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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, pretreatment information and evaluation, treatment choices, as well as follow-up. [ABSTRACT FROM AUTHOR]

Introduction. An at least 3-month expected survival is a common inclusion criterion in cancer treatment trials, including advanced pancreatic cancer phase III studies. Published survival curves for advanced pancreatic cancer however seem to reflect a substantial survival shortfall. We wanted to assess the strength of this observation and search for an explanation by reviewing the literature. Methods. A Medline and EMBASE search was done for chemotherapy or chemotherapy based phase III studies in advanced pancreatic cancer published since 1997. Similar search was done at the American Society's of Clinical Oncology web site for abstracts presented since 2000. Three months mortality was based on the survival curves presented. Results. Fourteen papers and five abstracts met our criteria and are included in our review. Six thousand two hundred and twelve patients participated in these trials and 1 447 (23.3%) died in the first 3-month period. Figures were worse in patients with metastases and poorer performance status. Assuming that most deaths during treatment happened during the first 3-months, cause of death was reported in only 40 cases (2.8%). Progressive cancer was reported as cause of death in 21 of these cases. Less frequent causes of death were reported to be infections, 'complications of cancer', thromboembolic events and renal failure. Discussion. Overall treatment-related deaths represent a very small percentage of the deaths happening during the 3-month period, and are unlikely to be under-reported given the Good Clinical Practice oversight of these trials. Progressive cancer is likely to be an important cause of early mortality but given the very select nature of the trial-related population this cannot explain the phenomenon of 3-month early death burden of 23.3%. Our hypothesis, supported by multiple autopsy series, is that early death burden in advanced pancreatic cancer trial patients is likely to be due to under-reported vascular thromboembolic events. Thromboprophylaxis needs to be addressed in future trials. [ABSTRACT FROM AUTHOR]

Two treatment options are widely used for the cure of T1 glottic squamous cell carcinoma: radiotherapy and surgical removal. There is ongoing controversy about whether laser excision should be offered to patients with T1 glottic carcinoma. The purpose of this study is to present a review of studies dealing with treatment outcome after laser excision of T1 glottic carcinoma. Eighteen original papers on outcomes were identified. Recurrence rates ranged from 4% to 35%. The disease-specific survival rate at 5 years was found to be from 89% to 100% and crude survival from 74% to 100%. Of the six studies dealing with voice quality, radiation therapy was found to be more effective in preservation of the voice in three, while in the other three studies, no significant difference could be detected. With respect to costs of treatment, in three out of four studies laser surgery was found to be the more economical treatment option. Laser surgery seems to provide comparably low recurrence rates and high disease-specific survival as compared with radiotherapy. In T1 cancer, laser resection leaves the patient with a poorer voice quality than is the case with radiation therapy, but laser treatment seems to be the cheaper option. [ABSTRACT FROM AUTHOR]

Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC occurs more frequently than expected in immunosuppressed subjects, especially in organ transplant recipients. The current literature comprises reports of 79 organ transplant recipients with MCC. The risk of MCC in organ transplant recipients is increased up to 66-182-fold compared with the general population. In addition to the increased risk of developing MCC, immunosuppressed individuals have poorer MCC-specific survival. The aim of this review article is to familiarize organ transplant doctors with this unique and clinically challenging skin cancer, and to provide recent data on the diagnosis and current treatment recommendations for an immunosuppressed population. [ABSTRACT FROM AUTHOR]

Compared to non-smokers, smokers have reduced effects of cancer treatment, and increased risk of treatment-related toxicity. Quitting smoking can improve treatment effects and reduce side effects. This study reports on the potential impact of a smoking cessation program on smoking cessation rates among patients in cancer treatment. Cancer patients 18 years and older who smoked, with survival prognosis ≥12 months, not suffering dementia or other mental illness, and who were referred to cancer treatment at six Norwegian hospitals were invited to participate. The study took place from 2017 to 2020 and used a pre-test-posttest non-equivalent control group design. The intervention group received structured smoking cessation guidance based on Motivational Interviewing combined with cost-free nicotine replacement products, while the control group received standard smoking cessation treatment. Self-reported smoking status were registered at baseline and at 6 months' follow up. 76% of patients smoked at baseline and 44% at follow-up in the intervention group, correspondingly 72% and 49% in the control group. In an analysis of differences in within-person change, the reduction in the intervention group was 13 percentage points larger (95% CI = (0.25, −0.005), p = 0.041). Adjusting for gender, age, education, labour market participation and partnership status did not attenuate the estimated effect (18 percentage point difference, 95% CI = (−0.346, −0.016), p = 0.032). Demographic factors and dropout rate differed somewhat between the groups with a higher dropout rate in the intervention group, 54% vs. 51%, respectively). Offering a structured smoking cessation program based on Motivational Interviewing and cost-free nicotine replacement products to cancer patients can increase cessation rates in comparison to standard smoking cessation care. [ABSTRACT FROM AUTHOR]

Background and objectives. Cancer-related cognitive impairment has been acknowledged as a substantial limiting factor in quality of life among cancer patients and survivors. In addition to deficits on behavioral measures, abnormalities in neurologic structure and function have been reported. In this paper, we review findings from the literature on cognitive impairment and cancer, potential interventions, meditation and cognitive function, and meditation and cancer. In addition, we offer our hypotheses on how meditation practice may help to alleviate objective and subjective cognitive function, as well as the advantages of incorporating a meditation program into the treatment of cancer patients and survivors for cancer-related cognitive deficits. Findings. Various factors have been hypothesized to play a role in cancer-related cognitive impairment including chemotherapy, reduced hormone levels, proinflammatory immune response, fatigue, and distress. Pharmacotherapies such as methylphenidate or modafinil have been suggested to alleviate cognitive deficits. While initial reports suggest they are effective, some pharmacotherapies have side effects and may not relieve other symptoms associated with multimodal cancer treatment including sleep disturbance, nausea and pain. Several recent studies investigating the effects of meditation programs have reported behavioral and corresponding neurophysiological modulations that may be particularly effective in alleviating cancer-related cognitive impairment. Such programs also have been shown to reduce stress, fatigue, nausea and pain, and improve mood and sleep quality. Conclusions. With the increasing success of cancer treatment and the ability to return to previous family, social, and work activities, symptom management and quality of life are an essential part of survivorship. We propose that meditation may help to improve cancer-related cognitive dysfunction, alleviate other cancer-related sequelae, and should be fully investigated as an adjuvant to cancer treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Worldwide, the number of cancer survivors is increasing, owing to improvements in cancer therapy, resulting in an increased need to address the physical and mental sequelae of cancer. This paper introduces a Danish psychosocial cancer intervention and presents the baseline characteristics of the cancer survivors with respect to cancer site, sociodemographic variables, social network, lifestyle, self-rated health and the prevalence of cancer-related late effects. The study is part of the FOCARE research project, in which the long-term effects of the rehabilitation programme are evaluated systematically. The study is based on data from a self-administered baseline questionnaire filled in by 2 174 cancer survivors who registered for a 1-week, publicly paid rehabilitation retreat and were invited to participate in the FOCARE study in the period 25 November 2002 to 31 December 2005. The response rate at baseline was 86% (n = 1876). Most participants were younger women with breast cancer. They were generally well educated and working. The cancer survivors reported having comprehensive social networks and being physically active. Several cancer-related symptoms were reported by women with cancers at selected sites, of which fatigue was the most prevalent. More than half reported good-to-excellent self-rated health, while fair-to-poor health was reported by 40%, most of whom were survivors of lung (56%) and haematological (48%) cancers. The results indicate that Danish cancer survivors experience considerably reduced physical health, possibly as late physical effects of treatment. The problems reported by the cancer survivors suggest that cancer rehabilitation should include these aspects of living after cancer and take account of differences among cancer survivors with regard to cancer site, sex, age, family, working status and social position. These challenges might be addressed optimally in multi-dimensional rehabilitation programmes. [ABSTRACT FROM AUTHOR]

Purpose. Due to the improved prognosis of many forms of cancer, an increasing number of cancer survivors are both willing and able to return to work after their treatment. This has increased interest in studying work and cancer-related issues. The purpose of this paper is to give an overview of research on the impact of cancer on employment and work ability, on the effect of psychosocial factors on survivors' well-being, and to indicate research needs for the future. Results. Studies have shown that the majority of cancer survivors are able to continue working. There is, however, a group of cancer survivors who suffer from impaired health as a result of their illness, and this impairment sometimes leads to a decreased ability to work, or even disability. Employment and impaired work ability has most commonly been found to be associated with cancer type, type of treatment, health status, education and physical workload. The few studies that have focused on the effects of psychosocial factors in work life suggest that social support from occupational health services, and workplace accommodations for illness affect cancer survivors' return to work. Conclusions. More research is needed on the impact of social factors at work, which seem to play an important role in cancer survivors' ability to continue working. [ABSTRACT FROM AUTHOR]

Background and Purpose. Fatigue is one of the most common and troubling symptoms in cancer survivors. In this paper we review information about cancer related fatigue in survivors of breast cancer and Hodgkin's disease, discuss some of the potential biological mechanisms for this problem in cancer survivors, and briefly discuss potential interventions. Findings. Cancer-related fatigue persists long after cancer treatments end, and is associated with more intensive treatments (combined chemotherapy and radiation therapy) in these cancers. Fatigue prior to the onset of treatment is a strong predictor of persistent fatigue. Studies in breast cancer survivors suggest elevated levels of pro-inflammatory cytokines in association with persistent fatigue, as well as abnormalities in the hypothalamic-pituitary axis. Psychosocial and physical activity interventions have been shown in some studies to alleviate fatigue. Conclusions. Recognizing the syndrome of cancer-related fatigue is a high priority for the many cancer survivors who continue to experience this complaint as a chronic health problem. [ABSTRACT FROM AUTHOR]

This paper deals with some of the musculo-skeletal complication that can occur after cancer treatment. In particular, we focus on Cancer Treatment Induced Bone Loss (CTIBL) and the musculo-skeletal complications that can occur in patients treated for extremity sarcoma. In addition we discuss peripheral neuropathy, musculo-skeletal pain and briefly mention some of the complications related to radiotherapy. CTIBL is mostly studied in breast cancer and prostate cancer survivors. The cause in these groups is mainly due to treatment induced hypogonadism. Other causes of CTIBL are indirect or direct cause of chemotherapy, physical inactivity and inadequate intake of vitamin D and calcium. Treatment of CTIBL consists of diet and lifestyle changes and pharmacological intervention. Extremity bone sarcomas constitute a special group since they often experience mutilating surgery and heavy combination chemotherapy. The treatment results in worse function than the normal population and the amputated usually have lower physical functioning than patients treated with limb sparing surgery (LSS). However, most studies fail to show differences in quality of life between the amputated and LSS. Most of the studies performed on musculo-skeletal sequelae have been done on survivors of childhood cancer, breast cancer or prostate cancer. More studies among the other cancer groups are needed to reveal the extent and prevalence of these complications. [ABSTRACT FROM AUTHOR]

Rehabilitation of cancer patients include a broad range of activities aimed at information, counselling, advices on possible change of lifestyle and behaviour, psychological support, social welfare questions, ways of coping with side-effects of the anti-carcinogenic treatment given and additional treatment of numerous clinical problems. The change in the age distribution combined with the growing number of cancer survivors and the scarce economic resources allocated to 'after-treatment' clinical follow-up of cancer patients, even in the Scandinavian countries characterised by their public tax financed health system, emphasize the need for screening of rehabilitation needs among cancer patients. There is a need to identify patients in need for psychological and social intervention. However, this intervention among cancer patients in need has to be based on results achieved in clinical studies. This paper gives a brief introduction to the field of rehabilitation research and indicates a number of areas in which research would be of benefit for the clinical organisation of rehabilitation activities. These areas include the implication of social inequality, a characterisation of cancer patients who rehabilitate successfully, the gender perspective in rehabilitation, the age perspective, how to establish cancer disease specific rehabilitation modules, family and community aspects of rehabilitation, the dilemma between individual responsibility for lifestyle changes and feelings of guilt and the need for models which can determine the best timing of the intervention among cancer patients. [ABSTRACT FROM AUTHOR]

In Sweden, radioactive iodine for thyroid diagnostics and therapy was introduced by Jan Waldenström (1906–1996) and Bengt Skanse (1918–1963). The paper describes the start of the clinical use of radioiodine, the various iodine isotopes available, measurement techniques and dosimetry. There are still problems to solve in relation to an optimal clinical use of radioiodine. One of the remaining challenges is to get consensus about the goal of the treatment of hyperthyreosis, as well as about a method for individual absorbed dose calculations. Careful dose estimates will prevent unnecessary radiation exposure and constitute a base for a future optimised radioiodine therapy. For the dose calculation, it is important to understand if there is any clinically significant temporary reduction in the ability of thyroid tissue to trap or retain 131I-iodide following prior administration of a diagnostic activity of 131I-iodide (stunning of the thyroid). This may be of special concern in connection with treatment of thyroid cancer and its metastases. Finally, the production capacity, availability and delivery of 123I have to be improved to increase clinical access to this radionuclide, which is optimal for diagnostic imaging and which gives lower absorbed dose and therefore also less risk for thyroid stunning than 131I. [ABSTRACT FROM AUTHOR]

Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications. [ABSTRACT FROM AUTHOR]

Angiotensin converting enzyme inhibitors (ACEi) prescribed for cardiovascular and renal disease since 1980 are widely atoxic and several experimental studies and one epidemiological study have demonstrated an effect of ACEi on cancer. ACEi has the effect of modifying gene expression; inhibiting proliferation and invasion of cancer cells; reducing endothelial cell migration and angiogenesis in vitro, whereas tumour growth and metastasis were inhibited in vivo. Several mechanisms of action are possible but inhibition of matrix metalloprotease activity, reduced expression of vascular endothelial growth factor and interference with the renin-angiotensin system were demonstrated by the experimental studies. In this paper we review the laboratory investigations and epidemiological studies on the anti-cancer actions of ACEi and present a summary of the evidence regarding the potential use of ACEi in cancer treatment. [ABSTRACT FROM AUTHOR]

This paper is based on a lecture given during the Oncological Forum, Oslo, in November 2002. Long-term morbidity in cancer survivors is exemplified by results of clinical research in testicular cancer survivors (TCSs). The most serious complication is the development of second, non-germ cell malignancies (relative risk [RR]: 1.4-1.6). After infradiaphragmatic radiotherapy, most solid malignancies are diagnosed within or near the target volume. Combined chemo-radiotherapy increases this risk. Chemotherapy-induced leukaemia is usually reported after 4-7 years. After 3 or 4 cycles of cisplatin-based chemotherapy, 15-20% of TCSs suffer from peripheral sensory neuropathy, Raynaud-like phenomena and/or ototoxicity. Hypogonadism is observed in 16%. The risk of cardiac complications is increased by hypercholestorolaemia and abnormal body mass. Pelvic radiotherapy and cisplatin-based chemotherapy are followed by transient oligo/azospermia with recovery after 6-12 months. The risk of surgery-related 'dry ejaculation' is significantly reduced after unilateral and nerve-sparing retroperitoneal lymph node dissection, but infertility remains a long-term problem in 10-15% of survivors. Most TCSs describe their quality of life as comparable with that of the age-matched male general population. Not all long-term complications are avoidable after curative treatment of cancer. Knowledge of post-treatment long-term morbidity is essential for early recognition and treatment of late complications, and enables adequate counselling of new cancer patients. [ABSTRACT FROM AUTHOR]

The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFα. The therapeutic gene (TNFα) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments. [ABSTRACT FROM AUTHOR]

To ensure that all citizens have equal access to high-quality cancer diagnosis and care, the EU4Health Programme, Europe's Beating Cancer Plan, and Horizon Europe's Cancer Mission propose Comprehensive Cancer Infrastructures in every European Union Member State. It is therefore important to establish the basic principles for high-performing cancer networks and a methodology for evaluating their quality and effectiveness. This article describes methods and standards/indicators for network evaluation found in literature, gives a comparative overview of the new OECI European Cancer Network Quality standards, and proposes principles for evaluating the performance of Comprehensive Cancer Networks as a basis for continuous improvement. We performed a scoping literature review on methods and standards/indicators for care-network evaluation. We then compared the OECI set with literature findings, categorised standards that were similar, reflected on standards that were different, and deduced principles for quality standards for cancer networks. Of 1002 articles identified, 17 reported on evaluation methods and/or (mostly) qualitative indicators. Sixteen studies described indicators/standards for evaluating care networks, critical success factors or desirable outcomes. Of the 54 present OECI standards, 32 had a literature equivalent. No literature equivalent was found for 22 standards, especially on those related to the combination of care and research. The proposed OECI evaluation methods (survey, document review, and interviews) were all reported in the literature. From the conformity of these results, we deduced 8 principles for standards evaluating the effectiveness of Comprehensive Cancer Networks. Research on the evaluation of the effectiveness of care networks is scarce. Evaluation methods vary and are often single time-point assessments. The OECI set contributes to establishing clear principles and standards to evaluate the effectiveness of Comprehensive Cancer Networks. [ABSTRACT FROM AUTHOR]

Prevalence of peripheral neuropathy (PN) has been studied in patients undergoing treatment with taxanes, platinums and vinca alkaloids. The prevalence is unknown in the general oncological cancer population, characterized by advanced age, comorbidities and heterogeneous treatments. A cross-sectional survey was administered to all adult patients, attending outpatient services at three Danish departments of oncology. The survey contained the EORTC-CIPN20, the EORTC-QLQ-C30, the GAD7 and PHQ9 questionnaires. A high PN symptom score was defined as a summary score ≥30 points on the CIPN20. P-values were adjusted for multiple testing. With an overall response rate of 83% (2839 patients), prevalence of PN was 17% overall, varying from 6 to 33% between diagnosis groups. A high score was more common among females (19 vs. 14%, p =.008), smokers (21 vs. 15%, p =.04), patients living alone (21 vs. 15%, p =.002) and patients using cannabis (29 vs. 15%, p <.001), as well as patients suffering from diabetes (26 vs. 16%, p <.001), cardiac heart disease (27 vs. 16%, p <.001), arthritis (32 vs. 15%, p <.001) or chronic obstructive pulmonary disease (25 vs. 16%, p =.01). High score patients were also older (69ys vs 67ys, p =.048) and more likely experiencing polypharmacy (OR = 3.38 [95% CI, 2.64;4.35]). Patients with a high CIPN20 symptom score scored worse on all EORTC QLQ-C30 function and symptom scales. The mean adjusted C30 SumScore difference was −18.66 ([95% CI, −20.31; −17.02], p <.001). Symptoms of PN are experienced widely across cancer groups in the oncology setting. PN symptoms were associated with clinically relevant worse health-related quality of life and with patient-related factors as living alone, various comorbidities, polypharmacy, and cannabis use. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses several articles published within issue on topics including proton therapy indications and strategies for identification of patients for proton therapy, property of proton therapy, and patient's perspective in proton therapy.

Background: The IAEA/WHO postal dose audit programme has been operating since 1969 with the aim of improving the accuracy and consistency of dosimetry in radiotherapy in low-income and middle-income countries world-wide. This study summarises the 50 years' experience of audits and explores the quality of reference dosimetry in participating radiotherapy centres throughout the years. Material and methods: During the IAEA/WHO postal audits the dose determined from the mailed dosimeter is compared with that stated by the participant. Agreement to within ±5% is regarded acceptable whilst deviations outside ±5% limits trigger follow-up actions. Of particular interest in this study was the dependence of clinical dosimetry quality on factors related to the centre infrastructure and expertise in dosimetry of its staff. Results: The IAEA/WHO dose audit programme noted great increase in the overall percentage of acceptable results from about 50% in its early years to 99% at present, although there is some variability of results amongst participating countries. Whereas results for younger radiotherapy machines show the agreement rate between the measured and the stated doses well above 90%, for those over 20 years old the rate dropped to <80%. Linac dosimetry was always better than 60Co dosimetry and multi-machine centres generally performed better than single machine centres equipped with cobalt alone. Second and subsequent participation in audits showed higher quality dosimetry than the first participation. The implementation of modern dosimetry protocols resulted in more accurate dosimetry than the use of the older protocols. Conclusions: Over the 50 years that the IAEA has accumulated dosimetry audit data, practices in radiotherapy centres have significantly improved. Higher quality dosimetry confirmed in audits is generally associated with better infrastructure and adequate dosimetry expertise of medical physicists in participating centres. [ABSTRACT FROM AUTHOR]

Profiles Sakari Mustakallio, a cancer doctor and head of the Radiotherapy Department in Helsinki, Finland. Educational background of Mustakallio; Work achievements; Contributions to cancer treatment.

Background:To evaluate local control (LC), survival and toxicity in anal cancer patients treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy at a single institution. Material and methods:From August 2010 to May 2015, 26 patients were treated at our institution with IMRT and concurrent 5-fluorouracil/mitomycin-C (5-FU/MMC) for localized squamous cell carcinoma of the anal canal (SCCAC). Radiotherapy (RT) with 50.4–60 Gy was delivered with a sequential boost in 31%, and a simultaneous-integrated boost (SIB-IMRT) in 69% of cases. Initial staging was based on PET-CT and MRI. Clinical measures of interest were the influence of PET-CT on staging and treatment planning, LC, disease free survival (DFS), overall survival (OS), colostomy free survival (CFS) and toxicities. Results:Median age was 61 years, 22 patients (85%) were female, and no patient was HIV-positive. The proportion of patients with stage I, II, IIIA and IIIB disease was 15%, 35%, 23% and 27%, respectively. PET-CT modified the extent of nodal disease in 9/23 cases (39%) and lead to major changes in treatment planning in 4/23 patients (17%). MRI was more accurate at identifying T4 disease. RT was delivered at full dose in 26 patients (100%) and chemotherapy in 22/26 patients (85%). Two patients (7.7%) required RT breaks. Median follow-up was 35 months [IQR: 19–52]. The 2-year LC, DFS, OS and CFS were 100%, 100%, 100% and 92%. Acute grade ≥3 dermatitis and diarrhea occurred in 73% and 8% of cases, respectively. Grade 3–4 neutropenia was seen in 10/23 patients (43%). Four patients (15%) developed chronic grade 2 GI toxicity. Conclusions:PET-CT provided additional information leading to major changes in treatment planning for 17% of patients. Considering our excellent outcomes, routine use of PET-CT as standard staging modality and IMRT planning procedure appears justified for patients with SCCAC. [ABSTRACT FROM PUBLISHER]

Appropriate medical decision-making in patients with keratinocyte skin cancer (KSC) can be challenging, especially in those with a limited life expectancy (LEx). Treatment should be beneficial for the individual patient, the risk of both over- and under-treatment should be carefully considered, and deviation from guideline recommendations may be necessary. In this study retrospective analysis was performed to determine the influence of age and comorbidity, both factors strongly related to limited LEx, on KSC management in daily practice. After analysis of 401 patients it was found that management in patients with KSC is not influenced, or is only minimally influenced, by high age and comorbidity. Better integration of aspects related to a limited LEx in KSC management might optimize care and prevent overtreatment. Future research on the general prognostication, prediction of the patient burden caused by tumour and treatment, and time-to-benefit in KSC management is strongly recommended. [ABSTRACT FROM AUTHOR]

Background:Neoadjuvant therapy response correlates with survival in multiple gastrointestinal malignancies. To potentially augment neoadjuvant response for pancreas adenocarcinoma, we intensified treatment with stereotactic body radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we analyzed whether the College of American Pathology (CAP) tumor regression grade (TRG) at pancreatectomy correlated with established response biomarkers and survival. Materials and methods:We identified borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer patients treated according to our institutional clinical pathway who underwent surgical resection with reported TRG (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19-9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT. They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression-free (PFS) survival were estimated and compared by Kaplan–Meier and log-rank methods. Univariate ordinal logistic regression correlated TRG with baseline, restaging and change in CA19-9 and the PET maximum standardized uptake value (SUVmax). Results:Restaging level and decrease in CA19-9 correlated with improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30). The TRG groups had similar OS and PFS except the TRG 0 (complete response) group. Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS 13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual isolated tumor cells had similar outcomes to the other TRG 1-3 patients. Conclusion:Pre-operative PET-CT and CA19-9 response correlate with histopathologic tumor regression. Patients with complete pathologic response have superior outcomes, suggesting a rationale for intensification and personalization of neoadjuvant therapy in BRPC and LAPC. [ABSTRACT FROM PUBLISHER]

Photodynamic therapy (PDT) is an alternative to surgery for Bowen's disease. This monocentric retrospective study included 105 patients with Bowen's disease, treated with PDT between 2007 and 2013, who received a total of 151 different PDT fields. Comparison of immunocompromised and non-immunocompromised patients revealed that the former often had a previous history of squamous cell carcinoma (SCC; p = 0.004) and received more PDT fields (p = 0.007) than the latter. At least one SCC occurred post-PDT in 16 out of 105 patients in a PDT field. However, many of the patients were at risk of SCC and the possibility that the lesion did not have a mixed histology at baseline, but might simply be a transformation of non-PDT-responsive Bowen's disease, cannot be excluded. Although it is rare, patients should be closely monitored for SCC post-PDT. [ABSTRACT FROM AUTHOR]

BackgroundWe characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). MethodsRetrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994–2011 with a minimum six months of follow-up or an event defined as relapse or death. ResultsHistologies included peripheral T-cell lymphoma–not otherwise specified (PTCL–NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16–103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III–IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10–75). ConclusionsDespite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3. [ABSTRACT FROM PUBLISHER]

ObjectiveTo evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments. MethodsTen patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires. ResultsDiagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD ± 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10–20) min. After a median follow-up of 12 (3–22) months, six patients (60%) were alive. ConclusionsObjective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3–22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting. [ABSTRACT FROM PUBLISHER]

PurposeThe aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal distribution of recurrences, and the outcome of salvage treatment in a contemporary cohort of HNC patients. MethodsThe study evaluated a cohort of 2062 consecutive patients treated with curative intent at Aarhus University Hospital from 1 January 2000 to 31 December 2013. The database of DAHANCA contained recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. ResultsFailures of the 567 patients were primarily in T-site (65%) followed by N-site (36%) and M-site (22%). The vast majority of the first recurrences occurred within the first years after primary treatment; 62%, 82%, and 91% within the first, second and third year, respectively. Totally, 51% were amenable for salvage treatment, and 44% benefited from salvage in terms of a complete response. Permanent tumor control was observed in 128 patients (23%) after one or two salvage attempts. The highest salvage rate was recorded in patients with primary glottic carcinoma (41%) and the lowest among hypopharyngeal cancers (2%). Asymptomatic recurrence was recorded in 12% of all recurrences and this was found to be a positive prognostic factor for disease-specific survival, as they had significantly better outcome after salvage. ConclusionOur data support the usefulness of specialized FU in terms of early detection of recurrent disease. In particular patients with silent recurrences benefited from early detection, as they had a significantly lower risk ratio of death from primary HNC. [ABSTRACT FROM PUBLISHER]

Background. A planning study investigated whether reduced target volumes defined on FDG-PET/CT during radiotherapy allow total dose escalation without compromising normal tissue tolerance in patients with esophageal cancer. Material and methods. Ten patients with esophageal squamous cell carcinoma (SCC), candidate to curative-intent concomitant chemo-radiotherapy (CRT), had FDG-PET/CT performed in treatment position, before and during (Day 21) radiotherapy (RT). Four planning scenarios were investigated: 1) 50 Gy total dose with target volumes defined on pre-RT FDG-PET/CT; 2) 50 Gy with boost target volume defined on FDG-PET/CT during RT; 3) 66 Gy with target volumes from pre-RT FDG-PET/CT; and 4) 66 Gy with boost target volume from during-RT FDG-PET/CT. Results. The median metabolic target volume decreased from 12.9 cm3 (minimum 3.7-maximum 44.8) to 5.0 cm3 (1.7-13.5) (p = 0.01) between pre- and during-RCT FDG-PET/CT. The median PTV66 was smaller on during-RT than on baseline FDG-PET/CT [108 cm3 (62.5-194) vs. 156 cm3 (68.8-251), p = 0.02]. When total dose was set to 50 Gy, planning on during-RT FDG-PET/CT was associated with a marginal reduction in normal tissues irradiation. When total dose was increased to 66 Gy, planning on during-RT PET yielded significantly lower doses to the spinal cord [Dmax = 44.1Gy (40.8-44.9) vs. 44.7Gy (41.5-45.0), p = 0.007] and reduced lung exposure [V20Gy = 23.2% (17.3-27) vs. 26.8% (19.7-30.2), p = 0.006]. Conclusion. This planning study suggests that adaptive RT based on target volume reduction assessed on FDG-PET/CT during treatment could facilitate dose escalation up to 66 Gy in patients with esophageal SCC. [ABSTRACT FROM AUTHOR]

Background. Fatigue is a symptom that can occur during treatment as an acute side effect but can also result in persistent fatigue as a long-term side effect or late effect. Materials and methods. We undertook a narrative review of the current literature and discuss the current evidence of assessment of fatigue and we specifically focus on the role of promoting behavioural change and focused rehabilitation to minimise these long-term effects and update the literature relating to this area from 2012 to date. Results. We suggest there are behavioural change models that can be scaled up to enable patients to manage long-term fatigue using exercise. However, from this updated review there are limitations to the current infrastructure and evidence base that will impact on the ability to do this. Conclusion. We continually need to raise awareness amongst health professionals to continue to suggest modifications to impact on fatigue at all stages of cancer treatment and into survivorship and late effects. These can range from simple brief interventions suggested in the clinic to full scale rehabilitation programmes if the correct infrastructure is available. Whichever approach is adopted we suggest exercise will be the mainstay of the treatment of fatigue in this group. [ABSTRACT FROM AUTHOR]

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive Tcell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment. [ABSTRACT FROM AUTHOR]

Background. Many cancer patients receive chemotherapy and radiotherapy their last 30 days [end of life (EOL)]. The benefit is questionable and side effects are common. The aim of this study was to investigate what characterized the patients who received chemo- and radiotherapy during EOL, knowledge that might be used to improve practice. Methods. Patients dead from cancer in 2005 and 2009 were analyzed. Data were collected from hospital medical records. When performance status (PS) was not stated, PS was estimated from other information in the records. A Glasgow Prognostic Score (GPS) of 0, 1 or 2 was assessed from blood values (CRP and albumin). A higher score is associated with a shorter prognosis. Results. In total 616 patients died in 2005; 599 in 2009. Among the 723 analyzed, median age was 71; 42% had metastases at diagnosis (synchronous metastases); 53% had PS 2 and 16% PS 3-4 at the start of last cancer therapy. GPS at the start of last cancer therapy was assessable in 70%; of these, 26% had GPS 1 and 35% GPS 2. Overall, 10% received chemotherapy and 8% radiotherapy during EOL. The proportions varied significantly between the different types of cancer. Multivariate analyses revealed that those at age < 70 years, GPS 2, no contact with our Palliative Care Unit and synchronous metastases received most chemotherapy the last 30 days. PS 3-4, GPS 2 and synchronous metastases were strongest associated with radiotherapy the last 30 days. Conclusion. Ten percent received chemotherapy and 8% radiotherapy the last 30 days of life. GPS 2 and synchronous metastases were most significantly associated with cancer therapy the last 30 days of life, indicating that in general, patients with the shortest survival time after diagnosis of cancer received more chemo- and radiotherapy during EOL than other patients. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with high-grade soft tissue sarcoma (STS) will develop pulmonary metastasis. This is the most frequent cause of death and improving treatment is warranted. Preoperative chemotherapy is used for selected patients, usually those with less favorable prognosis and mainly outside clinical trials. The predicted value of histological and radiological response to preoperative chemotherapy on outcome was the main focus for this investigation. Patients and methods. This retrospective study comprises 93 patients with metachronous lung metastasis from STS who underwent complete metastasectomy alone (n = 41) or metastasectomy following preoperative chemotherapy (n = 52). Clinical data, histological and radiological responses to chemotherapy were recorded and survival analyses performed. Results. The time from initial STS diagnosis to the appearance of metastasis was shorter in the preoperative chemotherapy group than in those treated with surgery alone (p = 0.02). However, no statistical differences in post-metastasis disease-specific survival (DSS) or progression-free survival (PFS) between the groups were demonstrated. Patients in the preoperative chemotherapy group with good (complete) histological response had improved PFS compared with poor responders (p = 0.04). Radiological partial response was an independent, favorable prognostic factor for improved PFS and DSS (p = 0.003). Conclusion. Despite having unfavorable disease characteristics, some patients may benefit from preoperative chemotherapy. Both histological and radiological responses to preoperative chemotherapy seem to be prognostic in STS patients undergoing complete pulmonary metastasectomy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 60-year-old women having the two month history of weight loss and epigastric pain. The computed tomography (CT) scan of her abdomen showed the mass in the uncinate process of pancreas and the endoscopic ultrasound confirmed the diagnosis of adenocarcinoma of pancreas. She was advised for conversion chemoradiotherapy in order to downstage the tumor. The article discusses the importance of recognizing resectable borderline in pancreatic cancer.

Background. To investigate the patterns of relapse following intensity modulated radiotherapy (IMRT) given after radical surgery for oral and oropharyngeal squamous cell cancer. Patients and methods. One hundred and two patients with oral or oropharyngeal cancer were treated with radical surgery followed by IMRT up to a mean total dose of 60 Gy between years 2001 and 2007. Thirty-nine of the patients (%) also received concomitant weekly cisplatin. Forty of the patients had oral and 62 had oropharyngeal cancer. Data on the tumour, patient and treatment factors were collected. Following therapy the patients were followed by clinical examination, endoscopy and MRI/CT at 2- to 3-months interval up to 2 years and thereafter at 6-month intervals. Results. The mean follow-up time of the patients was 55 months (range, 26-106 months). The rate for local tumour control for the whole cohort was 92.2%: 87.5% for oral cancer patients and 96.7% for oropharyngeal cancer patients. The 5-year disease specific survival was 90.2% and 5-year overall survival 84.3%. During the follow-up eight locoregional recurrences were observed, three at the primary tumour site and one at regional nodal site and four at both sites. The mean time to primary tumour recurrence was seven months (range, 2-10 months) and to nodal recurrence seven months (range, 2-12 months). Distant metastasis occurred in six (6%) patients. The factors associated with poor prognosis were the primary tumour size and tumour site with oral cancers having worse outcome. The treatment was well tolerated with no unexpected toxicities. The most frequent late toxicity was dysphagia necessitating permanent PEG in five patients. This was correlated with the advanced primary tumour size and resulting in wide tumour excision and reconstruction. Conclusions. Surgery combined with postoperative radiotherapy given as IMRT results in low level of tumour recurrence. [ABSTRACT FROM AUTHOR]

Background. We studied compliance to guidelines of curative treatments in prostate cancer (PCa), which were of special interest due to recent introduction of new treatment technologies and the fact that there existed a real choice between surgery and radiotherapy. Material and methods. We did retrospective analyses of guidelines adherence for all PCa patients receiving curative treatment at the Norwegian Radium Hospital from 2004 to 2007 after the introduction of robot-assisted prostatectomy and after-loading brachytherapy. The patients were classified into three groups in relation to guidelines: the accordance, accordance after discussion, and the deviance groups. In time Period I (2004--2005) the 2003 EAU guidelines were used and in Period II (2006--2007) in-house guidelines with minor modifications of EAU were applied. Results. During the observation period 859 patients had curative treatment for PCa, and 83% of the patients were treated according to guidelines. In the deviance group (N==146), 119 men (82%) got prostatectomy instead of radiotherapy. The reasons for deviation in the second period were age >65 years (N==70) and surgery in cases with T3 tumors (N==10), Gleason score >8 (N==13) and combinations (N==26). Deviances from guidelines in the radiotherapy group (N==27) mainly concerned patient selecting this treatment due to expectations of preserving sexuality and/or fertility. Conclusions. In spite of acceptable overall compliance to guidelines for curative PCa treatment, the proportion of non-adherence should not been overseen, in particular when new treatment technologies are introduced. Guidelines for PCa need to be monitored regularly, and the compliance to guidelines has to be assessed on a regular basis. Guidelines should avoid too strict criteria, particularly in relation to age. [ABSTRACT FROM AUTHOR]

Studies comparing the safety and tolerability of biological therapies for psoriasis in the long-term and in daily clinical practice are lacking. Most published studies are of selected patients with short-term (3-6 months) followup. We performed a retrospective cohort study of 103 patients in order to describe the frequency and the clinical features of adverse events, and to evaluate and compare the tolerability and safety of efalizumab, etanercept, infliximab, and adalimumab in clinical practice. A total of 136 courses of biological therapies were administered, with a mean duration of 16 months/patient; 55 patients received efalizumab, 45 etanercept, 33 infliximab, and 3 adalimumab. Inifiximab had an incidence rate ratio of suspension due to severe adverse events 5.9 times (95% confidence interval (95% CI) 1.9-18, p<0.001) higher than etanercept and 9.8 times (95% CI 3.2-30.1, p<0.001) higher than efalizumab. Safety profiles for efalizumab and etanercept were more favourable than for infliximab. Concerning tolerability, we found that more patients responded to infliximab, but long-term tolerability was higher for both efalizumab and etanercept due to the better safety profile and a higher compliance to therapy. [ABSTRACT FROM AUTHOR]

Purpose/background. Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods. One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ2 test (p = 0.44). Conclusions. Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort. [ABSTRACT FROM AUTHOR]

Introduction. Palliative cancer care in acute hospitals is scarcely studied. We therefore described and compared symptoms, care needs and types of cancer sites in 2002 compared to 2007 and analysed the relationships between these factors. Methods. The study was population-based with a cross-sectional design and was carried out in medical, surgical and oncology wards in two acute care hospitals with no advanced palliative home care service. In 2002, 82 one-day-inventories were done (1 352 patients) compared to 142 one-day-inventories in 2007 (2 972 patients). Symptoms, care needs and cancer site were registered according to a questionnaire. Multiple logistic regression models were used to analyse associations between symptoms, care needs and cancer site. Results. The proportion of palliative cancer patients had decreased during a five year period (14% vs. 11%, p<0.01). The patients were older in 2007 (74 vs. 70 years, p<0.001) and had more symptoms and care needs per patient (2.6 vs. 1.6, p<0.001). The most common symptoms were pain and deterioration and the most common cancer sites were prostate and colorectal cancer in both samples. Associations between symptoms, care needs and cancer site were mostly weak. Deterioration was associated with colorectal cancer, whereas pain was not associated with any specific cancer site. In haematological malignancies there was a high occurrence of infections and a high need of blood transfusions and infusions. Stomach/oesophagus cancers were significantly associated with nausea, nutritional problems and need of infusions while unknown primary malignancies were associated with abdominal surgery and infusions. Discussion. Although we do not know all the causes for hospitalization, this study indicates that more focus should be on the symptoms instead of the specific cancer diagnosis. The findings also indicate that many palliative cancer patients’ problems would be suitable for advanced palliative home care instead of acute hospital care. [ABSTRACT FROM AUTHOR]

Background. The benefit of adjuvant therapy for resected small bowel adenocarcinoma has not been proven. We undertook a retrospective analysis to evaluate the benefit of adjuvant therapy in a clearly defined patient population with curatively resected small bowel adenocarcinoma. Material and methods. We identified 54 patients with small bowel adenocarcinoma who underwent margin-negative surgical resection and were evaluated after surgery at the University of Texas, M. D. Anderson Cancer Center between 1990 and 2008. Disease-free survival (DFS) and overall survival (OS) were estimated. Results. Median age was 55 years and primary tumor site was duodenum in 67%, jejunum in 20%, and ileum in 13%. Thirty patients (56%) received adjuvant therapy consisting of systemic chemotherapy with or without radiation in 28 and radiation alone in two. Patients who received adjuvant therapy had significantly higher tumor stage and rate of lymph node involvement. Five-year DFS and OS did not differ between treatment groups. In multivariate analysis, the use of adjuvant therapy was associated with improved DFS (HR 0.27; 95% CI 0.07–0.98, P = 0.05) but not OS (HR 0.47; 95% CI 0.13–1.62, P = 0.23). In patients with a high risk of relapse (defined as a lymph node ratio ≥10%), adjuvant therapy appeared to improve OS, P = 0.04, but not DFS, P = 0.15. Discussion. The use of adjuvant therapy for curatively resected small bowel adenocarcinoma was associated with an improvement in DFS. This finding strongly supports further investigation of adjuvant chemotherapy in this tumor type. [ABSTRACT FROM AUTHOR]

Background. Treatment of patients with carcinoma of unknown primary site (CUP) remains a challenge, and no effective second-line treatment has been identified. In CUP patients who are non-responsive or relapse early after first-line platinum/taxane-based regimens, it is likely that gastrointestinal (GI) tract tumours may be overrepresented. These patients could be candidates for GI tract-directed therapy. We here report the results obtained with oxaliplatin and capecitabine as second-line therapy in 25 recurrent/refractory CUP patients following first-line treatment with paclitaxel, cisplatin and gemcitabine. Patients and methods. Patients received capecitabine orally (1000 mg/m2) twice daily, days 1–14, and oxaliplatin (130 mg/m2) intravenously on day 1 in a three-week schedule. Results. Twenty-five CUP patients received a median of three cycles of capecitabine and oxaliplatin as second-line treatment. Histopathological assessments suggested the primary site to be of GI tract origin in the majority of the patients (76%). We found an objective response rate of 13%, a median progression-free survival and overall survival rate of 2.3 and 3.9 months, respectively, and 32% of patients alive at one year after initiation of second-line therapy. The regimen was well tolerated by most patients. Conclusions. This study, demonstrates that there is still a significant need for improved second-line therapy in CUP patients. [ABSTRACT FROM AUTHOR]

Photodynamic therapy is a potentially advantageous treatment for non-melanoma skin cancers. We evaluated the clinical response, recurrence and adverse events of photodynamic therapy for in situ extramammary Paget's disease in 14 male and 3 female Chinese patients with 21 lesions. Topical 20% 5-aminolevulinic acid was applied for 6 h. Each lesion was irradiated with 633 nm red light three times, 1 week apart, at a total dose of 339 J/cm2, followed by three assessments at 6, 12 and 24 months. Overall complete response (CR) rates were 52.4%, 42.9%, and 33.3% at 6, 12 and 24 months, respectively. The CR rate was significantly higher in scrotal lesions (66.6%) than in non-scrotal lesions (8.3%). The overall recurrence rate was 50%. The highest CR rate was for the lesions ?8 cm (0%). Most adverse events were well tolerated. In conclusion, photodynamic therapy for extramammary Paget's disease is not recommended as the first option except for scrotal cases or lesions

Aim. The aim of this study was to explore the clinical value of gemcitabine combined with capecitabine (GC) in heavily pre-treated patients with metastatic breast cancer. Material and methods. All patients had failed anthracyclines and taxanes. In 14 patients (41%), more than two metastatic sites were diagnosed with bone (68%) and liver (62%) being the most prominent. Gemcitabine (1 250 mg/m2, d1+8) and capecitabine (800 mg/m2 twice daily, d1-14) were administered according to a 3-week schedule. The majority of patients received GC as 3rd or 4th line chemotherapy for metastatic disease. Laboratory tests were done on day 1+8 in cycles. Subjective toxicity was recorded according to the NCI-CTC v. 2.0 criteria. Tumour evaluations were done every 12th week according to the RECIST criteria. The primary objective was to investigate time to progression. Secondary objectives were response rate with special focus on the proportion of patients achieving PR or SD of at least three months, toxicity and survival. Results. A total of 34 patients were enrolled. All subjects are eligible for toxicity, response and time to event analyses. Treatment was given until progressive disease, severe toxicity or until the patient wanted to withdraw. The Kaplan-Meier median time to progression was estimated to 4.3 months and the overall survival time to 13.7 months. Partial response was noted in 12 of 29 evaluable patients (41%). The best outcome amongst remaining patients was stable disease in nine (31%) or tumour progression in eight (28%). A delay of disease progression of more than three months was noted in 53% of the study population. The main side effect was granulocytopenia with 44% and 15% of patients suffering from grade 3 or grade 4 events respectively however, no neutropenic infections were observed. Pre-dominant grade 3 subjective toxicities were: fatigue (21% of patients) and hand-foot syndrome (15% of patients). Discussions. We investigated the value of the GC combination as a treatment for late stage breast cancer patients. Tumour progression was delayed and the treatment was well tolerated. We believe that the GC therapy can achieve meaningful palliation. [ABSTRACT FROM AUTHOR]

Background. Signet-ring cell carcinoma (SRCC) is an uncommon tumor entity in rectal cancer, often considered to be resistant to non-surgical therapy. In locally advanced primary or recurrent rectal cancer, diagnostic information from magnetic resonance imaging (MRI) is considered superior in planning the optimal treatment strategy, which usually includes preoperative radiotherapy. The recognition of MRI features that correlate with the radiation response might ultimately be used to select patients for tailored treatment and, in addition, avoid potentially toxic therapy in non-responding patients. Material and methods. In a cohort of 120 rectal cancer patients who had received preoperative radiotherapy (50 Gy in 2 Gy fractions), six patients were noted to have SRCC tumor differentiation. Initial diagnostic MRI examination included assessment of local T- and N-stage and tumor morphology. Histological tumor response was subsequently assessed in the resected specimens, and postoperative follow-up data was compiled until disease recurrence. Results. Following the preoperative radiotherapy, two distinctly different histological responses – complete response (ypT0N0) or no response – were observed. Extensive mesorectal lymph node metastasis (N2 disease) at the pretreatment MRI examination was unambiguously associated with lack of response and rapid development of disseminated disease. Importantly, patients with complete response have been observed for 23–52 months postoperatively without evidence of recurrent disease. Discussion. Our review may suggest that patients with locally advanced growth of rectal SRCC, despite poorer outcome when compared to patients with conventional-type rectal adenocarcinoma, when presenting limited lymph node disease should be offered preoperative radiotherapy in a tentatively curative setting. [ABSTRACT FROM AUTHOR]

Purpose. Recently, Elekta has supplied volumetric modulated arc therapy (VMAT) in which multi-leaf collimator (MLC) shape, jaw position, collimator angle, and gantry speed vary continuously during gantry rotation. A quality assurance procedure for VMAT delivery is described. Methods and materials. A single-arc VMAT plan with 73 control points (CPs) and 5-degree gantry angle spacing for a prostate cancer patient has been created by ERGO + + treatment planning system (TPS), where MLC shapes are given by anatomic relationship between a target and organs at risk and the monitor unit for each CP is optimized based on given dose prescriptions. Actual leaf and jaw positions, gantry angles and dose rates during prostate VMAT delivery were recorded in every 0.25 seconds, and the errors between planned and actual values were evaluated. The dose re-calculation using these recorded data has been performed and compared with the original TPS plan using the gamma index. Results. Typical peak errors of gantry angles, leaf positions, and jaw positions were 3 degrees, 0.6 mm, and 1 mm, respectively. The dose distribution obtained by the TPS plan and the recalculated one agreed well under 2%-2 mm gamma index criteria. Conclusions. Quality assurance for prostate VMAT delivery has been performed with a satisfied result. [ABSTRACT FROM AUTHOR]

Introduction. The aim of this retrospective analysis was to analyze the results of conventional radical radiotherapy in the treatment of oropharyngeal cancer and to identify pre-treatment and treatment-related prognostic factors for outcome. Material and methods. The records of 627 patients with oropharyngeal cancer treated with radical radiotherapy with conventional techniques were analyzed. Results. The median age was 56 years. History of tobacco abuse was present in 80.5%. Eighty six percent had stage III or IV disease. Radical radiotherapy alone was the treatment modality for 71.2% and concomitant or neoadjuvant chemotherapy was used in 28.8%. The 3-year local control (LC), loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) was 49%, 40.6%, 38.9% and 36.1% respectively. The 3-year DFS rates were 80.3% for stage I, 65.8% for stage II, 46.1% for stage III and 25.2% for stage IV disease. Multivariate analysis was performed for prognostic factors. Prior history of tobacco abuse was an independent prognostic factor for both DFS and LRC. Karnofsky Performance Score (KPS) < 80, higher nodal stage, lower total radiotherapy dose (<66 Gy) in those receiving > 60 Gy, and overall treatment time > 50 days were other independent prognostic factors for inferior DFS and LRC. KPS < 80, higher T stage, higher nodal stage, RT dose < 66 Gy and longer overall treatment time (>50 days) were independent prognostic factors for poorer local control. Conclusions. Several patient-, disease- and treatment-related variables independently affect survival outcomes after radical radiotherapy for oropharyngeal cancer. Oropharyngeal cancers in those without a history of tobacco abuse may be biologically different and more amenable to cure with radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction. Erythropoiesis-stimulating agents (ESAs) are used in cancer therapy to reverse anaemia. It has been suggested that ESAs might improve treatment outcome by reducing tumour hypoxia, but ESAs might also increase tumour growth. In this work, the effect of recombinant human erythropoietin (rHuEpo) β was investigated on a human head and neck squamous carcinoma cell (HNSCC) line in vitro. The cell line was previously growth stimulated in combination with surgery in a xenograft model and the investigation was initiated to see if rHuEpo directly affects the tumour cell line, alone or in combination with cell stress, or if the in vivo effect should be attributed to secondary effects. Material and methods. The cell line LU-HNSCC-7 was grown in vitro and treated with rHuEpo alone or in combination with radiation, cisplatin, hypoxia or tumour extracts. The expression of the Epo receptor (EpoR) was investigated by western blotting after one- and two-dimensional electrophoresis, RT-PCR and through analysis of the effect on EpoR signalling. Results. The cell line was shown not to express EpoR. Furthermore, it was only possible to detect a minor effect on cell growth (1.4 times over control, p < 0.001) under specific conditions and at supra-pharmacological concentrations of rHuEpo β. No effect was detected on cell migration. None of the cell stressing treatments could enhance the minor growth stimulatory effect of rHuEpo β. Discussion. The conclusion is that rHuEpo β does not stimulate tumour growth of the investigated cell line through a direct interaction with tumour cells. We hypothesise that interactions with stromal cells and the stimulation of wound healing responses might, at least partly, explain the negative effects of ESA administration during cancer treatment. We propose that EpoR expression in HNSCC tumour cells might not be a good marker for prediction of ESA induced worsening of outcomes after cancer treatment. [ABSTRACT FROM AUTHOR]

Background. The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival. Patients and methods. At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.Results. The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s. Conclusions. Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients. [ABSTRACT FROM AUTHOR]

Introduction. The pattern of failure (POF) after first-line systemic therapy in advanced non-small cell lung cancer (NSCLC) is unknown. We evaluate the POF in this setting to estimate the potential value of consolidative stereotactic body radiation therapy (SBRT). Materials and methods. The records of consecutive NSCLC patients presenting to the University of Colorado, Denver (UCD) between January 2005 and June 2008 were reviewed. Patients with measurable advanced stage NSCLC who received first-line systemic therapy and follow-up at UCD were eligible. In these patients, sites of disease at maximal response were evaluated for theoretical SBRT eligibility, based on institutional criteria. All patients were followed to extracranial progression. The POF was categorized as local (L) for lesions known prior to treatment or distant (D) for new lesions. Results. Among 387 consecutive lung cancer patients (all stages), 64 met the eligibility criteria and 34 were SBRT-eligible. Among all eligible patients, first extra-cranial progression was L-only in 64%, D-only in 9% and L + D in 27%. Among SBRT-eligible patients, POF was L-only in 68%, D-only in 14% and L + D in 18%. In SBRT-eligible patients, time to first progression was 3.0 months in those with L-only failure versus 5.7 month in those with any D failure (HR 0.44; 95% CI 0.22-0.90). Conclusions. The predominant POF in patients with advanced NSCLC after first-line systemic therapy is local-only. The current analysis suggests that SBRT could improve time to progression in a substantial proportion of patients. The estimated increase in time to progression using this approach would be approximately 3 months. [ABSTRACT FROM AUTHOR]