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- Johansson, Anna L. V., et al.
(författare)
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Mortality in women with pregnancy-associated malignant melanoma
- 2014
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Ingår i: The Journal of American Academy of Dermatology. - : Elsevier BV. - 0190-9622 .- 1097-6787. ; 71:6, s. 1093-1101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malignant melanoma (MM) is one of the most common malignancies in young women. It remains debated whether a MM diagnosed during pregnancy or lactation has a worse prognosis. Objective: We sought to examine mortality in women with pregnancy-associated MM (PAMM) (diagnosed during pregnancy and up to 2-years postpartum). Methods: This was a population-based cohort study based on information retrieved from the Swedish Cancer and Multi-Generation Registers. Hazard ratios with 95% confidence intervals adjusted for age, period, education, parity, and tumor location were estimated. Results: In total, 6857 women and girls aged 15 to 44 years with a diagnosis of cutaneous MM between 1963 and 2009 were identified. Of these, 1019 cases were classified as PAMM. The cause-specific mortality did not differ between PAMM and MM not diagnosed near childbirth (adjusted hazard ratio 1.09, 95% confidence interval 0.83-1.42). Limitations: Information on stage at diagnosis was available only for a subset of patients Conclusion: Overall, the cause-specific mortality in women and girls with PAMM did not differ from that in women and girls with non-PAMM. The current findings do not provide evidence of an adverse prognostic influence of pregnancy or a recent birth.
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| 5. |
- Mosavi, Firas, et al.
(författare)
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Whole-body MRI including diffusion-weighted imaging compared to CT for staging of malignant melanoma
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:2, s. 91-97
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Tidskriftsartikel (refereegranskat)abstract
- Background. Whole-body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), has been increasingly used for the detection of metastatic disease. Purpose. To assess the value of WB MRI including DWI compared to computed tomography (CT) for staging of malignant melanoma. A second aim was to assess the value of DWI in addition to conventional MR sequences for the detection of lesions. Material and methods. WB MRI with DWI and CT chest, abdomen, and pelvis were performed in 23 patients with histologically confirmed malignant melanoma. CT before and after the MRI examinations and the clinical follow-up was utilized as the standard of reference. Results. WB MRI and WB DWI detected 345 and 302 lesions, respectively, compared to 397 lesions with CT. The sensitivity of WB MRI and WB DWI varied considerably in different regions of the body. In the lungs, WB MRI and WB DWI showed 63% and 47% true-positive lesions, respectively. WB MRI and WB DWI detected 56 bone lesions in 12 patients compared to 42 lesions in 8 patients with CT. In addition, WB MRI and WB DWI could detect 68 lesions outside the field of view of CT in six patients. Conclusion. WB MRI is still not ready to replace CT for staging of malignant melanoma, especially in the thorax region. However, WB MRI is advantageous for detection of bone lesions and lesions outside the investigated volume of the conventional CT. When WB MRI is evaluated, both DWI and conventional MRI sequences must be scrutinized.
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| 6. |
- Olofsson, Roger, 1978, et al.
(författare)
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Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
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| 7. |
- Plym, Anna, et al.
(författare)
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Clinical characteristics, management and survival in young adults diagnosed with malignant melanoma : A population-based cohort study
- 2014
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 53:5, s. 688-696
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Tidskriftsartikel (refereegranskat)abstract
- Background. Few studies to date have described the clinical features of malignant melanoma in young adulthood. Also, little is known about patterns of care in young patients. We examined and compared clinical characteristics, management and survival between young adult (15-39 years) and older adult melanoma patients in Central Sweden. Material and methods. Patients diagnosed with invasive malignant melanoma between 1997 and 2011 were identified in the Regional Quality Register of Cutaneous Malignant Melanoma in Central Sweden, a population-based register covering a source population of about two million. Data on clinical characteristics, management and survival were retrieved and compared according to age at diagnosis. Results. Of 5915 patients included in the study, 584 (9.9%) were between 15 and 39 years of age at diagnosis. Compared with older patients, young adult patients were more likely to be female, with higher proportions of thin, non-ulcerated melanomas, superficial spreading melanoma and melanomas located on the lower extremity. Young adults had shorter waiting times for surgical procedures and a higher proportion received surgical treatment according to guidelines. Overall, young patients had better relative survival than older patients. Age-related survival differences varied by stage of disease at diagnosis, and were most prominent in stage II disease. Conclusion. The observed differences in clinical characteristics, management and survival between young adult and older melanoma patients call for an improved understanding of not only disease etiology but also factors driving management decisions. A better understanding of these differences may help improve care and prognosis for melanoma patients of all ages.
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- Sadeghi, Arian, et al.
(författare)
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Rapid expansion of T cells : Effects of culture and cryopreservation and importance of short-term cell recovery
- 2013
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:5, s. 978-986
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSuccessful cell therapy relies on the identification and mass expansion of functional cells for infusion. Cryopreservation of cells is an inevitable step in most cell therapies which also entails consequences for the frozen cells.Material and methodsThis study assessed the impact of cryopreservation and the widely used protocol for rapid expansion of T lymphocytes. The effects on cell viability, immunocompetence and the impact on apoptotic and immunosuppressive marker expression were analyzed using validated assays.Results and conclusionCryopreservation of lymphocytes during the rapid expansion protocol did not affect cell viability. Lymphocytes that underwent mass expansion or culture in high dose IL-2 were unable to respond to PHA stimulation by intracellular ATP production immediately after thawing (ATP = 16 ± 11 ng/ml). However, their reactivity to PHA was regained within 48 hours of recovery (ATP = 356 ± 61 ng/ml). Analysis of mRNA levels revealed downregulation of TGF-β and IL-10 at all time points. Culture in high dose IL-2 led to upregulation of p73 and BCL-2 mRNA levels while FoxP3 expression was elevated after culture in IL-2 and artificial TCR stimuli. FoxP3 levels decreased after short-term recovery without IL-2 or stimulation. Antigen specificity, as determined by IFNγ secretion, was unaffected by cryopreservation but was completely lost after addition of high dose IL-2 and artificial TCR stimuli. In conclusion, allowing short-time recovery of mass expanded and cryopreserved cells before reinfusion could enhance the outcome of adoptive cell therapy as the cells regain immune competence and specificity.
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| 9. |
- Schadendorf, D., et al.
(författare)
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Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma : quality-of-life analyses of the METRIC study
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:3, s. 700-706
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Tidskriftsartikel (refereegranskat)abstract
- We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametinib.In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.
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| 10. |
- Staff, Caroline, et al.
(författare)
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Induction of IgM, IgA and IgE Antibodies in Colorectal Cancer Patients Vaccinated with a Recombinant CEA Protein
- 2012
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Ingår i: Journal of Clinical Immunology. - : Springer Science and Business Media LLC. - 0271-9142 .- 1573-2592. ; 32:4, s. 855-865
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Tidskriftsartikel (refereegranskat)abstract
- Previous clinical studies have indicated that natural IgM antibodies have the ability to induce apoptosis of tumor cells but IgE and IgA may also mediate tumor cell killing (in addition to IgG). The aim of the study was to analyse induction of IgM, IgA and IgE antibodies in patients vaccinated with the tumor associated antigen CEA. Twenty-four resected CRC patients without macroscopic disease were immunized seven times with CEA +/- GM-CSF. Four different dose schedules were used over a 12-month period. IgM, IgA and IgE antibody responses against recombinant CEA were determined by ELISA. Patients were monitored immunologically for 36 months and clinically for 147 months. GM-CSF significantly augmented the anti-CEA response for all three antibody classes. Low dose of CEA tended to induce a higher IgM, IgA or IgE anti-CEA antibody response than higher. Anti-CEA IgA antibodies could lyse CEA positive tumor cells in antibody dependent cellular cytotoxicity (ADCC) as well as in complement dependent cytotoxicity (CDC). A significant correlation between survival and high IgA anti-CEA titers was noted (p = 0.02) irrespective of GM-CSF treatment. The observation that IgA anti-CEA antibodies were cytotoxic and associated with improved survival might indicate that also these antibodies may exert a clinical anti-tumor effect.
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