| 1. |
- Rasmusson, Elisabeth, et al.
(författare)
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Erectile Dysfunction and Absorbed Dose to Penile Base Structures in a Randomized Trial Comparing Ultrahypofractionated and Conventionally Fractionated Radiation Therapy for Prostate Cancer
- 2020
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier. - 0360-3016 .- 1879-355X. ; 107:1, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the relationships between absorbed dose to penile base structures and erectile dysfunction (ED) in patients treated with ultrahypofractionated (UHF) radiation therapy (RT) or conventionally fractionated (CF) RT for prostate cancer.Methods and Materials: This dose-response study comprises 673 patients (57%) of the 1180 per-protocol patients included in the HYPO-RT-PC trial (median follow-up 5, years), where patients were randomized to CF (39 × 2.0 Gy, 8 weeks) or UHF (7 × 6.1 Gy, 2.5 weeks). No androgen deprivation therapy was allowed. Only patients with erectile function sufficient for intercourse at baseline and complete RT data were included in this study. Erectile function was assessed by physician at regular follow-ups. The main endpoint was severe ED (EDs). The penile bulb (PB) and crus were retrospectively delineated on the treatment planning computed tomography scans. Dose-volume descriptors were derived from EQD2 converted dose matrices (α/β = 3 Gy). Univariable and multivariable Cox proportional hazard regression and logistic regression were used to find predictors for EDS.Results: No significant difference in EDs was found between CF and UHF. During the follow-up period, EDs occurred in 27% of the patients in both treatment groups. Average (median) PB mean dose, Dmean, was 24.5 (20.2) in CF and 18.7 (13.1) Gy3 in UHF. Age was the only significant predictor for EDs in Cox analyses. All dose-volume variables contributed significantly in univariable logistic regression at 2-year follow-up. Age and near maximum dose (D2%) were significant predictors for EDs in multivariable logistic regression analyses at both 1 and 2 years.Conclusions: The frequency of EDS was similar in the CF and UHF treatment groups. Age at radiation therapy was the strongest predictor for EDs, followed by dose to PB, and was most evident for younger patients. We propose D2 % <50 Gy3 and Dmean <20 Gy3 to the PB as the primary objectives to be applied in the treatment planning process.
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| 2. |
- Rasmusson, Elisabeth, et al.
(författare)
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Long-Term Risk of Hip Complications After Radiation Therapy for Prostate Cancer : A Dose-Response Study
- 2021
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the present study was to analyze the long-term incidence of hip complications after external beam radiation therapy compared with age-matched controls from the general population. We also investigated whether there were any dose−response associations. Methods and materials: A total of 349 patients with prostate cancer treated to curative dose with external beam radiation therapy between 1997 and 2002 were included in the study. Physical and fractionation-corrected dose-volume descriptors were derived for the femoral heads, pubic bone, and sacrum. Information on skeletal events was collected for the patients and 1661 matched controls through the Prostate Cancer database Sweden. Uni- and multivariable Cox proportional hazard regressions were used to analyze the time to event. Results: Data from 346 patients were available for analysis. The median mean physical dose and corresponding equivalent 2-Gy/fraction dose (EQD2) to the femoral heads were 35.5 Gy and 28.7 Gy, respectively. The median follow-up time was 16.0 years. During the follow up, 12 hip fractures occurred. Hip osteoarthritis was diagnosed in 36 cases, with 29 cases leading to replacement surgery. No increased risk of hip fractures was found. Hip osteoarthritis was the only event for which a statistically significant difference was found between the irradiated cohort and the controls (cause-specific hazard ratio: 1.56; 95% confidence interval, 1.07-2.26; P = .02). The cumulative incidence of osteoarthritis at 10 years was 8.1% and 4.9% in the irradiated cohort and the controls, respectively. A significant relationship between osteoarthritis and the volume of the femoral head receiving ≥40 Gy (ie, EQD2) was found. Conclusions: In this study of 346 patients treated with conventional radiation therapy, we found no increased risk of hip fracture but an increased risk of clinically relevant osteoarthritis at long-term follow up. Our results indicate a dose–response relationship between osteoarthritis and the volume of the femoral head receiving an EQD2 dose of ≥40 Gy.
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| 3. |
- Rasmusson, Elisabeth, et al.
(författare)
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Low-dose rate brachytherapy with I-125 seeds has an excellent 5-year outcome with few side effects in patients with low-risk prostate cancer
- 2016
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Ingår i: Acta Oncologica. - Oxon : Taylor & Francis. - 0284-186X .- 1651-226X. ; 55:8, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-dose rate brachytherapy (LDR-BT) has been used in Sweden for more than a decade for treatment of low-risk prostate cancer. This study presents the outcome for patients treated with LDR-BT at a single institution with focus on the association between dose and biochemical failure-free survival (BFFS).Methods: In total 195 patients were treated with LDR-BT between 2004 and 2008. The patients were followed systematically for side effects for at least one year. PSA levels were followed regularly from three months and for at least five years. Outcome was analyzed in relation to clinical variables at baseline and to radiotherapy data.Results: Kaplan-Meier estimated BFFS at five years was 95.7%. Dose to the prostate in terms of D-90% was significantly associated with BFFS [HR 0.90 (95%CI 0.83-0.96), p=0.002].Conclusion: Out data confirmed that absorbed dose is a predictive factor for BFFS for low-risk patients without androgen deprivation therapy. With our treatment routines and dosimetry, a D-90% in the range of 170-180Gy gives excellent outcomes with acceptable toxicity for patients with low-risk prostate cancer.
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| 4. |
- 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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| 5. |
- Adra, Jamila, et al.
(författare)
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Distribution of locoregional breast cancer recurrence in relation to postoperative radiation fields and biological subtypes.
- 2019
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 105:2, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- and purpose: To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiotherapy (LRRT) for primary breast cancer. LRR-position in relation to applied radiotherapy and the primary tumours biological subtype were analysed with the aim to evaluate current target guidelines and RT techniques in relation to tumour biology.Medical records were reviewed for all patients who received postoperative LRRT for primary BC in southwestern Sweden from 2004-2008 (N=923). Patients with LRR as a first event were identified (N=57, distant failure and death were considered competing risks). CT images identifying LRR were used to compare LRR locations to postoperative LRRT fields. LRR risk and distribution were then related to the primary BC biological subtype and to current target guidelines.Cumulative LRR incidence after 10 years was 7.1% (95%CI 5.5-9.1). Fifty-seven of the 923 patients in the cohort developed LRR (30 local recurrences (LR), 30 regional recurrences (RR), of which 3 cases of simultaneous LR/RR). Most cases of LRR developed fully (56%) or partially (26%) within postoperatively irradiated areas. The most common location for out-of-field RR was cranial to RT fields in the supraclavicular fossa. Patients with an ER- (HR 4.6, p<0.001, 95%CI 2.5-8.4) or HER2+ (HR 2.4, p=0.007, 95%CI 1.3-4.7) primary BC presented higher risks of LRR compared to those with ER+ tumours. ER-/HER2+ tumours more frequently recurred in-field (68%) rather than marginal/out-of-field (32%). In addition, 75% of in-field recurrences derived from an ER-/HER+ tumour, compared to 45% of marginal/out-of-field recurrences. A complete pathological response in the axilla after neoadjuvant treatment was associated with a lower degree of LRR risk (p=0.022).Incidence and locations of LRR seems to be related to the primary BC biological subtype. Individualized LRRT according to tumour biology may be applied to improve outcomes.
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| 6. |
- Adrian, Gabriel, et al.
(författare)
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Altered fractionation diminishes importance of tumor volume in oropharyngeal cancer : Subgroup analysis of ARTSCAN-trial
- 2020
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Ingår i: Head and Neck. - : Wiley-Blackwell. - 1043-3074 .- 1097-0347. ; 42:8, s. 2099-2105
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Tidskriftsartikel (refereegranskat)abstract
- Background: A large tumor volume negatively impacts the outcome of radiation therapy (RT). Altered fractionation (AF) can improve local control (LC) compared with conventional fractionation (CF). The aim of the present study was to investigate if response to AF differs with tumor volume in oropharyngeal cancer.Methods: Three hundred and twenty four patients with oropharyngeal cancer treated in a randomized, phase III trial comparing CF (2 Gy/d, 5 d/wk, 7 weeks, total dose 68 Gy) to AF (1.1 Gy + 2 Gy/d, 5 d/wk, 4.5 weeks, total dose 68 Gy) were analyzed.Results: Tumor volume had less impact on LC for patients treated with AF. There was an interaction between tumor volume and fractionation schedule (P = .039). This differential response was in favor of CF for small tumors and of AF for large tumors.Conclusion: AF diminishes the importance of tumor volume for local tumor control in oropharyngeal cancer.
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| 7. |
- Adrian, Gabriel, et al.
(författare)
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Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy
- 2022
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Ingår i: Radiation Oncology. - : Springer Nature. - 1748-717X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT). Methods: Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume. Results: The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume. Conclusions: Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.
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| 8. |
- Ahlqvist-Rastad, Jane, et al.
(författare)
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Erythropoietin therapy and cancer related anaemia : updated Swedish recommendations
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:3, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks.
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| 9. |
- Andersson, S., et al.
(författare)
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Tumour Localization by Means of Laser-Induced Fluorescence in Hematoporphyrin Derivative (HPD) — Bearing Tissue
- 1985
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Ingår i: Laser Spectroscopy VII : Proceedings of the Seventh International Conference, Hawaii, June 24-28, 1985 - Proceedings of the Seventh International Conference, Hawaii, June 24-28, 1985. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 9783662152539 - 9783540396642 ; , s. 401-406
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Konferensbidrag (refereegranskat)abstract
- Following systemic injection, hematoporphyrin derivative (HPD) is known to be selectively retained in malignant tissue. This property can be used in a two-fold way: a) for localizing tumours by observing the characteristic dual-peaked laser-induced fluorescence from HPD, and b) for photodynamic therapy (HPD-PDT) using a localized HPD-assisted singlet oxygen release induced by irradiation of 630 nm laser light. This rapidly developing field has recently been reviewed by DOUGHERTY.
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| 10. |
- Berthelsen, Anne Kiil, et al.
(författare)
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What's new in target volume definition for radiologists in ICRU Report 71? How can the ICRU volume definitions be integrated in clinical practice?
- 2007
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Ingår i: Cancer Imaging. - : E-MED LTD. - 1470-7330. ; 7:1, s. 104-104
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Tidskriftsartikel (refereegranskat)abstract
- The optimal definition of the size, shape and location of gross tumour volume is one of the most important steps in the planning of radiation therapy, and necessitates a proper understanding of the procedure from both the oncologic radiologist and the radiation oncologist. This overview reports on the different terms and concepts that have been recommended in the ICRU Reports for this purpose; the latest Report 71 focuses on both previously given recommendations, and especially on electron beam therapy. This paper also highlights some of the problems that are encountered in the use of the International Commission on Radiation Units and Measurements (ICRU) recommendations in clinical practice, and at the interface between the radiation oncologist and the diagnostic oncologist.
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| 11. |
- Bjurberg, Maria, et al.
(författare)
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Early changes in 2-deoxy-2-[18F]fluoro-D-glucose metabolism in squamous-cell carcinoma during chemotherapy in vivo and in vitro.
- 2009
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Ingår i: Cancer Biotherapy & Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1557-8852 .- 1084-9785. ; 24:3, s. 327-332
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to investigate early changes in uptake of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) in vivo and in vitro in a squamous-cell carcinoma (SCC) cell line originating from a human head and neck SCC during cytotoxic therapy with respect to metabolism in tumor cells and in surrounding stromal tissue. MATERIALS AND METHODS: In 60 nude mice with xenografted SCC, 50 animals were treated with cisplatin. Early changes in the tumor FDG uptake following therapy were evaluated sequentially with phosphor imaging. Using this technique, areas with focal hypermetabolism were detected. The cells creating the focal hypermetabolism were then identified histopathologically on the corresponding sections. In addition, early FDG uptake versus the number of viable tumor cells was measured in vitro following cisplatin treatment. RESULTS: An early transient increase in FDG uptake in tumor cells was seen on day 1 in treated tumors, followed by a rapid decrease confirmed by subsequent tumor regression. This metabolic flare was present in all treated tumors but not in the controls. In vitro, an increase in FDG uptake per cell was observed. CONCLUSIONS: Our results provide new insights into the early metabolic changes in squamous-cell carcinomas subjected to cytotoxic therapy and thus contribute to the discussion on the feasibility of early predictive PET studies.
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| 12. |
- 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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| 13. |
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| 14. |
- Bjurberg, Maria, et al.
(författare)
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Prediction of patient outcome with 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography early during radiotherapy for locally advanced cervical cancer
- 2009
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Ingår i: International Journal of Gynecological Cancer. - Philadelphia : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 19:9, s. 1600-1605
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: It is difficult to assess the individual response of locally advanced cervical cancer to chemoradiation therapy during the course of treatment. We have investigated the predictive value of positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) early during treatment in relation to progression-free survival.Methods: This prospective single-center clinical trial included women with locally advanced cervical cancer from 2004 to 2008. 2-Deoxy-2-[(18)F]fluoro-D-glucose-PET/computed tomography was performed at baseline, during the third week of treatment and, finally, 3 months after the completion of treatment. The images were evaluated visually, semiquantitatively with the maximum standardized uptake value, and by calculating the metabolic rate of FDG. Thirty-two patients were eligible for full evaluation.Results: The median follow-up time was 28 months (range, 5-53 months). Visual metabolic complete response on FDG-PET, after a mean irradiation dose of 23 Gy (range, 16-27 Gy), was found in 7 patients, none of which relapsed. Eleven of the 25 patients with remaining malignant hypermetabolism on the second FDG-PET relapsed. Neither maximum standardized uptake value nor metabolic rate of FDG could further discriminate between patients with low risk and patients with high risk of relapse. The follow-up FDG-PET performed 3 months after the completion of treatment identified a group of patients with poor prognosis.Conclusions: In conclusion, FDG-PET early during chemoradiation therapy identified a small number of patients with an excellent prognosis. However, FDG-PET at this early point in time during treatment failed to predict the outcome for most patients. Future clinical trials to determine the optimal timing of predictive FDG-PET are thus warranted.
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| 15. |
- Borg, David, et al.
(författare)
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Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma : the phase II PALAESTRA trial
- 2020
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Ingår i: Acta Oncologica. - 0284-186X. ; 59:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia. Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale. Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3–4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%). Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.
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| 16. |
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| 17. |
- Brun, Eva, et al.
(författare)
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Early prediction of treatment outcome in head and neck cancer with 2-18FDG PET
- 1997
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 36:7, s. 741-747
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Tidskriftsartikel (refereegranskat)abstract
- The development of alternative treatment regimens in clinical oncology has increased the need for early prediction of cancer therapy outcome. The aim of this study was, early in the treatment phase, to identify patients with advanced head and neck cancer, responding or not responding to initiated therapy. The tumour metabolic rate of glucose (MRgl) examined by 2-18FDG-PET was determined in 17 patients before and after the first weeks of either radiotherapy (16-35 Gy) or one course of combination chemotherapy. Metabolic values uptake values normalized to plasma activity integrals--were correlated to loco-regional outcome, as evaluated 5-6 weeks after completion of treatment. Initial low tumour MRgl (<20 micromol/min/100 g tissue), in primary lesions or regional metastases, predicted a local complete response. When a high initial tumour MRgl was found, the magnitude of the reduction of MRgl in the second PET examination might be an adjunct in predicting local tumour response.
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| 18. |
- Brun, Eva, et al.
(författare)
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FDG PET studies during treatment: Prediction of therapy outcome in head and neck squamous cell carcinoma.
- 2002
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Ingår i: Head and Neck. - : Wiley. - 1043-3074. ; 24:2, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Positron emission tomography (PET) provides metabolic information of tissues in vivo. The purpose of this study was to assess the value of PET with 2-[(18) F] fluoro-2-deoxy-D-glucose (FDG) in prediction of therapy outcome (tumor response, survival, and locoregional control) in locally advanced HNSCC. METHODS: Between 1993 and 1999 47 patients underwent PET before (PET(1)) and after (PET(2)) 1 to 3 weeks of radical treatment with evaluation of metabolic rate (MR) and standardized uptake value (SUV) of FDG. All patients received radiotherapy, and 10 also received neoadjuvant chemotherapy. Median follow-up time was 3.3 years. RESULTS: Low and high MR FDG at PET(2), with median value as cutoff, was associated with complete remission in 96% and 62% (p =.007), with 5-year overall survival in 72% and 35% (p =.0042) and with local control in 96% and 55% (p =.002), respectively. CONCLUSIONS: FDG PET in the early phase of treatment of HNSCC is associated with tumor response, survival, and local control. Copyright 2002 John Wiley & Sons, Inc.
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| 19. |
- Brun, Eva, et al.
(författare)
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Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas
- 2001
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 40:4, s. 491-496
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.
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| 20. |
- Degerfält, Jan, et al.
(författare)
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E-learning programs in oncology : a nationwide experience from 2005 to 2014
- 2017
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Ingår i: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: E-learning is an established concept in oncological education and training. However, there seems to be a scarcity of long-term assessments of E-learning programs in oncology vis-á-vis their structural management and didactic value. This study presents descriptive, nationwide data from 2005 to 2014. E-learning oncology programs in chemotherapy, general oncology, pain management, palliative care, psycho-social-oncology, and radiotherapy, were reviewed from our databases. Questionnaires of self-perceived didactic value of the programs were examined 2008-2014.Results: The total number of trainees were 4693, allocated to 3889 individuals. The trainees included medical doctors (MDs; n = 759), registered nurses (RNs; n = 2359), radiation therapy technologists (n = 642), and, social and health care assistants (SHCAs; n = 933). The E-learning covered 29 different program classifications, comprising 731 recorded presentations, and covering 438 themes. A total of 490 programs were completed by the trainees. The European Credit Transfer and Accumulation System (ECTS; 1 ECTS point equals 0.60 US College Credit Hours) points varied across the educational programs from 0.7 to 30.0, corresponding to a duration of full-time studies ranging between 15 to 900 h (0.4-24 weeks) per program. The total number of ECTS points for the trainee cohort, was 20,000 corresponding to 530,000 full-time academic hours or 324.0 standard academic working years. The overall drop-out rate, across professions and programs, was 10.6% (499/4693). The lowest drop-out rate was seen for RNs (4.3%; P < 0.0001). Self-reported evaluation questionnaires (2008-2014) were completed by 72.1% (2642/3666) of the trainees. The programs were overall rated, on a 5-categorical scale (5 = excellent; 1 = very inferior), as excellent by 68.6% (MDs: 64.9%; RNs: 66.8%; SHCAs: 77.7%) and as good by 30.6% (MDs: 34.5%; RNs: 32.4%; SHCAs: 21.5%) of the responders.Conclusions: This descriptive study, performed in a lengthy timeframe, presents high-volume data from multi-professional, oncological E-learning programs. While the E-learning paradigm, across professions, seems to have been well received, it is imperative that prospective studies, benchmarking against traditional training methods, are carried out, examining the hypothesized didactic value of our E-programs.
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| 21. |
- Edvardsson, Anneli, et al.
(författare)
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Comparative treatment planning study for mediastinal Hodgkin’s lymphoma : impact on normal tissue dose using deep inspiration breath hold proton and photon therapy
- 2019
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Ingår i: Acta Oncologica. - 0284-186X. ; 58:1, s. 95-104
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late effects induced by radiotherapy (RT) are of great concern for mediastinal Hodgkin’s lymphoma (HL) patients and it is therefore important to reduce normal tissue dose. The aim of this study was to investigate the impact on the normal tissue dose and target coverage, using various combinations of intensity modulated proton therapy (IMPT), volumetric modulated arc therapy (VMAT) and 3-dimensional conformal RT (3D-CRT), planned in both deep inspiration breath hold (DIBH) and free breathing (FB). Material and methods: Eighteen patients were enrolled in this study and planned with involved site RT. Two computed tomography images were acquired for each patient, one during DIBH and one during FB. Six treatment plans were created for each patient; 3D-CRT in FB, 3D-CRT in DIBH, VMAT in FB, VMAT in DIBH, IMPT in FB and IMPT in DIBH. Dosimetric impact on the heart, left anterior descending (LAD) coronary artery, lungs, female breasts, target coverage, and also conformity index and integral dose (ID), was compared between the different treatment techniques. Results: The use of DIBH significantly reduced the lung dose for all three treatment techniques, however, no significant difference in the dose to the female breasts was observed. Regarding the heart and LAD doses, large individual variations were observed. For VMAT, the mean heart and LAD doses were significantly reduced using DIBH, but no significant difference was observed for 3D-CRT and IMPT. Both IMPT and VMAT resulted in improved target coverage and more conform dose distributions compared to 3D-CRT. IMPT generally showed the lowest organs at risk (OAR) doses and significantly reduced the ID compared to both 3D-CRT and VMAT. Conclusions: The majority of patients benefited from treatment in DIBH, however, the impact on the normal tissue dose was highly individual and therefore comparative treatment planning is encouraged. The lowest OAR doses were generally observed for IMPT in combination with DIBH.
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| 22. |
- Ekblad, Lars, et al.
(författare)
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Anti- or pro-proliferation - Conditional options for TGF-α and cetuximab in head and neck squamous cell carcinoma.
- 2015
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Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 51:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- Cetuximab is an epidermal growth factor receptor (EGFR)-targeting drug that has shown effects in head and neck squamous cell carcinoma (HNSCC). The effects are, however, small and have mainly been proven in a subset of patients, and the cost-effectiveness has been questioned. For this reason, we need to know more about the basic mechanisms controlling the effect of EGFR signalling on tumour growth.
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| 23. |
- 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. ; 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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| 24. |
- Forsell-Aronsson, E, et al.
(författare)
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Medical imaging for improved tumour characterization, delineation and treatment verification
- 2002
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:7-8, s. 604-614
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and potentials were described by an expert group for each of nine major areas of radiation therapy research, This report deals with medical imaging for improved medical diagnosis including tumour detection, staging and characterization, treatment planning, guiding and verification, evaluation of response and treatment follow-up.
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| 25. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 26. |
- Gebre-Medhin, Maria, et al.
(författare)
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Dose-volume analysis of radiation-induced trismus in head and neck cancer patients
- 2016
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Ingår i: Acta Oncologica. - 0284-186X. ; 55:11, s. 1313-1317
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Trismus is a treatment-related late side effect in patients treated for cancer in the head and neck region (HNC). The condition can have a considerable negative impact on nutrition, dental hygiene, ability to speak and quality of life. We have previously studied trismus within the frame of a randomized phase 3 study of HNC patients treated with mainly three-dimensional (3D) conformal radiotherapy (CRT) and found a strong association to mean radiation dose to the mastication muscles, especially the ipsilateral masseter muscle (iMAS). In the present study we have investigated trismus prevalence and risk factors in a more recent cohort of patients, treated with todays’ more updated radiation techniques. Material and methods: Maximal interincisal distance (MID) was measured on 139 consecutive patients. Trismus was defined as MID ≤35 mm. Patient-, disease- and treatment-specific data were retrospectively recorded. Differences between groups were analyzed and mean absorbed dose to mastication structures was evaluated. Dosimetric comparisons were made between this study and our previous results. Results: The prevalence of trismus was 24% at a median of 16 months after completion of radiotherapy. In bivariate analysis treatment technique (3DCRT vs. intensity modulated radiotherapy or helical tomotherapy), tumor site (oropharynx vs. other sites) and mean radiation doses to the ipsilateral lateral pterygoid muscle, the paired masseter muscles and the iMAS were significantly associated with MID ≤35 mm. In multivariable analysis only mean radiation dose to the iMAS was significantly associated to MID ≤35 mm. Conclusion: Mean radiation dose to the ipsilateral masseter muscle is an important risk factor for trismus development. Dose reduction to this structure during radiotherapy should have a potential to diminish the prevalence of trismus in this patient group.
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| 27. |
- Glimelius, Bengt, et al.
(författare)
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Interactions between chemotherapy, endocrine therapy and radiation
- 2002
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 41:7-8, s. 635-638
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Tidskriftsartikel (refereegranskat)abstract
- In an investigation by the Swedish Cancer Society, an expert group described the present status, critical issues and future aspects and potentials for each of nine major areas of radiation therapy research. This report deals with interactions between chemotherapy, endocrine therapy, other anti-tumour drugs and radiation.
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| 28. |
- Gretarsson, Sigurdur, et al.
(författare)
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Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines
- 2020
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 140:4, s. 337-343
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Tidskriftsartikel (refereegranskat)abstract
- Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.
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| 29. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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A prospective phase II study of prostate-specific antigen-guided salvage radiotherapy and Ga-68-PSMA-PET for biochemical relapse after radical prostatectomy-The PROPER 1 trial
- 2022
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 36, s. 77-82
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The treatment of biochemical recurrence (BCR) after prostatectomy is challenging as the site of the recurrence is often undetectable. Our aim was to test a personalised treatment concept for BCR based on PSA kinetics during salvage radiotherapy (SRT) combined with prostate-specific membrane antigen positron emission tomography (PSMA-PET). Materials and methods: This phase II trial included 100 patients with BCR. PSMA-PET was performed at baseline. PSA was measured weekly during SRT. Initially, 70 Gy in 35 fractions was prescribed to the prostate bed. Radiotherapy was adapted after 50 Gy. Non-responders (PSA still >= 0.15 ng/mL) received sequential lymph node irradiation with a boost to PSMA-PET positive lesions, while responders (PSA < 0.15 ng/mL) continued SRT as planned. PET-findings were only taken into consideration for treatment planning in case of PSA non-response after 50 Gy. Results: Data from 97 patients were eligible for analysis. Thirty-four patients were classified as responders and 63 as non-responders. PSMA-PET was positive in 3 patients (9%) in the responder group and in 22 (35%) in the non-responder group (p = 0.007). The three-year failure-free survival was 94% for responders and 68% for non-responders (median follow-up 38 months). There were no significant differences in physician-reported urinary and bowel toxicity. Patient-reported diarrhoea at end of SRT was more common among non-responders. Conclusion: This new personalised treatment concept with intensified SRT based on PSA response demonstrated a high tumour control rate in both responders and non-responders. These results suggest a clinically significant effect with moderate side effects in a patient group with otherwise poor prognosis. PSMA-PET added limited value. The treatment approach is now being evaluated in a phase III trial.
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| 30. |
- 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. ; 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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| 31. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Dose-volume relationships between enteritis and irradiated bowel volumes during 5-fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 46:7, s. 937-944
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Radiation enteritis is the main acute side-effect during pelvic irradiation. The aim of this study was to quantify the dose-volume relationship between irradiated bowel volumes and acute enteritis during combined chemoradiotherapy for rectal cancer. Material and methods. Twenty-eight patients with locally advanced rectal cancer received chemoradiotherapy. The radiation therapy was given with a traditional multi-field technique to a total dose of 50 Gy, with concurrent 5-Fluorouracil (5-FU) and oxaliplatin (OXA) based chemotherapy. All patients underwent three-dimensional CT-based treatment planning. Individual loops of small and large bowel as well as a volume defined as "whole abdomen'' were systematically contoured on each CT slice, and dose-volume histograms were generated. Diarrhea during treatment was scored retrospectively according to the NCI Common Toxicity Criteria scale. Results. There was a strong correlation between the occurrence of grade 2 + diarrhea and irradiated small bowel volume, most notably at doses > 15 Gy. Neither irradiated large bowel volume, nor irradiated "whole abdomen'' volume correlated significantly with diarrhea. Clinical or treatment related factors such as age, gender, hypertension, previous surgery, enterostomy, or dose fractionation (1.8 vs. 2.0 Gy/fraction) did not correlate with grade 2 + diarrhea. Discussion. This study indicates a strong dose-volume relationship between small bowel volume and radiation enteritis during 5-FU-OXA-based chemoradiotherapy. These findings support the application of maneuvers to minimize small bowel irradiation, such as using a "belly board'' or the use of IMRT technique aiming at keeping the small bowel volume receiving more than 15 Gy under 150 cc.
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| 32. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Multicentre phase II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable colorectal cancer : The CORGI-L study
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:5, s. 807-813
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This study assessed radiotherapy combined with capecitabine and oxaliplatin in patients with primary, inextirpable colorectal adenocarcinoma. PATIENTS AND METHODS: Forty-nine patients entered the trial. Two cycles of XELOX (capecitabine 1000mg/m(2) bid d1-14+oxaliplatin 130mg/m(2) d1, q3w) were followed by radiotherapy (50.4Gy), combined with capecitabine 825mg/m(2) bid every radiotherapy day and oxaliplatin 60mg/m(2) once weekly. The primary end-point was objective response. RESULTS: Forty-seven patients were evaluable. Twenty-nine (62% [95% CI: 46-75%]) achieved complete or partial response. Thirty-eight (81%) went through surgery of whom 37 (97%) had an R0 resection and five (13%) had a pathological complete response. Seventy-eight percent were alive and estimated local progression rate was 11% at 2 years. The most common grade 3+ toxicity during chemoradiotherapy was diarrhoea (24%). CONCLUSIONS: XELOX-RT was feasible and showed promising efficacy when treating patients with primary inextirpable colorectal cancer, establishing high local control rate.
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| 33. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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PSA decay during salvage radiotherapy for prostate cancer as a predictor of disease outcome – 5 year follow-up of a prospective observational study
- 2020
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Ingår i: Clinical and Translational Radiation Oncology. - : Elsevier BV. - 2405-6308. ; 24, s. 23-28
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Biochemical recurrence after prostatectomy is commonly treated with salvage radiotherapy (SRT). In this prospective observational study we investigated the PSA decay rate, determined by predefined serial PSA measurements during SRT, as a predictor for treatment outcome.Materials and methods: Between 2013 and 2016, 214 patients were included in the study. The prescribed dose to the prostate bed was 70 Gy in 35 fractions (7 weeks) without hormonal treatment. PSA was measured weekly during SRT. Assuming first order kinetics, a PSA decay-rate constant (k) was calculated for 196 eligible patients. The ability of k to predict disease progression was compared with known clinical prediction parameters using Cox regression, logistic regression and ROC analyses. Disease progression was defined as continuously rising PSA after SRT, PSA increase by ≥0.2 ng/ml above nadir after SRT, hormonal treatment or clinical progression.Results: After a median follow up of 4.7 years the estimated failure-free survival at 5 years was 56%. The PSA decay-rate constant (k) was found to be the strongest predictor of disease progression in both uni-and multivariable analyses.Conclusion: The addition of k to established clinical variables significantly improves the possibility to predict treatment outcome after SRT and could be used to personalize future therapies.
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| 34. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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Target definition in radiotherapy of prostate cancer using magnetic resonance imaging only workflow
- 2019
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 9, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- In magnetic resonance (MR) only radiotherapy, the target delineation needs to be performed without computed tomography (CT). We investigated in thirteenpatients with prostate cancer, how the clinical target volume (CTV) was affected, when the target delineation procedure was changed from using both CT and MRimages to using MR images only. The mean volume of the CTVCT/MR was 61.0 cm3 as compared to 49.9 cm3 from MR-only based target delineation, corresponding toan average decrease of 18%. Our results show that CTVMR-only was consistently smaller than CTVCT/MR, which has to be taken into consideration before clinicalcommissioning of MR-only radiotherapy.
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| 35. |
- Gunnlaugsson, Adalsteinn, et al.
(författare)
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The effect on the small bowel of 5-FU and oxaliplatin in combination with radiation using a microcolony survival assay
- 2009
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Ingår i: Radiation Oncology. - London : BioMed Central. - 1748-717X. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In locally advanced rectal cancer, 5-Fluorouracil (5-FU)-based chemoradiation is the standard treatment. The main acute toxicity of this treatment is enteritis. Due to its potential radiosensitizing properties, oxaliplatin has recently been incorporated in many clinical chemoradiation protocols. The aim of this study was to investigate to what extent 5-FU and oxaliplatin influence the radiation (RT) induced small bowel mucosal damage when given in conjunction with single or split dose RT.Methods: Immune competent balb-c mice were treated with varying doses of 5-FU, oxaliplatin (given intraperitoneally) and total body RT, alone or in different combinations in a series of experiments. The small bowel damage was studied by a microcolony survival assay. The treatment effect was evaluated using the inverse of the slope (D(0)) of the exponential part of the dose-response curve.Results: In two separate experiments the dose-response relations were determined for single doses of RT alone, yielding D(0) values of 2.79 Gy (95% CI: 2.65 - 2.95) and 2.98 Gy (2.66 - 3.39), for doses in the intervals of 5-17 Gy and 5-10 Gy, respectively. Equitoxic low doses (IC5) of the two drugs in combination with RT caused a decrease in jejunal crypt count with significantly lower D(0): 2.30 Gy (2.10 - 2.56) for RT+5-FU and 2.27 Gy (2.08 - 2.49) for RT+oxaliplatin. Adding both drugs to RT did not further decrease D(0):2.28 Gy (1.97 - 2.71) for RT+5-FU+oxaliplatin. A clearly higher crypt survival was noted for split course radiation (3 x 2.5 Gy) compared to a single fraction of 7.5 Gy. The same difference was seen when 5-FU and/or oxaliplatin were added.Conclusion: Combining 5-FU or oxaliplatin with RT lead to an increase in mucosal damage as compared to RT alone in our experimental setting. No additional reduction of jejunal crypt counts was noted when both drugs were combined with single dose RT. The higher crypt survival with split dose radiation indicates a substantial recovery between radiation fractions. This mucosalsparing effect achieved by fractionation was maintained also when chemotherapy was added.
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| 36. |
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| 37. |
- Henriksson, Eva, et al.
(författare)
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2-deoxy-2-[F-18]fluoro-D-glucose uptake and correlation to intratumoral heterogeneity
- 2007
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Ingår i: Anticancer research. - 1791-7530. ; 27:4B, s. 2155-2159
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in relation to the intratumoral histopathological appearance. Materials and Methods: Intratumoral distribution of FDG in nude mice with xenografted tumours originating from an established head and neck squamous cell carcinoma was studied. FDG uptake and the con-elation to histopathological appearance was evaluated in four separate quarters of each tumour. Results: Variations in FDG uptake correlating to the presence of tumour cells was demonstrated. Quarters containing more than 50% tumour cells showed a significantly higher FDG uptake (p=0.028) than quarters with more stromal tissue and necrosis. Conclusion: This Study shows that the heterogenic FDG uptake within a tumour correlates to histopathological findings and that the variable appearance of tracer uptake on the PET scan depends on distribution of different tissue components in the tumour. This intratumoral heterogeneity calls for caution when evaluating a PET scan where median values of larger areas will be misguiding and thus small areas with high uptake should be regarded as the regions of interest.
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| 38. |
- Henriksson, Eva, et al.
(författare)
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Comparison of cisplatin sensitivity and the 18F fluoro-2-deoxy 2 glucose uptake with proliferation parameters and gene expression in squamous cell carcinoma cell lines of the head and neck
- 2009
-
Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 28
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Tidskriftsartikel (refereegranskat)abstract
- Background: The survival of patients with locally advanced head and neck cancer is still poor, with 5-year survival rates of 24-35%. The identification of prognostic and predictive markers at the molecular and cellular level could make it possible to find new therapeutic targets and provide "taylor made" treatments. Established cell lines of human squamous cell carcinoma (HNSCC) are valuable models for identifying such markers. The aim of this study was to establish and characterize a series of cell lines and to compare the cisplatin sensitivity and 18F fluoro-2 deoxy 2 glucose (18F-FDG) uptake of these cell lines with other cellular characteristics, such as proliferation parameters and TP53 and CCND1 status. Methods: Explant cultures of fresh tumour tissue were cultivated, and six new permanent cell lines were established from 18 HNSCC cases. Successfully grown cell lines were analysed regarding clinical parameters, histological grade, karyotype, DNA ploidy, and index and S-phase fraction (Spf). The cell lines were further characterized with regard to their uptake of 18F-FDG, their sensitivity to cisplatin, as measured by a viability test ( crystal violet), and their TP53 and CCND1 status, by fluorescence in situ hybridization (FISH), polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) with DNA sequencing and, for cyclin D1, by immunohistochemistry. Results: Patients with tumours that could be cultured in vitro had shorter disease-free periods and overall survival time than those whose tumours did not grow in vitro, when analysed with the Kaplan-Meier method and the log-rank test. Their tumours also showed more complex karyotypes than tumours from which cell lines could not be established. No correlation was found between TP53 or CCND1 status and 18F-FDG uptake or cisplatin sensitivity. However, there was an inverse correlation between tumour cell doubling time and 18F-FDG uptake. Conclusion: In vitro growth of HNSCC cells seem to be an independent prognostic factor, with cell lines being more readily established from aggressive tumours, a phenomenon more dependent on the molecular genetic characteristics of the tumour cells than on tumour location or TNM status.
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| 39. |
- Henriksson, Eva, et al.
(författare)
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Differences in estimates of cisplatin-induced cell kill in vitro between colorimetric and cell count/colony assays
- 2006
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Ingår i: In Vitro Cellular & Developmental Biology - Animal. - 1071-2690. ; 42:10, s. 320-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate some bioassays that are different in principle: cell counting, colony forming assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB), crystal violet, and alamarBlue, with respect to their ability to measure cisplatin-induced cell death of in vitro-cultivated squamous cell carcinoma of the head and neck (SCCHN). Cisplatin was applied in concentrations of 1.0, 5.0, 10.0, 50.0, and 100 mu M. The cells were incubated for 1 h, and the cell survival was measured 5 d after treatment. We found the colorimetric assays and cell counting to be comparable. The colony forming assay indicated a higher degree of cell kill compared with the other techniques. Measurement of cell survival after treatment with cisplatin can be done by use of any of the above tested assays. However, the majority of SCCHN cell lines available do not form colonies easily, or at all. Therefore, comparing the chemosensitivity between such cell lines is limited to alternative assays. In this respect, any of the tested colorimetric assays can be used. However, they seem to underestimate cell kill. Cell counting is also an alternative. This technique, however, is time consuming and operator dependent, as in the ease of manual counting, or relatively expensive when counting is performed electronically, compared with the colorimetric assays.
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| 40. |
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| 41. |
- Jóhannesson, Vilberg, et al.
(författare)
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Adaptive sequential plan-on-plan optimization during prostate-specific antigen response guided radiotherapy of recurrent prostate cancer
- 2021
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Ingår i: Physics and imaging in radiation oncology. - : Elsevier BV. - 2405-6316. ; 18, s. 5-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment adaptation based on tumour biomarker response during radiotherapy of prostate cancer, could be used for both escalation and de-escalation of radiation doses and volumes. To execute an adaptation involving extension of treatment volumes during radiation can however be restricted by the doses already delivered. The aim of this work was to develop a treatment planning method that addresses this challenge. Material and methods: A volumetric-modulated-arc-therapy (VMAT) planning method with sequential plan-on-plan optimization was developed for a prospective phase II trial including 100 patients on salvage radiotherapy (SRT) for prostate cancer recurrence. A treatment adaptation was performed after five weeks of SRT based on prostate-specific antigen response during this phase of the treatment. This involved extension of treatment volumes for non-responders (n = 64) to include pelvic lymph nodes and boost to 68Gallium-Prostate-Specific-Membrane-Antigen-Positron-Emission-Tomography positive lesions. This method was evolved by introducing an EQD2 (equivalent dose in 2.0 Gy fractions) correction of the base plan for improved dose coverage. Results: All dose-volume criteria for target coverage were met for the non-responders when based on physical dose. An EQD2 correction of the base plan for non-responders, implemented for the final 29 patients, led to a statistically significant improvement in dose coverage as compared to the 35 patients treated without EQD2 correction. Conclusions: This is to our knowledge the only study presented on biomarker-guided sequential VMAT radiotherapy using a plan-on-plan technique in the pelvis. By using a biologically adapted technique an improved target coverage was achieved without compromising doses to organs at risk.
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| 42. |
- Jóhannesson, Vilberg, et al.
(författare)
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Dose-volume relationships of planned versus estimated delivered radiation doses to pelvic organs at risk and side effects in patients treated with salvage radiotherapy for recurrent prostate cancer
- 2024
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Ingår i: Technical Innovations and Patient Support in Radiation Oncology. - 2405-6324. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate estimated delivered dose distributions using weekly cone-beam computed tomography (CBCT) scans for pelvic organs at risk (OARs) in salvage radiotherapy (SRT) after radical prostatectomy. Furthermore, to compare them with the originally planned dose distributions and analyse associations with gastrointestinal (GI) and genitourinary (GU) side effects.METHODS: This study is part of a phase II trial involving SRT for recurrent prostate cancer. Treatment was personalised based on PSA response during SRT, classifying patients as PSA responders or non-responders. Estimated radiation dose distributions were obtained using deformable image registration from weekly CBCT scans. GI and GU toxicities were assessed using the RTOG toxicity scale, while patient-reported symptoms were monitored through self-assessment questionnaires.RESULTS: The study included 100 patients, with similar treatment-related side effects observed in both responders and non-responders. Differences in dose-volume metrics between the planned and estimated delivered doses for the examined OARs were mostly modest, although generally statistically significant. We identified statistically significant associations between QUANTEC-recommended dose-volume constraints and acute bowel toxicity, as well as late urinary patient-reported symptoms, for both the estimated delivered and planned dose distributions.CONCLUSION: We found small but statistically significant differences between estimated delivered and planned doses to OARs. These differences showed trends toward improved associations for estimated delivered dose distributions with side effects. Enhanced registration methods and imaging techniques could potentially further enhance the assessment of truly delivered doses and yield more reliable dose-volume constraints for future therapies.
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| 43. |
- Johannsson, Oskar T, et al.
(författare)
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Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier
- 2003
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Ingår i: Laboratory Investigation. - 1530-0307. ; 83:3, s. 96-387
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Tidskriftsartikel (refereegranskat)abstract
- A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.
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| 44. |
- Johansson, Karl-Axel, et al.
(författare)
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The quality assurance process for the ARTSCAN head and neck study - a practical interactive approach for QA in 3DCRT and IMRT.
- 2008
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 87:2, s. 290-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
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| 45. |
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| 46. |
- Killander, Fredrika, et al.
(författare)
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No Increased Cardiac Mortality or Morbidity of Radiation Therapy in Breast Cancer Patients After Breast-Conserving Surgery : 20-Year Follow-up of the Randomized SweBCGRT Trial
- 2020
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 107:4, s. 701-709
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Tidskriftsartikel (refereegranskat)abstract
- PurposeRadiation therapy (RT) after breast-conserving surgery reduces locoregional recurrences and improves survival but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomized clinical trial initiated in 1991 and to report dose-volume data based on individual 3-dimensional treatment plans for organs at risk.Methods and MaterialsThe trial included 1187 patients with T1-2 N0 breast cancer randomized to postoperative tangential whole breast RT or no further treatment. The prescription dose to the clinical target volume was 48 to 54 Gy. We present 20-year follow-up on survival, cause of death, morbidity, and later malignancies. For a cohort of patients (n = 157) with accessible computed tomography–based 3-dimensional treatment plans in Dicom-RT format, dose-volume descriptors for organs at risk were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques.ResultsThe cumulative incidence of cardiac mortality was 12.4% in the control group and 13.0% in the RT group (P = .8). There was an increase in stroke mortality: 3.4% in the control group versus 6.7% in the RT group (P = .018). Incidences of contralateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1), and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0).ConclusionsIn this trial, serious late side effects of whole breast RT were limited and less than previously reported in large meta-analyses. We observed no increase in cardiac mortality in irradiated patients. Doses to the heart were a median Dmean of 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.
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| 47. |
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| 48. |
- Kjellén, Elisabeth, et al.
(författare)
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A Phase I/II Evaluation of Metoclopramide as a Radiosensitiser in Patients with Inoperable Squamous Cell Carcinoma of the Lung
- 1995
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 31:13-14, s. 2196-2202
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
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| 49. |
- Kjellén, Elisabeth, et al.
(författare)
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Comparison of low dose nicotinamide versus benzamide, administered per os, as radiosensitizers in a C3H mammary carcinoma
- 1988
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 1879-0887 .- 0167-8140. ; 12:4, s. 327-331
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Tidskriftsartikel (refereegranskat)abstract
- We have evaluated if any differences in tumor radiosensitization exist between the two adenosine diphosphate ribosyl transferase (ADPRT) inhibitors nicotinamide and benzamide at fractionated low doses. A significant radiosensitizing effect with nicotinamide at a 10 mg/kg per day dose was found in the tumor model used. We found, however, no radiosensitizing effect with benzamide given according to this schedule.
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| 50. |
- Kjellén, Elisabeth, et al.
(författare)
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Effect of hyperthermia and/or nicotinamide on the radiation response of a C3H mammary carcinoma
- 1989
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Ingår i: European journal of cancer & clinical oncology. - : Elsevier BV. - 0277-5379. ; 25:12, s. 1733-1737
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Tidskriftsartikel (refereegranskat)abstract
- The effect of hyperthermia and/or nicotinamide (200 mg/kg of body weight) on the tumour growth delay induced by radiation was evaluated in a C3H mouse mammary adenocarcinoma. The study showed a radiosensitizing effect of hyperthermia and of nicotinamide but the combination of all three modalitites showed no increased tumor growth delay compared to hyperthermia and radiation alone. The tumour growth delay induced by hyperthermia was not modified by nicotinamide.
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