–2011 from 126 to 206 per 100 000. The incidence was almost constant for women younger than 50 years. In regions not offering screening, the incidence increased with 3% per year for women aged 50–69 years with similar trends for small and large tumours. After introduction of screening the increase in the age group 50–69 years was confined to small tumours ≤ 20 mm, and most pronounced for node negative patients. From the 1990s, the use of breast conserving surgery has increased from around 25% to 69% in 2010. Screening has not increased the number of mastectomies. Breast cancer treatment in Denmark is evidence based and in agreement with international recommendations. After the introduction of mammography screening the absolute number of patients with a more advanced stage at diagnosis and the absolute number of patients undergoing mastectomy have decreased.

The effectiveness of abdominal compression for motion management in hepatobiliary-pancreatic (HPB) radiotherapy has not been systematically evaluated.A systematic review was carried out using PubMed/Medline, Cochrane Library, Web of Science, and CINAHL databases up to 1 July 2021. No date restrictions were applied. Additional searches were carried out using the University of Manchester digital library, Google Scholar and of retrieved papers' reference lists. Studies conducted evaluating respiratory motion utilising imaging with and without abdominal compression in the same patients available in English were included. Studies conducted in healthy volunteers or majority non-HPB sites, not providing descriptive motion statistics or patient characteristics before and after compression in the same patients or published without peer-review were excluded. A narrative synthesis was employed by tabulating retrieved studies and organising chronologically by abdominal compression device type to help identify patterns in the evidence.The inclusion criteria were met by 6 studies with a total of 152 patients. Designs were a mix of retrospective and prospective quantitative designs with chronological, non-randomised recruitment. Abdominal compression reduced craniocaudal respiratory motion in the majority of patients, although in four studies there were increases seen in at least one direction. The influence of patient comorbidities on effectiveness of compression, and/or comfort with compression was not evaluated in any study.Abdominal compression may not be appropriate for all patients, and benefit should be weighed with potential increase in motion or discomfort in patients with small initial motion (5 mm). Patient factors including male sex, and high body mass index (BMI) were found to impact the effectiveness of compression, however with limited evidence. High-quality studies are warranted to fully assess the clinical impact of abdominal compression on treatment outcomes and toxicity prospective in comparison to other motion management strategies.

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

By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D0/N were used, only in 2D was used. In 21 papers the D0/N values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of 'low-dose-region-parameters' is reviewed.

This paper presents an insight into the critical discussions and the current strategies of the Nordic countries for handling the variable proton relative biological effectiveness (RBE) as presented at The Nordic Collaborative Workshop for Particle Therapy that took place at the Skandion Clinic on 14th and 15th of November 2019.In the current clinical practice at the two proton centres in operation at the date, Skandion Clinic, and the Danish Centre for Particle Therapy, a constant proton RBE of 1.1 is applied. The potentially increased effectiveness at the end of the particle range is however considered at the stage of treatment planning at both places based on empirical observations and knowledge. More elaborated strategies to evaluate the plans and mitigate the problem are intensely investigated internationally as well at the two centres. They involve the calculation of the dose-averaged linear energy transfer (LETMethods and tools for LETThe need for collaboration between the clinical proton centres in establishing common platforms and perspectives for treatment planning evaluation and optimisation is highlighted as well as the need of close interaction with the research academic groups that could offer a complementary perspective and actively help developing methods and tools for clinical implementation of the more complex metrics for considering the variable effectiveness of the proton beams.

In the Nordic countries, as in the rest of the world, particle therapy as a radiotherapy modality, is evolving, albeit the hard evidence for the clinical benefit still is scarce. However, a common goal for the Nordic countries is to include a minimum of 80% of the patients treated with particle therapy into clinical trials. In this paper, we summarize the current status of clinical trials involving particle therapy in the Nordic countries, with an overview of both active and coming trials. So far, one is closed for inclusion and data are being analyzed, seven trials are actively recruiting patients and several more trials are underway. No common Nordic trial has yet been designed, nor is in the planning phase, and the authors will discuss the obstacles as well as the opportunities a common Nordic platform may represent.

BACKGROUND: Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment. Neuroimaging evidence has begun to elucidate the neurobiological underpinnings of cancer-related cognitive impairment. The aim of this paper was to systematically review available literature on structural brain alterations following adult non-central nervous system (CNS) cancers and associated treatments.METHODS: This review followed PRISMA guidelines and was registered in PROSPERO (ID#107387). Comprehensive searches were conducted in June 2018 using PubMed and Web of Science. Inclusion criteria were English peer-reviewed journal articles of formal, controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors. Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.RESULTS: Thirty-six publications of prospective and cross-sectional studies met inclusion criteria and were included. Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidenced by reduced global and local gray matter volumes, impaired white matter microstructural integrity, and brain network alterations. Structural alterations were most often evident when cancer-treated groups were compared with healthy controls, and more subtle when compared with cancer controls. Regarding the existence of pretreatment impairments, the evidence was equivocal. There was significant between-study heterogeneity in imaging analytical approaches and use of statistical adjustments. Over half reported associations with cognitive outcomes, though regions and associated cognitive domains were heterogeneous.CONCLUSIONS: Structural brain alterations following cancer and cancer treatments were reported in a majority of the reviewed studies. However, the extent of observed alterations depended on the choice of comparison groups. Methodological issues exist that will need to be addressed systematically to ensure the validity of findings. Large-scale prospective studies with extended assessment points are warranted to replicate and build upon initial findings.

A requirement for having a research paper published in many medical journals is that the authors include a data sharing statement. Although the requirement from the International Committee of Medic...

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.

BACKGROUND: Intrafraction motion may compromise the target dose in stereotactic body radiation therapy (SBRT) of tumors in the liver. Respiratory gating can improve the treatment delivery, but gating based on an external surrogate signal may be inaccurate. This is the first paper reporting on respiratory gating based on internal electromagnetic monitoring during liver SBRT.MATERIAL AND METHODS: Two patients with solitary liver metastases were treated with respiratory-gated SBRT guided by three implanted electromagnetic transponders. The treatment was delivered in end-exhale with beam-on when the centroid of the three transponders deviated less than 3 mm [left-right (LR) and anterior-posterior (AP) directions] and 4mm [cranio-caudal (CC)] from the planned position. For each treatment fraction, log files were used to determine the transponder motion during beam-on in the actual gated treatments and in simulated treatments without gating. The motion was used to reconstruct the dose to the clinical target volume (CTV) with and without gating. The reduction in D95 (minimum dose to 95% of the CTV) relative to the plan was calculated for both treatment courses.RESULTS: With gating the maximum course mean (standard deviation) geometrical error in any direction was 1.2 mm (1.8 mm). Without gating the course mean error would mainly increase for Patient 1 [to -2.8 mm (1.6 mm) (LR), 7.1 mm (5.8 mm) (CC), -2.6 mm (2.8mm) (AP)] due to a large systematic cranial baseline drift at each fraction. The errors without gating increased only slightly for Patient 2. The reduction in CTV D95 was 0.5% (gating) and 12.1% (non-gating) for Patient 1 and 0.3% (gating) and 1.7% (non-gating) for Patient 2. The mean duty cycle was 55%.CONCLUSION: Respiratory gating based on internal electromagnetic motion monitoring was performed for two liver SBRT patients. The gating added robustness to the dose delivery and ensured a high CTV dose even in the presence of large intrafraction motion.

Purpose. To study if partnership modifies the effect of gastrointestinal symptoms on quality of life after radiation therapy for prostate cancer. Material and methods. Using a study-specific questionnaire we conducted a cross-sectional follow-up of the occurrence gastrointestinal symptoms and quality of life after radiation therapy for prostate cancer. We obtained information from 874 prostate cancer survivors treated with radiation therapy at the Sahlgrenska University Hospital, Sweden between 1994 and 2006. In this paper we describe how partnership status affects the association between gastrointestinal symptoms and quality of life. Results. We found that unpartnered men with gastrointestinal symptoms reported a lower quality of life than unpartnered men without such symptoms. Unpartnered men with symptoms had an excess risk of low quality of life compared with unpartnered men without symptoms for those experiencing altered composition of stools, prevalence ratio 3.8 (95% CI 1.1–13.1), leakage, 3.6 (1.3–10.1), sensory bowel symptoms, 4.5 (1.6–12.8), and for urgency, 4.2 (1.2–15.1). We also found that unpartnered men with symptoms had an excess risk of low quality of life compared with partnered men with symptoms for those experiencing altered composition of stools, prevalence ratio 2.9 (95% CI 1.4–5.8), leakage 2.8 (1.2–6.4), sensory bowel symptoms 3.4 (1.5–7.4), urgency 2.6 (1.2–5.8), and for any gastrointestinal symptom 2.5 (1.3–4.9). Conclusion. Unpartnered men may represent a group that is specifically vulnerable to the distressful effects of gastrointestinal symptoms after radiation therapy for prostate cancer.

Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for D50 and γ50 were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship for a patient without pulmonary co-morbidities, caudally located tumor, no history of smoking, < 63 years old, and receiving no sequential chemotherapy was estimated as D500 = 34.4 Gy (95% CI 30.7, 38.9), γ500 = 1.19 (95% CI 1.00, 1.43). Individual patient risk estimates were calculated. The cumulative incidences of RP in the validation dataset were not significantly different in high/low-risk patients when doing risk allocation with the QUANTEC model (p = 0.11), but were significantly different using the individualized model (p = 0.006). C-indices were significantly different between the dose-only and the individualized model. Conclusion. This study presents a method to combine a published dose-response function with known clinical risk factors and demonstrates the increased predictive power of the combined model. The method allows for individualization of dose constraints and individual patient risk estimates.

Screening for distress is controversial with many advocates and detractors. Previously it was reasonable to assert that there was a lack of evidence but this position is no longer tenable. The question is now: what does the evidence show and, in particular, when is screening successful and when is screening unsuccessful? The aim of this paper is to review the most up-to-date recent findings from randomized and non-randomized trials regarding the merits of screening for distress in cancer settings.A search was made of the Embase/Medline and Web of knowledge abstract databases from inception to December 2012. Online theses and experts were contacted. Inclusion criteria were interventional (randomized and non-randomized) trials concerning screening for psychological distress and related disorders. Studies screening for quality of life were included.Twenty-four valid interventional studies of distress/QoL screening were identified, 14 being randomized controlled trials (RCTs). Six of 14 screening RCTs reported benefits on patient well-being and an additional three showed benefits on secondary outcomes such as communication between clinicians and patients. Five randomized screening trials failed to show any benefits. Only two of 10 non-randomized sequential cohort screening studies reported benefits on patient well-being but an additional six showed secondary benefits on quality of care (such as receipt of psychosocial referral). Two non-randomized screening trials failed to show benefits. Of 24 studies, there were 17 that reported some significant benefits of screening on primary or secondary outcomes, six that reported no effect and one that reported a non-significantly deleterious effect upon communication. Across all studies, barriers to screening success were significant. The most significant barrier was receipt of appropriate aftercare. The proportion of cancer patients who received psychosocial care after a positive distress screen was only one in three. Screening was more effective when it was linked with mandatory intervention or referral.Screening for distress/QoL is likely to benefit communication and referral for psychosocial help. Screening for distress has the potential to influence patient well-being but only if barriers are addressed. Quality of care barriers often act as a rate limiting step. Key barriers are lack of training and support, low acceptability and failure to link treatment to the screening results.

International comparisons have indicated low colorectal cancer (CRC) survival in Estonia, compared to other European countries. The objective of this paper is to analyse long-term survival as well as staging and treatment patterns of CRC in Estonia.The analysis included all incident cases of CRC diagnosed in Estonia in 1997 (n = 546), identified through the Estonian Cancer Registry and followed up for 10 years after diagnosis. Staging and treatment data were retrospectively collected from medical records. Relative survival rate (RSR) was used to estimate the outcome.The 5-year RSR was 51% for colon cancer and 38% for rectal cancer; the corresponding 10-year RSR was 50% and 39%. We observed no excess mortality for early disease. For stages II and III, the survival was markedly higher in colon cancer (5-year RSR 79% and 66%, respectively) compared to rectal cancer (66% and 30%, respectively). Around 30% of cases were diagnosed with distant disease. Among radically operated colon and rectal cancer patients, the 10-year RSR was 90% and 70%, respectively. Most patients with available pathological information had one to four lymph nodes examined. Survival has notably improved for colon cancer, but not for rectal cancer in Estonia. High proportion of cases with distant metastasis at first diagnosis along with inadequate staging and low proportion of patients treated with curatively intended surgery and appropriate chemotherapy and radiotherapy may have contributed to this outcome. Progress could be achieved by earlier diagnosis and implementing higher standards for staging and treatment. These conclusions are likely to be relevant also for other Eastern European countries.

Population-based relative survival is widely used as a method of monitoring the success of cancer control. This success may not be relevant only for an entire country but also regional developments over time are of interest. It would not only be important that the relative survival improved but also that the differences between regions decreased over time.In this paper the authors show how relative survival methods can be used to study such differences. In addition to standard methods, some more recently introduced approaches are used, most notably a method for checking the goodness of fit of the relative survival model. This gives confidence in the obtained results and provides additional insight when assumptions are not met.An analysis of cancers of the colon and ovary by cancer control region in Finland in 1953-2003 shows an overall improvement in relative survival, accompanied in colon cancer also by a decrease of differences in relative survival between the regions. Thus, the desired course was observed in colon cancer but not in cancer of the ovary.These results, applied to further sites, should lead to investigation of differences in cancer control policies between regions.

Cancer affects not only patients but also their loved ones. Material and methods. This paper presents a selective, narrative review of psychosocial consequences of cancer and its treatment for relatives of patients, including parents and siblings of children with cancer, children of parents with cancer and partners of adults with cancer. Results. Remarkably, most relatives adapt well to the cancer of a loved one. That is only a minority appears to be at risk for psychological morbidity. Bereavement has been found to impact psychological well being in the short-term, but it does also not appear to be a major risk factor for severe psychopathology. The exception being the loss of a child; this often appears to have intense and long-lasting effects on the parents. Furthermore, especially women were found to be at risk for distress. Conclusion. Future studies that focus on the interactions between patients and family members - parents, children and partners - are of great importance to further the field by providing more insight into the family dynamics of dealing with cancer. Such insights will offer tools for (refining) interventions for families in need.

Background. In 2009, the European Randomized Study of Screening for Prostate Cancer (ERSPC) was one of two studies to report interim data on the effect of screening for prostate cancer (PC) on the disease specific mortality. Contradictory results caused considerable discussion and misunderstanding in secondary literature. Methods. This document is based on a non systematic review of recent evidence for and against screening for PC, specifically considering three recently published randomized screening trials [1 3]. Results. The ERSPC data are based on a core age group of 162 387 men, aged 55 69 years, who were identified through population registries in seven European countries. Men were randomized between a screening group that received screening at an average of once every four years and a control group. After a median follow-up of nine years, a reduction in the rate of death from PC by 20% was shown which increased to 31% after adjusting for noncompliance and contamination. Overdetection and subsequent overtreatment (with a number needed to treat (NNT) of 48) are considered to be the major down sides of screening. The recently published 14-year results have shown that these down sides strongly depend on the duration of follow-up. In response to the outcomes of the ERSPC, several points of discussion have been brought up by various authors concerning the usefulness of screening considering benefits, harms and costs, the methodology of the ERSPC and the interpretation of its outcomes. Important issues to address regarding PC screening are addressed. Conclusions. This paper sheds a light on the controversial points of the ERSPC as well as on the priority issues of PC screening. On July 2, 2010 the Swedish section of ERSPC (Goteborg screening trial) published their results with a median follow-up of 14 years. With longer follow-up the data confirm the trend seen in improvement of PC mortality and suggest much more favorable future outcomes also with respect to the NNT to prevent one PC death.

This and the preceding issue of Acta Oncologica contain several papers adding to our understanding, and ability to predict, normal tissue morbidity in individual patients treated with radiotherapy ...

Little has been reported on the errors of setup and daily organ motion that occur during radiation therapy (RT) for esophageal cancer. The purpose of this paper was to determine the margins of esophageal motion during RT.The shift of the esophagus was analyzed in 20 consecutive patients treated with RT for esophageal cancer from November 2007. CT images for RT planning were used as the primary image series. Computed tomography (CT) images were acquired using an Elekta Synergy System, equipped with a kilovoltage-based cone-beam CT (CBCT) unit. The subsequent CBCT image series used for daily RT setup were compared with the primary image series to analyze esophageal motion. CBCT was performed before treatment sessions a total of 10 times in each patient twice a week. The outer esophageal wall was contoured on the CBCT images of all 200 sets.In the 200 sets of CBCT images, the mean (absolute) +/- standard deviation (SD) of setup errors were 2 +/- 2 mm (max, 8 mm) in the lateral direction, 4 +/- 3 mm (max, 11 mm) in the longitudinal direction, and 4 +/- 3 mm (max, 13 mm) in the vertical direction. Additionally, the mean +/- SD values of daily esophageal motion comparing the CBCT with RT planning CT were 5 +/- 3 mm (max, 15 mm) in the lateral direction and 5 +/- 3 mm (max, 15 mm) in the vertical direction.Our data support the use of target margins (between the clinical target volume and planning target volume) of 9 mm for day-to-day esophageal motion and 8 mm for patient setup in all directions, respectively.

Health decisions involve sharing information and making choices-even if the choice is to leave the decision to others. The way that information is delivered and understood by consumers across their cancer journey in turn influences the health decisions they take. A public health approach to the cancer journey considers the information needs of individuals and the structures and systems that facilitate the provision of credible and timely information. This paper examines emerging research that takes a public health approach to promote information-sharing and health decisions, identifies information-sharing mechanisms used by providers to facilitate shared decisions and evaluates decision support processes designed to improve information-sharing and self-care events. Evidence is presented to guide future research directions.

Background. Adult T-cell leukemia/lymphoma (ATL) is a severe disease caused by HTLV-I. This paper describes the clinicopathological and immunohistochemical findings of 52 cases of ATL with skin involvement and investigates whether there is any relationship between median survival time (MST) and histological patterns, primary cutaneous involvement and CD8 positivity. Material and methods. All cases were HTLV-I and HIV- and were clinically classified. HTLV-I proviral integration was investigated in atypical cases. Immunohistochemistry was performed using CD3, CD4, CD5, CD7, CD8, CD20, CD25, CD30 and CD45RO markers. Ki-67 was used to evaluate the proliferative index. Results. Twentyseven cases were primary, while 25 were secondary. Monoclonal viral integration was demonstrated in all atypical cases. Patterns resembling mycosis fungoides (MF) were found in 19 cases and anaplastic large-cell lymphoma (ALCL) in two cases. Fifteen cases had an atypical immunophenotype and expressed CD8. Primary cutaneous ATL had a longer MST (48 months) than the secondary cutaneous ATL (7 months) and the difference was statistically significant, but no statistically significant difference was found between the MST of CD8-positive and negative cases. Conclusions. It is important to differentiate between primary and secondary cutaneous ATL and classify the cases histologically in order to better evaluate the prognosis. The two forms of primary cutaneous ATL, primary cutaneous smoldering and primary cutaneous tumoral (PCT), should also be identified. The smoldering type presented a longer survival (58 months) and histological aspects suggestive of better prognosis in contrast to the PCT type that had a shorter survival (20 months) and histological characteristics suggestive of worse outcome.

Udgivelsesdato: 2008-null DBCG (Danish Breast Cancer Cooperative Group) constitutes a multidisciplinary organization established in 1975 by the Danish Surgical Society. The purpose involves first and foremost a nation-wide standardization of breast cancer treatment based on novel therapeutic principles, collaboration between experts handling diagnostic work-up, surgery, radiotherapy, medical oncology, and basic research, and, further, complete registration of relevant clinical data in a national data base attached to DBCG. Data are processed by the Secretariat personnel composed of statisticians, data managers, and data secretaries making current analyses of outcome results feasible. DBCG is run by the Executive Committee consisting of expert members appointed by their respective society. From 1978 the DBCG project gained widely accession from participating units, and since then nearly all newly diagnosed breast cancer incident cases are reported and registered in the national data base. Today, the data base includes approximately 80 000 incidents of primary breast cancer. Annually, the Secretariat receives roughly 1.5 million parameters to be entered into the data base. Over time DBCG has generated seven treatment programmes including in situ lesions and primary invasive breast cancer. Probands are subdivided into risk groups based on a given risk pattern and allocated to various treatment programmes accordingly. The scientific initiatives are conducted in the form of register- and cohort analysis or randomized trials in national or international protocolized settings. Yearly, about 4 000 new incident cases of primary invasive breast cancer and about 200 in situ lesions enter the national programmes. Further, about 600 women with hereditary disposition of breast cancer are registered and evaluated on a risk scale. The main achievements resulted in a reduction of relative risk of death amounting up to 20% and increased 5-year overall survival ascending from 60% to roughly 80%. This article is partly based on a Danish paper to be published in the Centenary Jubilee book of the Danish Surgical Society, 2008.

Today, the decision to treat breast cancer patients with endocrine therapy relies solely on tumor expression of two predictive factors, the estrogen receptor and the progesterone receptor. Expression of these hormone receptors are, however, not a guarantee for a response to treatment and patients who experience response at first may become resistant after prolonged treatment. This paper describes the use of preclinical models to identify mechanisms and new markers for endocrine sensitivity and resistance and the translation of these data to clinical utility.

Ionizing radiation is a well established carcinogen for human cells. At low doses, radiation exposure mainly results in generation of double strand breaks (DSBs). Radiation-related DSBs could be directly linked to the formation of chromosomal rearrangements as has been proven for radiation-induced thyroid tumors. Repair of DSBs presumably involves two main pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). A number of known inherited syndromes, such as ataxia telangiectasia, ataxia-telangiectasia like-disorder, radiosensitive severe combined immunodeficiency, Nijmegen breakage syndrome, and LIG4 deficiency are associated with increased radiosensitivity and/or cancer risk. Many of them are caused by mutations in DNA repair genes. Recent studies also suggest that variations in the DNA repair capacity in the general population may influence cancer susceptibility. In this paper, we summarize the current status of DNA repair proteins as potential targets for radiation-induced cancer risk. We will focus on genetic alterations in genes involved in HR- and NHEJ-mediated repair of DSBs, which could influence predisposition to radiation-related cancer and thereby explain interindividual differences in radiosensitivity or radioresistance in a general population.

Extracranial stereotactic radioablation (ESR) involves treating well-demarcated targeted tissues (e.g. tumor with minimal margin for set-up uncertainties) with very large doses of radiation in single or a few fractions with the intent of causing profound late tissue damage within the targeted volume. In such circumstances, considerable effort must be taken to reduce non-target tissue exposure to the high dose levels in order to prevent late complications to involved organs. Consequently, the following conditions for effective delivery of the ESR techniques have to be satisfied: 1) delivery of a high dose per fraction, i.e. 10-24 Gy; 2) delivery of only a few fractions per course of treatment (e.g. 1-4); 3) shaping of the prescription isodose surface conformally to the target surface; 4) delivery of a non-uniform dose distribution within the target with the highest dose in centrally located regions of hypoxia; 5) rapid fall-off of dose from the target volume to healthy tissue in all directions. In this paper it is shown that high doses per fraction in few fractions can be delivered to a variety of locations with both efficacy and acceptable toxicity (conditions 1 and 2). Conformal shaping of the high isodose surfaces is best accomplished by employing many beams (5-10) each with carefully milled apertures precisely coincident with the target projection (condition 3). Beam intensity modulation creating parabolic beam entrance fluence profiles both concentrates the highest dose in central regions of tumor hypoxia and increases fall-off gradients outside of the target (conditions 4 and 5). It is also shown that isotropic, highly non-coplanar beam arrangements avoiding oppositional fields allow more optimal fall-off gradients to normal tissue as opposed to coplanar treatments (condition 5).

This paper reviews patient and staff perceptions of cancer patients' psychological concerns and needs. An extensive literature search resulted in a total of 22 studies. Six of these concern staff ratings of hypothetical 'average' patients, and the main findings are that staff and patients are in relative agreement about the overall spectrum of concerns relevant to cancer patients, but less so regarding which concerns are of most importance to patients. Sixteen studies compare patient ratings with staff ratings of individual patients. The overall pattern of results indicates that staff tend to overestimate patient anxiety and emotional distress and show limited ability adequately to assess patient distress in terms of rank. Staff were able correctly to detect a majority of anxiety 'cases', while the identification of depression was less accurate. High detection rates for anxiety were obtained partly at the expense of staff also presuming anxiety in many non-distressed patients. Generally, there was better patient-staff agreement on the absence than the presence of patient anxiety and depression. Many studies were found to have serious methodological deficiencies and there is no clear evidence that patient-staff agreement is markedly better in studies fulfilling important methodological criteria. Several explanations of patient-staff discrepancies are discussed. Future research should be aimed at critically testing possible reasons for patient-staff disagreement and at investigating the consequences of such discrepancies.

The rapid growth of bioethics has injected a new style of analysis into medicine. It requires philosophical rigor, yet is deeply embedded in human situations that frustrate abstract thinking and are laced with subjective factors. These interlaced ethical and psychological components can lead to conflicts and dilemmas. Doctors, as experts and decision-makers, play a key role, but will benefit from additional skills to disentangle these situations. This paper notes ways in which patients, families and caregivers are newly vulnerable and delineates how ethical dilemmas and psychological issues mold or frustrate decision-making. To help physicians manage such cases, a method of systematic analysis, the 'situational diagnosis', and a related hierarchy of interventions, is described and illustrated with case examples.

The First Nordic Conference on Chemoresistance in Cancer Treatment was held in the Danish town of Helsingor on October 9th and 10th, 1997, under the auspices of the Nordic Cancer Chemoresistance Group (NCCG). The meeting focused on biochemical chemoresistance in a multidisciplinary approach. There were 19 oral and 15 poster presentations documenting recent advances in experimental and clinical research of drug transport mechanisms, DNA repair systems, detoxifying enzymes, drug target regulation, in vitro sensitivity tests, apoptosis inhibition, and strategies to circumvent chemoresistance. In the present paper we review the main issues that were addressed and discuss the findings with reference to the current literature in the field. The meeting demonstrated the plurality and the complexity of chemoresistance, which is a major obstacle to successful chemotherapy in cancer patients. The new insights to mechanisms of drug resistance and sensitization represent a useful basis for further development of strat...

Clinical research of high international standard is very demanding and requires clinical data of high quality, software, hardware and competence in research design and statistical treatment of data. Most busy clinicians have little time allocated for clinical research and this increases the need for a potent infrastructure. This paper describes how the Norwegian Radium Hospital, a specialized cancer hospital, has reorganized the clinical research process. This includes a new department, the Clinical Research Office, which serves the formal framework, a central Diagnosis Registry, clinical databases and multicentre studies. The department assists about 120 users, mainly clinicians. Installation of a network software package with over 10 programs has strongly provided an internal standardization, reduced the costs and saved clinicians a great deal of time. The hospital is building up about 40 diagnosis-specific clinical databases with up to 200 variables registered. These databases are shared by the treatme...

The present paper documents the calculation of radiation spectra and of radial dose distribution around a point source for 24 selected radionuclides. The radionuclides were ordered into three groups: Nuclides potentially useful for therapy by emission of Auger electrons: 51Cr, 64Cu, 67Ga, 73Se, 75Se, 77Br, 80mBr, 94Tc, 99mTc, 114mIn, 115mIn, 123I, 124I, 125I, 167Tm, 193mPt, and 195mPt, nuclides potentially useful for therapy by alpha-particles with additional emission of Auger electrons: 212Bi, 211At and 255Fm, and nuclides potentially useful for electron Auger-therapy with simultaneous PET diagnosis: 73Se, 94Tc and 124I. The calculations imply strongly the development of labelled DNA-seeking compounds useful as carrier for the Auger- and Coster-Kronig electron-emitting radionuclides.

This paper offers a general mathematical approach to dose distribution optimization which allows tumours with different degrees of complexity to be considered. Two different biological criteria - A) keeping the control probability of the different parts of the tumour (local tumour control probability) uniform throughout the tumour and B) minimizing the mean dose delivered to the tumour are studied. For both criteria we impose the requirement that the whole tumour control probability be kept on a certain desired level. It is proved that the adoption of the first criterion requires a dose distribution logarithmic with the cell density and proportional to the inverse of the cell radiosensitivity while the adoption of the second criterion necessitates a homogeneous dose distribution when the cell radiosensitivity is constant. The corresponding formula for the dose distribution in case of heterogeneous cell radiosensitivity is also given. The two criteria are compared in terms of local tumour control probability and mean dose delivered to the tumour. It is concluded that maintaining constant local tumour control probability (criterion A) may be of greater clinical importance then minimizing the mean dose (criterion B).

Effective treatment for breast cancer can produce a reasonably good ten-year survival rate in comparison to many other cancer sites. Nevertheless, the potential psychological, sexual and physical dysfunction caused by both the diagnosis and treatments can have a deleterious impact on the quality of a woman's life. The range of possible treatments may have similar outcomes in terms of response and survival, but can produce very different effects on emotional well-being. Therefore, monitoring quality of life in breast cancer should be a mandatory part of follow-up in clinical trials. Data derived from various studies of quality of life can also be used to assist the doctor and patient in decision-making about treatment options. Furthermore, assessment of quality of life can help identify those patients who might profit from psychosocial interventions. In this paper some of the instruments used to assess quality of life in breast cancer will be discussed.

The availability of constantly more sophisticated algorithms and methods for dose planning (denoted 'level 3' procedures by the ICRU) makes it possible to use accordingly more complex treatment techniques. Such procedures have the potential of reducing irradiation of organs at risk and other healthy tissue. However, they suffer from a substantially more difficult set-up of the patient and verification of the treatment. This will introduce additional sources of error, systematic as well as random, which will be of importance for dose reporting. The purpose of this paper is to point out some of these problems and to suggest a method for reporting which is the least sensitive to these 'new' sources of error.

This paper reviews the current status of conservative treatment for early breast cancer. While the first patients were treated with such techniques more than 60 years ago, it is during the last decade that randomized trials have confirmed that such treatment is comparable to mastectomy in preventing breast cancer death. Radiotherapy to the breast after local tumour excision is important to prevent local breast relapse, but it is not clear whether it has any influence on the risk of distant metastases. Several questions remain to be answered. While most investigators agree that the breast should receive a radiation dose of about 50 Gy in 5 weeks, there is no general agreement about the need for a tumour bed booster dose. Considering patients with tumour infiltration at the surgical resection line for whom it is not possible for cosmetic reasons to perform re-resection, it is not clear whether an acceptable local control rate can be achieved through application of a high booster dose in the tumour bed. More trials are needed to show whether certain patients with small invasive carcinomas should be treated with wide local excision without radiotherapy. The need for radiotherapy after local excision for small intraductal (ductal carcinoma in situ) cancers is being addressed in ongoing trials.

Transient symptoms due to injury of the intestinal mucosa occur in the majority of patients receiving radiation therapy for pelvic or intra-abdominal neoplasms. Late (chronic) radiation enteropathy, although less common, is a more serious condition, associated with high morbidity and mortality. The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. As a result of recent clinical and experimental studies, considerable knowledge about the pathogenesis, dose-response relationship, and time-course of development of late radiation enteropathy has been obtained. Also, the advent of new animal models has facilitated studies of time-dose-fractionation relationships in the intestine. The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury.

Death cause registers and cancer incidence registers are often used to elucidate progress (or lack of progress) in the battle against cancer. Trends in the age-adjusted mortality rate of cancer or of specific cancer types may thus mirror the overall effect of anticancer interventions (prevention, early diagnostics, treatment), but are often influenced by changes in the death cause diagnostics or in the coding routines at the registers. Relative survival rate (or its inversion, relative mortality rate) is sometimes used in order to elucidate improvement due to treatment. It is independent of the death cause diagnoses but often seriously influenced by changes in diagnostics of incident cancer; earlier diagnosis and increased detection of non-fatal cases may thus give an improved relative survival rate, quite unrelated to any improvement in the treatment. In the present paper the excess mortality rate is introduced as a measure which can give additional information concerning effects of anticancer interventions. In contrast to age-adjusted mortality rate it is not dependent on death cause diagnoses or coding routines, and in contrast to relative survival it is independent of the rate of non-fatal incident cancer cases.

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The median period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awareness of this complication is important in order to have an early diagnosis so as to limit disability.

The paper presents descriptive data concerning relationships between age, menopausal status and steroid receptor content in primary breast carcinoma. The study was based on 2,329 women with primary breast carcinoma diagnosed in Stockholm county during 1980-1983. Oestrogen (ER) and progesterone receptor (PgR) content was determined using the isoelectric focusing technique. All analyses were done in one laboratory. There was a gradual increase in mean ER values with age. Premenopausal patients had lower mean ER values than peri- and postmenopausal patients of the same age. In contrast, PgR levels were similar in different age-groups. This could be a result of an insufficient stimulation of the tumour cells via the ER pathway. It is also possible that the PgR stimulation is maximal already at ER values below those found in old patients. It is concluded that steroid receptor content measured with commonly used ligand assays may reflect both biological properties of the tumour cells as well as influences by nontumoural factors, e.g. the endogenous levels of sex hormones.

Time-related trends in age-standardized cancer mortality have been suggested to be the best single measure of the progress--or lack of progress--in cancer control measures. The paper presents data on trends in Sweden during 1960-1986. From the middle of the 1970s, total cancer mortality decreased significantly among both males and females. The estimated annual decrease between 1975 and 1986 was 0.5-1.2%. Current Swedish trends are thus in keeping with the goal stated in the European Community's action programme 'Europe against cancer': a 10-15% decrease in total age-standardized cancer mortality by the year 2000. This goal might even be too conservative, because most of the cancer control measures in 'Europe against cancer' will not be able to enhance the current downward trends until the early 1990s.