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- Ehrsson, Ylva Tiblom, et al.
(författare)
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Explorative study on the predictive value of systematic inflammatory and metabolic markers on weight loss in head and neck cancer patients undergoing radiotherapy
- 2010
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Ingår i: Supportive Care in Cancer. - : Springer Science and Business Media LLC. - 0941-4355 .- 1433-7339. ; 18:11, s. 1385-1391
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This study aimed to explore the predictive value of systematic inflammatory and metabolic markers in head and neck (H&N) cancer patients during radiotherapy (RT). Methods Twenty-seven patients were evaluated. The protocol included serial blood tests [highly sensitive C-reactive protein (hsCRP), albumin, insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1) and ghrelin], measurements of body weight and assessment of oral mucositis. Results The mean nadir of weight loss was observed at the end of RT. At the time of diagnosis, mean hsCRP was 5.2 +/- 1.0 mg/L. HsCRP significantly increased during RT and decreased during the post-RT period. Mean maximum hsCRP was 35.8 +/- 8.5 mg/L, with seven patients reaching >40 mg/L. A numerical decrease of albumin (by 18.2%) and only small changes in IGF-1, IGFBP-1 and ghrelin levels were observed. None of the metabolic parameters was significantly associated with weight loss. Conclusions HsCRP increased in response to RT for H&N cancer as a sign of irradiation-induced inflammation. Weight loss was not preceded by changes of the metabolic parameters, indicating that assessment of the blood markers used in this study is of little value. Regular body weight measurement and assessment of oral mucositis are feasible, cheap and important procedures to control the metabolic homeostasis during RT.
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| 4. |
- Tilling, Kate, et al.
(författare)
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Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer : a comparison of observational cohorts
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:3, s. 446-452
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. OBJECTIVE: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. DESIGN, SETTING, AND PARTICIPANTS: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. MEASUREMENTS: PSA level. RESULTS AND LIMITATIONS: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0 ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: -2.0 ng/ml; interquartile range [IQR]: -7.6-0.7 ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: -0.8 ng/ml; IQR: -2.1-0.1 ng/ml). CONCLUSIONS: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols.
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| 5. |
- Johansson, Bengt, 1958-
(författare)
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Long-term outcome research on PDR brachytherapy with focus on breast, base of tongue and lip cancer
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brachytherapy (BT) with continuous low dose rate (LDR) has been used for 100 years and is considered as the radiotherapy method able to deliver a dose in the shortest time with high efficacy and low risk of side effects. The drawbacks are need for patient isolation and radiation exposure of the staff during the treatment. Brenner and Hall published the radiobiology concept for pulsed dose rate (PDR) in 1991. Short (10-20 minutes), hourly pulses of high dose rate (HDR) given to the same dose, with same overall treatment time will virtually simulate continuous LDR. At the same time new afterloading machine technology became available, where a single millimetre sized radiation 192Iridium source sequentially moves through the applicator in small individually timed steps. The advantages are that the radiation dose can be optimized along the applicator and with no radiation exposure of the staff and no need for patient isolation more than during the pulse. This work deals with four different aspects of PDR BT An experimental comparison of measured absorbed doses outside a left sided breast target on a body equivalent Alderson phantom was made. Five external beam radiotherapy (EBRT) whole breast treatments to 50 Gy versus five accelerated partial breast irradiations (APBI) by PDR BT to 50 Gy were studied. The absorbed doses were measured in 67 different positions inside the body phantom by thermoluminescence dosimeters. The result shows that dose points distant to the left breast will have 1-1.4 % of the prescribed dose with no difference between EBRT and PDR BT. Organs at risk in short distance (<5 cm) to the target (such as parts of the left lung, heart muscle and the right breast) will have significantly less dose by PDR BT. In conclusion PDR BT has dosimetric advantages close to the target compared to EBRT and cannot do more damage to remote organs. PDR APBI as the adjuvant RT treatment to breast conserving surgery after early breast cancer was studied. Between 1994-2004 we treated 50 women and 51 breasts. The median age of the population was 53 (40-72) years. The cases were radically resected, unifocal T1-2N0-1M0 tumours. PDR BT was given to a dose of 50 Gy for 5 days directed to the operated sector of the breast. The median treated volume was 160 cm3, constituting in median 31 % of the breast volume. The treatment is called accelerated because total treatment time is 5 days compared to 5 weeks for EBRT. After a median follow-up of 130 months (>10 years) we noted 5 (10 %) local recurrences in the treated breast. Four of these recurrences were outside the treated volume. Three women (6 %) developed cancers in the other breast. Early side effects were mild and less than with EBRT. As late side effects we found mild to moderate local fibroses in the treated volume. A cosmetic evaluation was done by both the patient and a nurse and was found to be lower than in other published data (56 % = good to excellent). The 10 years local failure rate is similar to the result from a large Swedish randomized study on whole breast radiotherapy to 50 Gy. The study indicates that PDR BT is highly effective. A combination of EBRT (40.8 Gy) and PDR boost (35 Gy) to T1-4N0-3M0, base of tongue (BOT) cancer, treated during 1994-2007 was analyzed. The study is the first with PDR and second largest with BT worldwide. A number of 83 patients with a median age of 60 (38-82) years were included. BT was given to a mean volume of 58 ccm 2 days after the neck dissection. Median follow-up was 54 months. At 5 years we found 89 % local tumour control, 95 % neck control, 80 % disease free survival and an overall survival of 65 %. Late side effects were 13 % minor transient soft tissue necrosis and 12 % long lasting or permanent soft tissue- or osteoradio-necrosis. The results are among the best published worldwide. An extensive quality of life analysis was done on 45 patients at last follow-up and showed limited, persistent xerostomia and dysphagia. The global quality of life was rated good in 75 % of the patients. The last study presented was PDR mono-brachytherapy (55-60 Gy) to cancer of the lip (T1-3N0M0). The study included 43 patients with a median age of 74 (37-92) years. The treatment time was 5.5-6 days and the mean treated volume was 15 ccm. The median follow-up time was 54 (1-158) months. Five year Kaplan-Meier data showed, local control 94 %, disease free survival 86 % and overall survival 59 %. An early side effect was a strong radiation mucositis and dermatitis, which healed in 1 month. Late side effects were uncommon and the cosmetic appearance and the lip function were found to be normal. Our data in total and per T-stage was compared to a European survey from 1993 on 2794 patients treated by LDR BT. The results are similar and are a strong indication of equal efficacy between PDR and LDR.
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| 7. |
- Falck, Eva, et al.
(författare)
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Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma
- 2010
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Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.
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| 8. |
- Fang, Fang, et al.
(författare)
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Hospitalization for osteoarthritis and prostate cancer specific mortality among Swedish men with prostate cancer
- 2010
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Ingår i: Cancer Epidemiology. - Oxon, United Kingdom : Elsevier BV. - 1877-7821 .- 1877-783X. ; 34:5, s. 644-647
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the potential role of nonsteroidal anti-inflammatory drugs (NSAIDs) use on prostate cancer (PCa) specific mortality. Methods: We studied the association between hospitalization for osteoarthritis prior to PCa diagnosis, as a surrogate for heavy use of NSAIDs, and PCa specific mortality in a large population of PCa patients in Sweden in 1980-2004. Results: Hospitalization for osteoarthritis before PCa diagnosis was associated to a lower PCa specific mortality (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.88-0.96), but not to the risk of death from other causes (HR, 1.03; 95% Cl, 0.99-1.08). The association was stronger among younger patients and patients diagnosed in earlier calendar years. Conclusions: Our data demonstrate a modestly decreased PCa specific mortality among PCa patients with hospitalization for osteoarthritis prior to PCa diagnosis, compared to those without such experience. This finding lends support to the hypothesis that NSAIDs use may influence PCa progression.
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| 9. |
- Eilegård Wallin, Alexandra, 1975-, et al.
(författare)
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Risk of parental dissolution of partnership following the loss of a child to cancer : A population-based long-term follow-up
- 2010
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Ingår i: Archives of Pediatrics & Adolescent Medicine. - Chicago : American Medical Association. - 1072-4710 .- 1538-3628. ; 164:1, s. 100-101
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Tidskriftsartikel (refereegranskat)abstract
- A common belief is that bereaved parents are more likely to separate than others, but previous research has been unable to settle this issue owing to conflicting findings. Parents of a child with cancer are at increased risk of psychological distress and possibly also marital strain. Sirki et al studied parents who lost a child during active cancer treatment or terminal care and found that divorce was significantly more common among couples with a child in terminal care compared with a child in active cancer therapy. No conclusive studies on long-term marital status in parents having lost a child to cancer have been conducted. Therefore, we assessed parental dissolution of a partnership 4 to 9 years following the loss of a child to cancer compared with parents from the general population.
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| 10. |
- Fiorentino, Michelangelo, et al.
(författare)
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Immunohistochemical Expression of BRCA1 and Lethal Prostate Cancer
- 2010
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Ingår i: Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:8, s. 3136-3139
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 functions as a tumor suppressor; recent work suggests that BRCA1 may also induce cell cycle arrest to allow for DNA repair. We hypothesized that BRCA1 expression in prostate tumor tissue may be associated with prostate cancer progression through regulation of the cell cycle. We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from 393 prostate cancer cases in the Physicians' Health Study. The men were followed prospectively from diagnosis to development of metastases and mortality. Fifteen percent of tumors stained positive for BRCA1. BRCA1-positive tumors had substantially increased tumor proliferation index compared with negative tumors (47.0 Ki67-positive nuclei versus 10.3, P = 0.0016) and were more likely to develop lethal cancer compared with BRCA1-negative tumors (hazard ratio, 4.6; 95% confidence interval, 2.4-8.7). These findings strengthen the hypothesis that BRCA1 plays a role in cell cycle control and show that BRCA1 is a marker of clinical prostate cancer prognosis. Cancer Res; 70(8); 3136-9. (C) 2010 AACR.
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