| 1. |
- Rasmusson, Elisabeth, et al.
(författare)
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Low rate of lymphedema after extended pelvic lymphadenectomy followed by pelvic irradiation of node-positive prostate cancer
- 2013
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Ingår i: Radiation Oncology. - 1748-717X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study was to evaluate the prevalence and severity of lower limb lymphedema after pelvic lymphadenectomy and radiotherapy to the pelvic lymph nodes in patients with prostate cancer. Methods: Twenty-six patients underwent combined treatment for high-risk node-positive prostate cancer at Skane University Hospital between April 2008 and March 2011. The treatment consisted of extended pelvic lymphadenectomy followed by androgen deprivation therapy and radiotherapy. The pelvic lymphnodes, prostate and seminal vesicles were treated with external beam radiotherapy (EBRT) to an absorbed dose of 50 Gy followed by a brachytherapy (BT) boost of 2x10 Gy to the prostate only. Twenty-two patients accepted an invitation to a clinical examination with focus on lower limb swelling. The median time between the end of radiotherapy and examination was 2.2 years (range 1.2-4.1). Results: Six patients (27%) experienced grade 1 lymphedema and two patients (9%) grade 2 while none had grade 3 or 4 according to the CTC Common Toxicity Criteria scale 4.0. Three patients required treatment with compression stockings. Conclusion: Brachytherapy and pelvic EBRT have a low incidence of lymphedema (at median 2.2 y after treatment) in patients with high-risk node-positive prostate cancer that have undergone pelvic lymph node dissection.
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| 2. |
- Bjurberg, Maria, et al.
(författare)
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Early metabolic flare in squamous cell carcinoma after chemotherapy is a marker of treatment sensitivity in vitro
- 2010
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Ingår i: Nuclear medicine and molecular imaging. - : Springer. - 1869-3474 .- 1869-3482. ; 44:3, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. Methods Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. Results The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. Conclusion A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity.
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| 3. |
- Ekblad, Lars, et al.
(författare)
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Cell-line-specific stimulation of tumor cell aggressiveness by wound healing factors - a central role for STAT3
- 2013
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 13, s. 33-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro. Methods: Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors. Results: One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3. Conclusions: In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.
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| 4. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Change in prostate volume during extreme hypo-fractionation analysed with MRI
- 2014
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Ingår i: Radiation Oncology. - 1748-717X .- 1748-717X. ; 9, s. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypo-fractionated external beam radiotherapy with narrow CTV-PTV margins is increasingly applied for prostate cancer. This demands a precise target definition and knowledge on target location and extension during treatment. It is unclear how increase in fraction size affects changes in prostate volume during treatment. Our aim was to study prostate volume changes during extreme hypo-fractionation (7 x 6.1 Gy) by using sequential MRIs. Methods: Twenty patients treated with extreme hypo-fractionation were recruited from an on-going prospective randomized phase III trial. An MRI scan was done before start of treatment, at mid treatment and at the end of radiotherapy. The prostate was delineated at each MRI and the volume and maximum extension in left-right, anterior-posterior and cranial-caudal directions were measured. Results: There was a significant increase in mean prostate volume (14%) at mid treatment as compared to baseline. The prostate volume remained enlarged (9%) at the end of radiotherapy. Prostate swelling was most pronounced in the anterior-posterior and cranial-caudal directions. Conclusions: Extreme hypo-fractionation induced a significant prostate swelling during treatment that was still present at the time of last treatment fraction. Our results indicate that prostate swelling is an important factor to take into account when applying treatment margins during short extreme hypo-fractionation, and that tight margins should be applied with caution.
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| 5. |
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| 6. |
- Lindblom, Ulrika, et al.
(författare)
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Radiation-induced trismus in the ARTSCAN head and neck trial.
- 2014
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 1651-226X .- 0284-186X. ; 53:5, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patient's oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose-response relationship for trismus. Material and methods. Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21-127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite(®) range of motion scale was used to measure maximal interincisal distance. The dose-response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. Results. No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose-response fit to the endpoint data was found for the dose to the ipsilateral masseter. Conclusions. Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensity-modulated radiation therapy will reduce problems with trismus.
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| 7. |
- Lindgren, Gustaf, et al.
(författare)
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Erythropoietin suppresses the activation of pro-apoptotic genes in head and neck squamous cell carcinoma xenografts exposed to surgical trauma.
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Several studies on the use of erythropoietin (Epo) to treat anaemia in patients undergoing cancer treatment have shown adverse effects on tumour control and survival. Experimental studies indicate that this could be linked to an interaction with wound healing processes and not an effect on tumour cells per se. We have previously shown that erythropoietin in combination with surgical trauma stimulates tumour growth. In the present study, we investigated the effect of surgery and Epo on gene expression.
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| 8. |
- Oshima, Goro, et al.
(författare)
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Autocrine epidermal growth factor receptor ligand production and cetuximab response in head and neck squamous cell carcinoma cell lines.
- 2012
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 138:3, s. 491-499
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Predictive strategies for the treatment efficacy of cetuximab are currently not available for head and neck cancer. We investigated the correlation between the expression of epidermal growth factor receptor (EGFR) ligands and EGFR expression, and the growth inhibitory activity of cetuximab in a panel of head and neck squamous cell carcinoma (HNSCC) cell lines. METHODS: The growth inhibiting effect of cetuximab was measured for eight HNSCC cell lines and correlated with the autocrine production of five EGFR ligands as measured by ELISA, and the mRNA expression of two ligands, as measured by quantitative RT-PCR. EGFR expression was assessed by western blot analysis. RESULTS: There was a good correlation between the expression of four of the EGFR ligands (TGF-α, amphiregulin, epiregulin and epigen) and the growth inhibiting effect of cetuximab. TGF-α had the highest predictive potential but had to be combined with epigen for full prediction. EGFR expression also correlated with cetuximab sensitivity but less clearly. CONCLUSIONS: The results indicate that the expression of several EGFR ligands has to be used to predict sensitivity to cetuximab in HNSCC. This has to be further evaluated in clinical samples.
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| 9. |
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| 10. |
- Ottosson, Sandra, 1981-
(författare)
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Impact of disease and treatment on body weight and eating in patients with head and neck cancer : experiences from a multicenter study
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Nutritional deterioration in patients with head and neck cancer (HNC) has a multifactorial etiology mainly associated with tumor and treatment related factors. The objective of the present thesis was to investigate the impact of the disease and treatment on body weight and eating in patients with HNC treated with radiation therapy (RT) as the single modality treatment or as preoperative RT by analyzing body weight and body mass index (BMI) over time, predictive factors for weight loss and BMI, weight loss and BMI as prognostic factors for survival, and by studying the patients’ own experience of food and eating.Methods ARTSCAN is a randomized prospective multicenter trial conducted between the years of 1998 - 2006. Data were collected during and after RT with a total follow-up time of five years. Nutritional data from the whole study cohort (n = 712), from patients with oropharyngeal cancer (n = 232) and from two of the participating treatment centers (n = 101) were retrospectively analyzed in the present thesis. In addition, interviews (n = 13) were conducted nine months after the termination of RT as part of a care development project.Results On a group level, the patients lost weight during and after RT with a nadir at five months after the termination of RT. Factors related to a higher weight loss were oropharyngeal cancer, a high BMI at the start of RT, post-treatment aspiration, no tube feeding at the start of RT, and larger treated volumes. Furthermore, a high BMI at the start of RT was shown to be significantly related to a better five-year overall survival in patients with oropharyngeal cancer, whereas weight loss was not. The patients’ own narratives showed that all aspects of food, eating and meals were affected by the remaining sequelae, and that the patients found ways to accept and cope with the changes that had to be done to facilitate eating.Conclusions and clinical implications The disease and treatment gave persistent effects on the HNC patients’ weight and BMI which calls for a prolonged nutritional follow-up. The predictive factors found for weight loss can be used during patient history to find patients at risk for nutritional deterioration. In oropharyngeal cancer, patients with a high BMI at the start of RT had the best survival. This finding indicates that patients with a low BMI should be encouraged to gain weight before RT start. All aspects of food, eating and meals were affected during and after RT, and therefore the nutritional treatment should be given with a holistic approach to meet the multifaceted need patients with HNC experience.
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