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PURPOSE To identify and describe experiences of patients with colorectal cancer (CRC) who have neurotoxic side effects early in the oxaliplatin treatment period, and how neurotoxicity affects their daily lives. PARTICIPANTS A SETTING 10 patients with stage II-III CRC were included. All were treated with adjuvant oxaliplatin postoperatively and assessed neurotoxicity via a platform-independent mobile phone-based system. Patients were recruited from two hospitals in southern Sweden from November 2013 to August 2014. METHODOLOGIC APPROACH Qualitative interview study conducted through open-ended, face-to-face, qualitative interviews. Thematic analysis was used. FINDINGS A main theme was identified. IMPLICATIONS FOR NURSING Nurses have an obligation to communicate the importance of early detection of neurotoxicity. Mobile phone technology seems to be a valuable tool for monitoring patient-reported neurotoxicity to improve communication and supportive care.

Purpose The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. Patients and Methods Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. Results Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. Conclusion Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

A Swedish national care programme has provided guidelines for staging, treatment and follow-up of all patients with Hodgkin's disease (HD) since 1985. Between January 1985 and December 1992, 920 patients were reported and followed prospectively. Of a total of 533 patients with stage I and II disease, 484 presented with supradiaphragmatic HD and 49 (9%) with infradiaphragmatic HD. The median follow-up time was 4.3 yr (3.3-10 yr). Significant differences in average age (45 +/- 21 yr and 55 +/- 19 yr), male:female ratio (1.1:1 and 2.8:1) and B-symptoms (25% and 47%) were observed in patients with supra- and infradiaphragmatic HD, respectively. Forty-six patients with infradiaphragmatic HD were treated with a curative intention and 40 (87%) achieved a complete response. Eleven (28%) of the 40 patients have recurred and 8 patients have died of HD. Complete response rates and recurrence frequencies did not differ from those observed in patients with supradiaphragmatic HD. Mortality was, however, significantly higher (p = 0.001) in the infradiaphragmatic group; this was due mainly to poorer effects of salvage treatment in a elderly population. In this population-based study, patients with peripheral disease in stage IA respond well to inverted Y irradiation alone, whereas it appears to be important to give stage II patients chemotherapy or a combined modality treatment in order to avoid unacceptably high recurrence rates.

Udgivelsesdato: 2008-Jun BACKGROUND: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. PATIENTS AND METHODS: A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. CONCLUSION: XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.

Udgivelsesdato: 2008-May BACKGROUND: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m(2) on day 1, 5-FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5-FU bolus 400 mg/m(2) and infused 5-FU 600 mg/m(2) on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. PATIENTS AND METHODS: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). RESULTS: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. CONCLUSIONS: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

PURPOSE: The purpose of this study was to explore the experiences of oxaliplatin-induced neurotoxic side effects among patients with colorectal cancer (CRC) and how these side effects influenced their daily lives over time. METHODS: To assess neurotoxic side effects, ten patients were repeatedly interviewed. The patients were recruited from two hospitals in south of Sweden, had stage II-III CRC, and had been treated with adjuvant oxaliplatin postoperatively, from November 2013 to October 2015. They had received FOLFOX and XELOX, with a mean total dose of 791 mg oxaliplatin. After completed chemotherapy, at 3, 6, and 12 months into the post-treatment phase, 25 interviews were conducted and thematic analysis was used according to Braun and Clarke. RESULTS: Oxaliplatin-induced neurotoxicity affects patients in several ways in the long term. Four themes were identified: Expectation of cure, Dubiety, Normalization, and Learn to live with neurotoxicity. The findings of this study describe the trajectory of neurotoxicity and its impact on these patients' life situation. The findings confirmed that neurotoxicity is multi-faceted and that the experience of it changes over time. CONCLUSION: The desire to survive stimulates adaptations and strategies to manage daily life, and patients learn to live with the neurotoxic side effects. This study provides evidence that these patients need individual attention and support during the trajectory of neurotoxic side effects. Current care provision is inadequate due to a lack of knowledge of the ways in which neurotoxicity impacts the patient's daily life. This study provides insights that could be used to develop a more person-centered care. Funding agencies:We thank all patients for their participation in this study. We also thank the Swedish Cancer Society, the Department of Oncology and Surgery, Linkoping University Hospital, and the Division of Nursing Science at the Department of Medical and Health Sciences for the financial support. Further thanks go to all the health professionals in the oncology clinics who were involved in the study in different ways.

The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended.For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied.From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results.XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules.

An increasing incidence of testicular cancer has been reported from several western countries during the last decades. According to current hypothesis testicular cancer is initiated during the foetal period and exposure to endocrine disruptors such as some persistent organic pollutants has been of concern. We have previously reported the results for concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene (pp'-DDE), hexachlorobenzene (HCB) and chlordanes in 58 cases with testicular cancer, 61 age-matched controls and 44 case mothers and 45 control mothers. In that report, significant increase of odds ratio (OR) was found for sum of PCBs, HCB, trans- and cis-nonachlordane in case mothers. These data have now been further analysed for 37 congeners of PCBs. No significant differences were found among cases and controls. However, case mothers had significantly increased concentrations of a number of PCB congeners. A priori decided grouping of PCBs yielded for oestrogenic PCBs OR = 2.4, 95% confidence interval (CI) = 0.95-6.0, enzyme-inducing PCBsOR = 2.6, 95% CI = 1.03-6.5 and toxic equivalents (TEQ) yielded OR = 3.3, 95% CI = 1.3-8.4. These data further elucidate the role of foetal exposure to different PCB congeners in the aetiology of testicular cancer.

The aim of the study was to evaluate the effect of palliative chemotherapy on soft tissue sarcomas given outside controlled trials. Therapy and response rates of 77 patients with non-resectable sarcoma treated with different regimens between 1991 and 2000 were reviewed. Thirty-six patients were treated with first-line chemotherapy comprising cyclophosphamide+vincristine+doxorubicin+dacarbazine (CYVADIC), with a response rate of 28% (median response duration 5.5 months). Etoposide and ifosfamide (IVP, or VIG, which also includes granulocyte colony-stimulating factor (G-CSF)) were used in the treatment of 18 patients. The response rate was 22% (median response duration 4.5 months); Nineteen patients were treated with doxorubicin+ifosfamide and one patient responded. Four patients received other first-line treatments. Thirty-eight patients were given second-line chemotherapy and 4 (10%) patients responded. Thirteen patients were given third-line treatment and 5 patients received fourth-line treatment, but without any response. Disease progression was the dominant reason for discontinuation of therapy. The response rate in the present study was lower than the best published results, probably due to the fact that our soft tissue sarcoma patient material was unselected. Treatment with CYVADIC yields at least as high a response rate as the more recently described doxorubicin+ifosfamide combination, but third- and fourth-line therapy is not beneficial. Clinical trials with more active drugs are needed, as are more predictive and prognostic tests and a better selection of patient groups suited for different treatment options for soft tissue sarcomas.

An increasing incidence of testicular cancer has been reported from several countries in the Western world during the last decades. According to current hypothesis, testicular cancer is initiated during the fetal period, and exposure to endocrine disruptors, i.e., xenoestrogens, has been of concern. In this investigation we studied the concentrations of the sum of 38 polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyl-dichloroethylene, hexachlorobenzene (HCB), and chlordanes, in 61 cases with testicular cancer and 58 age-matched controls. Furthermore, case and control mothers were also asked to participate, and 44 case mothers and 45 control mothers agreed. They were of similar age. In cases only the concentration on lipid basis of cis-nonachlordane was significantly increased, whereas case mothers showed significantly increased concentrations of the sum of PCBs, HCB, trans- and cis-nonachlordane, and the sum of chlordanes. Among case mothers the sum of PCBs yielded an odds ratio (OR) of 3.8; 95% confidence interval (CI), 1.4-10 was calculated using the median concentration for the control mothers as cutoff value. For HCB, OR = 4.4 (95% CI, 1.7-12); for trans-nonachlordane, OR = 4.1 (95% CI, 1.5-11); for cis-nonachlordane, OR = 3.1 (95% CI, 1.2-7.8); and for sum of chlordanes, OR = 1.9 (95% CI, 0.7-5.0). No consistent different risk pattern was found for seminoma or nonseminoma testicular cancer.

The study aimed to describe and follow a 2 year cohort of colon cancer patients with Stage IV disease from presentation to long-term outcome.The records of 177 colon cancer patients diagnosed in southeast Sweden during 2009-2010 with disseminated disease at presentation were reviewed retrospectively.The patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty-one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231 days (emergency cases included, median 12 days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1-year survival was 46%.Patients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.

The empirical data of this study were gathered in the form of audio-taped recordings of dialogues between 21 patients, who had had operations for testicular cancer and three physicians during follow-up consultations. The aim is to inquire into how routine practices affect the goals of checking up the medical conditions and providing patients with reassurance, and how practices affect the treatment of sensitive topics and the patients’ possibilities of bringing up their own problems are affected. The results show that the routines built up by the medical care programme are used as recurrent opportunities for the parties to confirm that the situation is under control and as resources when they talk about the sensitive topics of sexuality and fertility. How the routinization affected the patients’ possibilities of bringing up their own problems cannot be fully determined. Of the 50 initiatives by patients to present their problems, only nine did so solely on their own initiative.

Summary Background In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. Methods Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300–350 mg/m 2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. Findings 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58·8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0·0001), with 36·2% 1-year survival in the irinotecan group versus 13·8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0·001). Survival without performance-status deterioration (p=0·0001), without weight loss of more than 5% (p=0·018), and pain-free survival (p=0·003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. Interpretation Our study shows that despite the sideeffects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.

Patients with colorectal cancer (CRC) can have chemotherapy with oxaliplatin postoperatively. Oxaliplatin can cause acute and chronic neurotoxicity. It is important to be aware of neurotoxic side effects so they can be documented and action taken at an early stage. The study aimed to identify and explore neurotoxic side effects documented in the medical records of patients with colorectal cancer treated with oxaliplatin-based adjuvant chemotherapy. Data in this study were medical records; presenting documentation about patients treated at the University Hospital in the south of Sweden between 2009 and 2010. A summative content analysis approach was used to explore the neurotoxic side effects. Identification and quantification of the content of medical records were carried out by using a study-specific protocol. “Cold sensitivity” and “tingling in the hands” were the most frequently documented neurotoxicity-related terms in the medical records. This identification was followed by interpretation. Three categories were identified in the interpretive part of the study: acute, chronic, and degree of neurotoxicity. The results show the importance of awareness of neurotoxic side effects so that they can be documented and action taken at an early stage. The documentation could be more reliable if patient-reported structured measurements were used, combined with free descriptions in the medical records. Being able to follow the progression of the symptoms during and after treatment would improve patient’s safety and also quality of life. The protocol that we developed and used in this review of medical records may be helpful to structure the documentation in the electronic system for documentation of neurotoxicity side effects.

OBJECTIVE. In patients with colon cancer, high age and comorbidity is common. In this population-based retrospective study we have investigated causes of death and the influence of urgent operation, and gender on survival. MATERIAL AND METHODS. Medical records of 413 patients with verified colon cancer were reviewed. The diagnosis was made during 2000-2006 and operation was performed in 385 patients (93%). RESULTS. The overall 5-year survival after surgery was 48.3%. At the end of the follow-up, 128 patients (54.9%) had verified colon cancer when they died but 105 patients (45.1%) had no signs of colon cancer. Their 5-year survival was 5.5% and 41.9%, respectively (p < 0.0001). Median survival time was significantly shorter after urgent compared with elective admittance, 20.7 months versus 77.9 months, and the 5-year survival 32.4% versus 57.9% (p = 0.0001). The tumor stage at operation was more favorable in patients dying with no signs of colon cancer than in those dying with cancer regarding stage I-II (66.7% versus 16.4%), and stage IV (1.0% versus 53.1%), but not regarding stage III (30.5% versus 29.7%). The overall survival in women who were operated was longer than in men (p = 0.045) as well as survival after elective admittance (p = 0.013). CONCLUSION. After a median follow-up of 56.1 months almost half of the patients who were dead had died from other causes than colon cancer. Ten percent of those patients had an incorrectly reported diagnosis of colon cancer as cause of death. Urgent admittance was associated with reduced survival time. The median survival time was longer in women than in men.

Background : Colorectal cancer is one of the most common types of tumour in the world. Treatment side effects, together with the tumour symptoms, can result in a ‘symptom burden’. To understand the patient’s burden during chemotherapy treatment and plan effective symptom relief there is a need for more knowledge about the experience of symptoms from the patients’ perspective. Objectives : The study was designed to qualitatively identify and describe the most common symptoms among patients treated for colorectal cancer, and discover whether there are barriers to reporting symptoms. Methods : Thirteen Swedish patients diagnosed with colorectal cancer and treated with chemotherapy were interviewed face-to-face. The interviews were audio-taped and transcribed verbatim. The transcripts were analysed by following the principles of qualitative content analysis. Results : Nine symptoms/forms of distress were identified. Those most frequently expressed were fatigue, changed bowel habits, and affected mental well-being, closely followed by nausea, loss of appetite and neurological problems. Of particular note were the affected mental well-being, the magnitude of the neurological problems described, the symptoms related to skin and mucous membrane problems, and the reports of distressing pain. Barriers to symptom control were only expressed by the patients in passing and very vaguely. Conclusion : This study confirms other reports on most common symptoms in colorectal cancer. It also highlights the early onset of symptoms and provides data on less well-studied issues that warrant further study, namely affected mental well-being, the magnitude of the neurological problems and symptoms related to the skin and mucous membranes. Nurses need to be sensitive to the patients’ need presented and not only noting symptoms/distresses they have guidelines for.

Implantable injection port systems are safe and convenient for long-term venous access. The present investigation comprises nurses' and patients' evaluation of three different types of devices; Port-A-Cath (16.0 g), Cordis Miniport (3.8 g) for implantation in the chest wall and the PAS Port system (5.6 g) for implantation in the forearm. The devices were implanted for chemotherapy. Eighty patients and 17 nurses answered a questionnaire regarding their experience with the devices. Overall, the systems functioned well and were helpful for both patients and nurses. In the patient study few significant differences emerged. Nurses noted that the PAS Port system was more difficult to withdraw blood from (P < 0.001) and its infusion flow capacity was inferior to the two ports in the chest wall (P < 0.001). Port-A-Cath was judged to be the easiest system for needle insertion and the needle position was felt to be more secure (P < 0.001). Fourteen of the 17 nurses preferred Cordis Miniport for cosmetic reasons (P < 0.001). All devices functioned well. The differences in shape, size and site of implantation allow an optimum port selection for each patient. The replies in this study expressed the need for educational programmes in order to spread the injection port concept further.

Background The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer. Results Paraffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% CI, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% CI, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen. Conclusions PINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.

Purpose. Continuous minor steps of improvement in the management of breast cancer have resulted in decreased mortality rates during the last decades. The aim of this study was to compare the clinical outcome of patients with stage I breast cancer diagnosed during two time periods that differed with respect to adjuvant systemic therapy. Material and methods. The studied population consisted of all women 60 years of age, who were diagnosed breast cancer stage I between 1986 and 1999 in south-east Sweden, a total of 1 407 cases. The cohort was divided into two groups based on the management programmes of 1986 and 1992, hereafter referred to as Period 1 and Period 2. Before 1992 the only adjuvant systemic therapy recommended was tamoxifen for hormone receptor positive patients aged 50 years or older. During Period 2 the use of adjuvant treatment was extended to younger patients at high risk, identified by a high tumour S-phase fraction, with either hormonal or cytotoxic treatment. Results. The estimated distant recurrence-free survival rate was significantly higher during Period 2 than during Period 1 (p = 0.008). Subgroup analysis showed that the most evident reduction of distant recurrence risk was among hormone receptor-negative patients (HR = 0.58, 95% CI 0.31-1.09, p = 0.09) and among patients with a high tumour S-phase fraction (HR = 0.53, 0.30-0.93, p = 0.028). The risk reduction between the periods was still statistically significant in multivariate analysis when adjusting for different tumour characteristics and treatment modalities, indicating an influence of other factors not controlled for. One such factor may be the duration of tamoxifen treatment, which likely was more frequently five years during Period 2 than during Period 1. Conclusions. We conclude that the causes of the increase in distant recurrence free survival for women with breast cancer stage I are complex. The results support though that high-risk subgroups of stage I breast cancer patients did benefit from increased use of systemic therapy as a consequence of an updated management programme. This is an electronic version of an article published in: Patrik Johansson, Helena Fohlin, Lars-Gunnar Arnesson, Monika Dufmats, Kerstin Nordenskjoeld, Bo Nordenskjöld and Olle Stål, Improved survival for women with stage I breast cancer in south-east Sweden: A comparison between two time periods before and after increased use of adjuvant systemic therapy, 2009, ACTA ONCOLOGICA, (48), 4, 504-513. ACTA ONCOLOGICA is available online at informaworldTM: http://dx.doi.org/10.1080/02841860902718754 Copyright: Taylor & Francis http://www.tandf.co.uk/journals/default.aspGroup Author(s):The South-East Sweden Breast Cancer Study GroupAnnika Malmström, Linköping University

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.

The widening gap between available resources and increasing possibilities to diagnose and treat different medical conditions has resulted in new attention to priority setting. The issue is complicated and harbours several obstacles because of different valuations concerning the needs of patient groups, the true results (patient benefit) of medical actions, and also important ethical considerations. Earlier attempts have been unsuccessful in introducing a prioritization milieu into the medical profession, probably due to vague requests for an open and sharp prioritization process. With a sharpened competition of allocating resources for different medical actions, the medical profession of the cancer sector needs to have a tool for explaining consequences for the different cancer patient groups and what is achieved by the cancer treatments and the care. A model for ranking lists consisting of pairs of patient conditions and medical actions is presented, and the principle for using these lists for priority setting in medical society is discussed.

The urinary excretion of the hydroxylated DNA base 8-hydroxydeoxyguanosine (8-OHdG) and the lipid peroxidation product malondialdehyde (MDA) was monitored in 11 patients with hematological malignancies undergoing total body irradiation and high-dose chemotherapy preceding bone marrow transplantation. Nine patients showed a prompt increase in urinary 8-OHdG (8-25 times the initial baseline level) on days 0-7 after irradiation onset; the excretion then decreased during the aplastic period and increased again when engraftment took place (in 7 patients). A significant positive correlation was found between urinary 8-OHdG and whole blood leukocyte count, both on day 5 (p =.04, r =.72) and on day 22 (p =.009, r =.80) after irradiation onset. One patient who lacked the first peak of 8-OHdG excretion showed low blood leukocyte counts (less than 2 x 10(9)/l) before therapy onset; this patient, however, later had a successful engraftment and then also showed considerable increases in both 8-OHdG excretion and leukocyte count. These observations suggest leukocytes play a part in the excretion of 8-OHdG after conditioning therapy preceding bone marrow transplantation. As opposed to the biphasic 8-OHdG excretion, the excretion of MDA showed a single peak appearing on days 11-19 after radiochemotherapy onset, i.e., during the period in which the patients suffered from cytopenia, mucositis, and other side effects of the treatment. It is suggested, therefore, that these clinical manifestations are associated with increased lipid peroxidation. Altogether, these findings illustrate the utility of serial urinary samples for monitoring oxidative stress due to conditioning therapy in clinical practice. They also demonstrate that different oxidative stress markers may behave quite differently regarding their appearance in the urine after whole-body oxidative stress.

The aim of the study was to evaluate the effect of palliative chemotherapy on soft tissue sarcomas given outside controlled trials. Therapy and response rates of 77 patients with non-resectable sarcoma treated with different regimens between 1991 and 2000 were reviewed. Thirty-six patients were treated with first-line chemotherapy comprising cyclophosphamide+vincristine+doxorubicin+dacarbazine (CYVADIC), with a response rate of 28% (median response duration 5.5 months). Etoposide and ifosfamide (IVP, or VIG, which also includes granulocyte colony-stimulating factor (G-CSF)) were used in the treatment of 18 patients. The response rate was 22% (median response duration 4.5 months); Nineteen patients were treated with doxorubicin+ifosfamide and one patient responded. Four patients received other first-line treatments. Thirty-eight patients were given second-line chemotherapy and 4 (10%) patients responded. Thirteen patients were given third-line treatment and 5 patients received fourth-line treatment, but without any response. Disease progression was the dominant reason for discontinuation of therapy. The response rate in the present study was lower than the best published results, probably due to the fact that our soft tissue sarcoma patient material was unselected. Treatment with CYVADIC yields at least as high a response rate as the more recently described doxorubicin+ifosfamide combination, but third- and fourth-line therapy is not beneficial. Clinical trials with more active drugs are needed, as are more predictive and prognostic tests and a better selection of patient groups suited for different treatment options for soft tissue sarcomas.

The aim of this study was to identify patients in need of palliative care in 11 different care units with a total of 256 beds at Linkoping University Hospital and to look at their overall situation with respect to assessed symptom control and quality of life. There were 46 patients fulfilling the two criteria of incurable cancer and need for palliative care, and each was assessed with the aid of a questionnaire (five oral questions on life situation) and a single visual analogue scale (VAS) about their overall quality of life (QoL). Each patient also assessed him- or herself on the Edmonton Symptom Assessment Scale (ESAS). Total ESAS scores ranged from 20 to 639 mm (median 211). Median VAS scores (100 mm = greatest symptom severity) were as follows: nausea 6 mm, pain 9 mm, anxiety 17 mm, depression 18 mm, drowsiness 35 mm, activity 38 mm, appetite 45 mm, and sensation of well-being 46 mm. The median score for QoL was 47 and correlated well with the total ESAS score. Thirty-seven patients answered the open question "What in your current situation troubles you the most?". Seven patients answered "nothing", and 10 said "the present symptoms". Twenty patients had different concerns (existential, social, and psychological). The low number of hospitalised patients found reflects a well-functioning hospital-based home-care unit. Reduced appetite, sensation of well-being and activity were dominant, while pain and nausea were less intense. The simple QoL-VAS seemed to be comparable to ESAS, which is more useful for assessing each single symptom. The non-physical dimensions need more attention in the future in order to achieve totally satisfactory palliative care.

Purpose: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). Patients and methods: Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status less than or equal to 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed greater than or equal to 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m(2), i.v., day 1, alternating with leucovorin 20 mg/m(2) i.v. and 5-FU 425 mg/m(2), i.v, daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. Results: Thirty-three patients (28 chemotherapy-naive and five with prior adjuvant treatment completed >1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. Conclusions: The alternating schedule of CPT-11 350 mg/m(2) with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.

Totally implantable portal systems are widely used for long-term central venous access. A new venous portal system inserted via the brachial veins (P.A.S. Port™ system, Pharmacia Deltec Inc, U.S.A.) was studied in five centres. From January 1988 through May 1989 61 systems were implanted. Fifty-two patients had malignant diseases. Nine cases had non-malignant disorders. The portals were implanted subcutaneously in the fore-arm and catheterization was done percutaneously (46) or by cutdown-technique (15) under local anesthesia. Catheter tip position was controlled by fluoroscopy or x-ray. The basilic vein (49) and the cephalic vein (12) were used. The total follow-up time for all systems was 323 months. Forty-five systems were still in use at the end of the observation period, six were explanted electively at the end of infusion therapy and six systems were still functioning at the time of the patient’s death (at a maximum of 14 months after implantation). Temporary arm-phlebitis was noticed on the first postoperative week in five patients. Two P.A.S. Port™ systems were explanted due to infection and one because of skin rupture at the wound. One intact system was removed as it was thought to be leaking because of needle displacement. The P.A.S. Port™ system is easy and safe to implant with a high success rate and a low complication rate. It is well accepted by patients and nurses. The device should be advantageous in patients unsuitable for standard venous portal systems and offers an excellent alternative system for venous access.

Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group

3562 Background: Oxaliplatin (Ox) in combination with FU or Capecitabine (Xel) prolong median survival as first and second line therapy in patients with advanced colorectal cancer (ACRC). Ox induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2 hour infusion is recommended, but in a prior pilot study (Pfeiffer et al, Acta Oncol 2003; 42: 832) a 30 minutes infusion could be given without additional neuropathy. Methods: For practical and economic reasons, but also for patient's convenience, we performed this phase II study to examine XELOX30 (Xel 1000 mg/m2 orally twice daily days 1–14 and Ox 130 mg/m2 as 30 minutes infusion day 1) in patients with progressive colorectal cancer after therapy with irinotecan and FU. Neuropathy was graded 0–3 using the Ox-specific scale. Other adverse events were graded using NCI-CTC. Results: From Nov 2002 to Sept 2003, 69 patients with ACRC were included and treated with XELOX30. Median age was 62 y...

During a 10 year period (1969-1978) 922 patients with facial fractures were hospitalized at the Department of Otolaryngology, Jonkoping Central County Hospital, Sweden. Eighty percent were men. The peak incidence occurred at the age of 21-30 years. The yearly number of facial fractures was doubled between 1969 and 1974, after which no marked increase was noted. The aetiologies of the fractures were fights (28%), traffic accidents (23.5%), sport activities (17.4%). There was a comparatively low number of work related facial fractures in this study (8.1%). Front seat passengers, car drivers and cyclists represented a great portion of the traffic injury group. The number of fractures caused by traffic accidents decreased after 1974, a fact that may be due to the safety-belt law. Language: en

Degradable starch microspheres (DSM) mixed and injected with a cytostatic drug might improve intra-arterial chemotherapy by increasing the local drug concentration. Several factors are of importance for an optimal effect of the microspheres, e.g. size and vascularity of the tumour, arterial blood flow and arterio-venous shunts. Therefore, the dose of DSM has to be individualized. A method for continuous monitoring of the effect of DSM was developed. A radiolabelled marker was injected intra-arterially mixed with DSM and mitomycin C. Two kinetic parameters--Passing Fraction and Marker Flow Rate--were found to be influenced by the microspheres and thus seemed to be useful for monitoring the DSM-treatment. Arterio-venous shunting was measured as passage of 99Tcm-labelled macroaggregated albumin through the liver to the lungs. Significant increase of shunting after injection of DSM was demonstrated in 15 out of 19 patients. Almost no effect of the microspheres was seen in patients with marked arterio-venous shunting or minimal reduction of the marker flow rate, but in others the passage of the labelled marker could generally be significantly reduced.

Regional chemotherapy might be more efficient if the cytostatic drug is injected together with degradable starch microspheres (DSM), which induce temporary blockage of arterioles and trap the co-injected drug in tumour. Eighteen patients with non-resectable liver cancer were included. Mitomycin C (15 mg/m2) was injected intra-arterially mixed with 900 mg of DSM every six weeks. For estimation of the effect of DSM in the liver a radiolabelled tracer was injected via the same route. Its passage through the liver to the systemic circulation was continuously measured by a detector situated over peripheral blood vessels. The effect of DSM on the tracer passage varied considerably between different patients. The study also indicated opening of new vascular pathways some minutes after the initial injection. The dose of DSM for total blockage of the arterial blood flow, indicated by angiography, also varied. In some patients 540 mg induced total occlusion. In others neither angiographic nor tracer passage were affected by the microspheres although 900 mg (or even more) were injected. Factors such as size of the vascular bed, portal and arterial blood flow and arterio-venous shunting seemed to be of great importance and should be controlled in order to optimize the use of DSM in conjunction with chemotherapy of liver tumours.

Pig liver was used to study the influence of portal blood flow and degradable starch microspheres (DSM) on the passage of radiolabelled methylene-di-phosphonate from the hepatic artery to the systemic circulation. When the portal vein was clamped abut 70 per cent of the labelled marker injected into the hepatic artery passed to the systemic circulation and the remaining 30 per cent passed when the portal vein was opened. When the flow of the hepatic artery was stopped, the portal blood flow alone drained about 65 per cent of the marker, which was given as a small volume injection into the hepatic artery. When both the arterial perfusion and the portal blood flow were closed the marker only slowly passed to the systemic circulation. DSM injected into the hepatic artery reduced the passage of the marker through the liver to 75 per cent of the reference level when the portal vein was open. When it was clamped this figure was reduced to about 25 per cent. The effect of DSM on the passage of the labelled marker was found to be dose dependent. It is suggested that the reduced passage of a labelled tracer given mixed with DSM is a useful measure of degree of arterial occlusion in the liver. However, because of the drainage via the portal system the passage cannot be completely inhibited.

The rationale for giving cytostatic drugs by the intra-arterial (i.a.) route is to achieve a regionally high concentration of drug while limiting systemic toxicity. This method can be employed for the majority of clinically detectable liver tumors, since they mainly depend on arterial blood supply, whereas small metastases are mainly supplied by the portal blood flow.1–4 The effect of i.a. administered chemotherapeutic agents has generally not been as good as expected,5–8 to some extent because of rapid washing out by the arterial flow. With the aim of reinforcing the advantages of this route of administration, manipulation of the arterial blood flow has been tried in several ways. Permanent ligation of the hepatic artery alone or combined with infusion of a cytostatic drug into an arterial catheter generally results in short-lasting tumor regression owing to the rapid development of collateral arteries to the liver.9,10

Degradable starch microspheres (DSM) injected intra-arterially together with cytostatic drugs increase the regional uptake of the drug and as a result reduce the systemic drug concentration. Previous studies have indicated that fixed doses of DSM result in different degrees of vascular occlusion and therefore variable systemic concentration of the co-injected drug. Continuous registration of the systemic concentration of 99Tcm-hydroxymethylene diphosphonate (99Tcm-HDP) co-injected intra-arterially with DSM was earlier used to monitor treatment sessions and to optimize the dose of microspheres. Further to investigate the mechanism of DSM-induced retention, the effect of DSM on the passage of this low molecular weight marker and of labelled erythrocytes (a marker confined to the blood vessels), was compared in 10 patients with liver metastases. DSM reduced the amount of 99Tcm-HDP passing through the liver by 6 to 47 per cent while the amount of erythrocytes eventually passing the liver was much less reduced (0-14%). The rate of passage, however, was significantly reduced for both labelled markers. These results indicate that substances retained by co-injection of DSM are not to a significant extent lodged within the blood vessels but diffuse into extra-vasal tissue compartments.