| 1. |
- Karlsson, Johannes, et al.
(författare)
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Differences in outcome for cervical cancer patients treated with or without brachytherapy
- 2017
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Ingår i: Brachytherapy. - Philadelphia, USA : Elsevier. - 1538-4721 .- 1873-1449. ; 16:1, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare the clinical outcome of cervical cancer patients treated with primary radiotherapy with and without the addition of brachytherapy.Methods and Materials: In all, 220 patients with cervical cancer stage I-IV treated between 1993 and 2009 were included. Three or five 6.0 Gy fractions of brachytherapy were given in addition to the external beam radiotherapy to 134 patients, whereas 86 patients received external beam radiotherapy alone (EBRTA). In the EBRTA group, the patients received external boost instead of brachytherapy with a total dose to the tumor of 64-72 Gy.Results: The 5-year overall survival and cancer-specific survival rates of the complete series were 42.5% and 55.5%, respectively. The rates of primary complete remission, 5-year cancer-specific survival, and recurrence were 92.5%, 68.5%, and 31.3% for the brachytherapy group vs. 73.3%, 35.4%, and 37.2% for the EBRTA group. The survival (all types) of the patients receiving brachytherapy was significantly (p < 0.0001) better than for the patients treated with external boost, but the difference was most pronounced in FIGO stage II tumors. Higher FIGO stage, nonsquamous cell carcinoma histology, treatment with EBRTA, and lower total equal 2-Gy (EQD2) external dose were significantly associated with poorer survival, lower rate of remission, and higher recurrence rate in multivariate models.Conclusions: Primary tumor remission rate, recurrence rate, and all types of survival rates were improved in the brachytherapy group. Brachytherapy is important to achieve sufficient doses to the periphery and central part of the tumor and should always be considered in treatment of cervical carcinomas.
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| 2. |
- Bohr Mordhorst, Louise, 1958-, et al.
(författare)
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A study of serum biomarkers associated with relapse of cervical cancer
- 2012
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:11, s. 4913-22
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients with cervical cancer that differentiate between patients with relapse from those who are tumor-free after primary treatment with (platinum-based chemo-) radiation.PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from patients with advanced cervical cancer, primarily treated with (platinum-based chemo-) radiation.RESULTS: Ten candidate biomarkers were identified in the serum of 34 patients. Six candidate markers were elevated in patients with no relapse and four were elevated in patients with relapse [p=0.007-0.11; area under the curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to 116,165 Da.CONCLUSION: Patients with relapse from primary advanced cervical cancer exhibit different serum protein expression profiles from those with no relapse.
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| 3. |
- Bohr Mordhorst, Louise, 1958-
(författare)
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Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A series of 131 women with cervical carcinoma FIGO stage I-IV were treated with external radiotherapy and intracavitary brachytherapy. In 47 patients (36%) concomitant chemotherapy was given. One hundred and twenty-one tumors (92%) achieved complete remission. Addition of chemotherapy increased primary cure rate to 98%. Tumor stage, tumor size, and histology were significant predictive factors for primary cure. Treatment related factors were: brachytherapy dose and interruption of irradiation.Thirty-nine recurrences (30%) were recorded. Tumor stage, histology, and concomitant chemotherapy were significant predictive factors.The 5-year cancer-specific survival rate of the complete series was 65%. Tumor size was a strong prognostic factor in multivariate analysis.Serum samples from 44 patients were analyzed. Ten candidate biomarker proteins with regard to tumor recurrences were identified.Five Hedgehog proteins were analyzed with immunohistochemistry. Residual tumor, local and distant recurrences and survival rate were associated with PTCH, SMO and GLI2. In the Wnt-β-catenin study intense staining of the membranes and nuclear staining > 5% were of significant predictive and prognostic value. Intense nuclear APC staining was associated with recurrences and cancer-specific survival rate.Conclusion: Histology, tumor size and brachytherapy dose were important clinical predictive and prognostic factors. Multiprotein analysis identified ten biomarker proteins associated with tumor recurrences. Three proteins (PTCH, SMO, and GLI2) in the Hedgehog pathway were of predictive and prognostic value. In the Wnt-β-catenin pathway intensity of β-catenin membrane staining and accumulation in the nuclei as well as nuclear APC-expression were of predictive and prognostic value.
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| 4. |
- Bohr Mordhorst, Louise, 1958-, et al.
(författare)
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Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy
- 2014
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Ingår i: Gynecologic Oncology. - : Academic Press. - 0090-8258 .- 1095-6859. ; 135:2, s. 305-311
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hedgehog signaling proteins were assessed in patients with cervical carcinoma receiving chemoradiation. Associations between five Hedgehog proteins and prognosis were studied.Methods: In all, 131 cases of cervical carcinomas (FIGO stages I-IV) were immunohistochemically (IHC) analyzed for Patched (PTCH), Smoothened (SMO), and GLI1, GLI2 and GLI3 protein expression. Associations between Hedgehog protein expressions, clinicopathological factors, and clinical outcome data were examined.Results: Positive IHC staining for the five Hedgehog proteins was recorded in 8% to 37% of the tumor cells. The highest frequency was noted for SMO and the lowest for all. There was a significant association between low SMO- and GLI2-expression and KRAS-mutation. Tumors with overexpressed SMO had a higher frequency of residual tumor or local recurrences than tumors with low SMO expression. Patients with tumors expressing PTCH in more than 75% of the cells had significantly (P = 0.023) better recurrence-free survival than patients with tumors with low expression. The opposite situation was true for SMO. For GLI2, there was a statistically significant difference with regard to overall (P = 0.004) and distant (P = 0.015) relapse rate for groups with expression of GLI2 in the range of 5-25% compared to higher rates.Conclusions: A predictive and prognostic value was found for PTCH, SMO, and GLI2 with regard to residual carcinoma, local recurrences, and for GLI2 distant relapses. The Hedgehog signaling pathway also seems to play an important role in cervical carcinogenesis together with HPV16-infection and KRAS-mutation.
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| 5. |
- Bohr Mordhorst, Louise, 1958-, et al.
(författare)
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Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy
- 2016
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Ingår i: Oncotarget. - Orchard Park, USA : Impact Journals LLC. - 1949-2553. ; 7:39, s. 63042-63053
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Tidskriftsartikel (refereegranskat)abstract
- Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.
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