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  • 1.
    Bohr Mordhorst, Louise
    et al.
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy2014In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 135, no 2, p. 305-311Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Bohr Mordhorst, Louise
    et al.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, p. 63042-63053Article in journal (Refereed)
    Abstract [en]

    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.

  • 3. Clamp, A. R.
    et al.
    Mäenpää, J.
    Cruickshank, D.
    Ledermann, J.
    Wilkinson, P. M.
    Welch, R.
    Chan, S.
    Vasey, P.
    Sorbe, Bengt
    Örebro University, Department of Clinical Medicine.
    Hindley, A.
    Jayson, G. C.
    SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel-irinotecan as first-line therapy for ovarian cancer2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 1, p. 55-61Article in journal (Refereed)
    Abstract [en]

    The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.

  • 4.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Nygren, Lisa M. L.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Gustafsson, Anders O.
    Department of Biomedical Engineering, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt G.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Determination of the most effective cooling temperature for the prevention of chemotherapy‑induced alopecia2013In: Molecular And Clinical Oncology, ISSN 2049-9450, Vol. 1, no 6, p. 1065-1071Article in journal (Refereed)
    Abstract [en]

    Computer‑controlled scalp cooling to prevent alopecia is currently available for patients undergoing chemotherapy. Previous studies have suggested that the temperature should be <22˚C at a depth of 1‑2 mm in the scalp to prevent alopecia. However, the optimal pre‑set temperature of the coolant medium to achieve this temperature requires further investigation. A pre‑study was conducted to investigate which pre‑set coolant temperature of 3 and 8˚C was the most effective in achieving a scalp temperature of <22˚C. The temperature variations at different sites of the scalp and variations within and among the participants at baseline and during the cooling procedure were also evaluated. A randomized main study was then performed to compare the efficacy and side effects of the two temperature levels during paclitaxel/carboplatin chemotherapy. A group of 5 healthy female volunteers participated in a series of scalp temperature measurements during cooling with 3 and 8˚C of the coolant medium. In the randomized main study, a total of 47 patients were included, of whom 43 were evaluable after the first cycle. A pre‑set temperature of 3˚C tended to be the most efficient in achieving a hair follicle temperature of <22˚C. The top of the head was less responsive to scalp cooling. There were no significant differences in the prevention of alopecia between the two temperatures in the main study. However, headache and a feeling of coldness were more common in the 3˚C group. A coolant temperature of 3˚C was more effective in achieving a subcutaneous temperature of <22˚C. However, this finding was not reflected by a significant difference in the prevention of alopecia in this study, although a higher incidence of side effects was associated with a lower temperature level.

  • 5.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ternestedt, Britt-Marie
    Institutionen för vårdvetenskap, Ersta Sköndals Högskola, Stockholm.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Recurrence of ovarian cancer: living in limbo2007In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 30, no 4, p. 270-277Article in journal (Refereed)
    Abstract [en]

    Few studies have shed light on women's life situation after being informed of having recurrent ovanan cancer, The present study aimed to elucidate women's experiences of living with this knowledge. interviews were conducted with 12 women who were undergoing or had just completed chemotherapy, 5 to 10 months after learning or the recurrence. Data were collected and analyzed based on a life world perspective using a descriptive phenomenoiogical method. The women's experiences are described via 3 key constituents: being denied one's future while simultaneously hoping to be ble to delay the cancer's advancement, feeling alienated from both oneself and one's surroundings, and being responsible. The key constituents were integrated into the structure "living in limbo." The women lived on the threshoid to the unknown. They were preparing themselves both for a continued life and for death. "Living in limbo" can be described as a phase of a health-illness transition characterized by loneliness. The vulnerable position and existential struggle of these women should be focused upon in nursing. The sensitive dialogue is essential in these cases.

  • 6.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ternestedt, Britt-Marie
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Hallgren Graneheim, Ulla
    Patients' perceptions of communication with the health care team during chemotherapy for the first recurrence of ovarian cancer2011In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 15, no 1, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore what women with recurrent ovarian cancer perceived as important in their communication with the health care team. Method: Interviews were conducted with 12 women at the end of chemotherapy treatment at a department of gynecological oncology in central Sweden. The interviews were subjected to qualitative content analysis. Results: The findings stress the importance for the health care team to offer each woman the opportunity for support in becoming familiar with the disease. This theme of becoming familiar with the disease is underpinned by four sub-themes: being acknowledged as a unique person, getting help to make sense of information regarding the disease and its treatment, having the opportunity to be involved and to share responsibility, and feeling confident that medical expertise was adequate. Becoming familiar with the disease was expressed as a process of understanding and assimilating the whole new situation. To achieve familiarity, the women needed help from the health care team to make sense of the information they received. They stressed the importance of being able to influence encounters with health professionals, in accordance with their own perspectives. Being acknowledged as a unique person was a prerequisite to achieve familiarity. Also important to the women was having the opportunity to share responsibility for their care and lives with someone from the health care team. Conclusion: Helping women with recurrence of ovarian cancer attain a sense of familiarity with the disease should be an important priority for health care providers. (C) 2010 Elsevier Ltd. All rights reserved.

  • 7.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ternestedt, Britt-Marie
    Institutionen för vårdvetenskap, Ersta Sköndals Högskola, Stockholm.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Hällgren Graneheim, Ulla
    Insituionen för omvårdnad, Umeå universitet.
    Women's perceptions of interactions with the health care team during treatment of the first recurrence of ovarian cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Most women suffering a recurrence of ovarian cancer return to the same department where their primary cancer was treated. The aim of this study was to explore what women with the first recurrence of ovarian cancer perceived as important in their interaction with the healthcare team. Interviews were conducted with 12 women at the end of a chemotherapy treatment. The interviews were subjected to qualitative content analysis. The findings stress the importance for the healthcare team to offer each woman the opportunity to obtain support to become familiar with the disease. This theme of becoming familiar with the disease was supported by the following sub-themes: being confirmed as a person, getting help in making sense of information regarding the disease and its treatment, having the opportunity to be involved and share responsibility, and feeling confident that medical expertise is good enough.

    Becoming familiar with the disease was expressed as a process of understanding and assimilating the whole new situation. Optimal support from healthcare professionals was facilitated by establishing trusting relationships. Being confirmed and treated as a unique person was seen as a prerequisite to achieving familiarity with the disease. The women needed help to make sense of the information available. They stressed the importance of being able to influence their encounters with healthcare professionals in accordance with their own perspectives. Also of importance was having the opportunity to share the responsibility for their care and lives. The findings suggest that patients’ need should be identified repeatedly throughout the illness trajectory.

  • 8.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ternestedt, Britt-Marie
    Department of Palliative Care Research, Ersta Sköndal University College, Stockholm, Sweden; Department of Neurobiology, Caring Sciences and Society, Karolinska Institute, Stockholm, Sweden; Research and Development Department, Stockholms Sjukhem Foundation, Stockholm, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Gynaecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sunvisson, Helena
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Neurological Medicine, Örebro University Hospital, Örebro, Sweden.
    Lived experiences of women with recurring ovarian cancer2014In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 18, no 1, p. 104-109Article in journal (Refereed)
    Abstract [en]

    Background: Women with recurring ovarian cancer are living longer, due to advances in treatment options. They are now often outpatients, experiencing rapid encounters on treatment days. Whether this shift in care meets women’s needs has been scarcely explored scientifically.

    Purpose of the study: This study aimed to illuminate the phenomenon of living with recurring ovarian cancer as experienced by women in that condition.

    Methods and sample: A descriptive phenomenological method was used. Eight open-ended interviews with four women were performed approximately three and five years after the first recurrence of ovarian cancer. During these years the women had repeated clinically and radiologically verified recurrence requiring chemotherapy.

    Key results:The phenomenon of living with recurring ovarian cancer meant that the women felt forced to pay attention to the failing body in order to avoid a potential breakdown. The growing limitation of their intermittent strength meant that strength had to be captured and protected. Sharing their lives with others was difficult, due to the different living conditions. The women found no space to mediate their experiences, either in close relationships or with health care professionals. But, the circumstances they lived under also generated a gratitude for the unexpected extra time.

    Conclusions: The findings revealed that the four women were grateful to live a while longer, but needed to share their state of being. The findings are indeed directed to health care professionals, who need to provide a more patient-centred care to meet the women’s needs.

  • 9.
    Ekwall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ternestedt, Britt-Marie
    Institutionen för vårdvetenskap, Ersta Sköndals Högskola, Stockholm.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Sunvisson, Helena
    Örebro University, School of Health and Medical Sciences.
    The lived experience of life-prolonging treatment of recurring ovarian cancerManuscript (preprint) (Other academic)
    Abstract [en]

    There has been an improvement in the effectiveness of chemotherapy agents to restrain recurring ovarian cancer, such that women live with the disease for longer than they used to. However, there is a knowledge gap concerning how patients define their world from a lifeworld perspective, when living with life-prolonging treatment. The aim of the study was to illuminate the phenomenon of living with life-prolonging treatment of recurring ovarian cancer. Four women were interviewed twice, once in 2003, three years after the first recurrence, and again in 2005. The method was based on Giorgi’s phenomenological method. A situated structure for each woman was followed by a transformation into a general structure for all women, which communicates the most invariant meaning of the phenomenon.

    The general structure showed the growing threat to the women’s existence and their perception that time was short, yet extendable. Awareness of life’s limitedness evoked gratitude for the possibility to postpone death. The body’s strength was increasingly fragile and jeopardized the restraining of the disease. The amount of strength available was unpredictable, which meant a break in the rhythm of everyday life. Strength had to be captured and cared for.

    The wish to share the meaning of the disease with others was expressed as unattainable. The women were unable to realize the desire to be seen as an example of someone living with ongoing treatments. In encounters with other people, the cancer-afflicted body stood out as a barrier to communication. Inability to share their experience was also manifested in the women’s encounters with caregivers, which were characterized by an objective attitude. The women met with a gradual compliance their caregivers’ inability to respond to them.

  • 10.
    Ekwall, Ewa
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ternestedt, Britt-Marie
    Institutionen för vårdvetenskap, Ersta Sköndals Högskola, Stockholm.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Important aspects of health care for women with gynecologic cancer2003In: Oncology Nursing Forum, ISSN 0190-535X, E-ISSN 1538-0688, Vol. 30, no 2, p. 313-319Article in journal (Refereed)
    Abstract [en]

    Purpose/Objectives: To describe what women diagnosed with primary gynecologic cancer reported to be important during their interacion with the healthcare system.

    Design: Qualitative.

    Setting: A specialized gynecologic cancer care unit in central Sweden.

    Sample: 14 women diagnosed with primary gynecologic cancer were recruited. The women had been referred to the specialized care unit for radiation or cytostatic therapy.

    Methods: Tape-recorded interviews were transcnbed, coded, categoized, and analyzed.

    Main Research Variables: Primary diagnosed women with cancer and their experience with quality of care during diagnosis and treatment.

    Findings: Three partly overlapping categories (i.e., optima! care,good communication, and self-image and sexuality) were found to be of central importance in quality of health care. Participants stated that health care should be based on their own perceptions of the need for information and dialogue and how the disease and treatment would affect their health, self-image, and sexuality. Everyday conversations also were very important.

    Conclusions: Central importance in health care for the women included both rational and human aspects. The primary need of participants was available, competent, and coordinated.

    Implications for Nursing: Women with gynecologic cancer should be given individualized information and care to satisfy their individual needs and reinforce their self-image. Nurses have an important role in strengthening women´s  feelings of hope and supporting them in maintaining as positive a self-image as possible. Information and everyday conversation are of great significance. Sexuality should be an integral part of holistic care; to this end, inclusion of each woman's sexual partner may be helpful when discussions concerning sexuality occur.

  • 11.
    Farkas, Sanja A.
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt G.
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Epigenetic changes as prognostic predictors in endometrial carcinomas2017In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 12, no 1, p. 19-26Article in journal (Refereed)
    Abstract [en]

    Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31 and n = 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.

  • 12.
    Graflund, M.
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sigurdardóttir, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    HPV-DNA, vascular space invasion, and their impact on the clinical outcome in early-stage cervical carcinomas2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 14, no 5, p. 896-902Article in journal (Refereed)
    Abstract [en]

    The present study was designed to analyze the relationship of human papillomavirus (HPV)-DNA, microvessel density, and their impact on clinical outcome in early cervical carcinoma. HPV-DNA was evaluated in 171 cases of cervical carcinoma treated from 1965 to 1990. In 110 cases, the analyses could be performed. A polymerase chain reaction technique was used on paraffin-embedded specimens obtained before the start of therapy. HPV-DNA of any type was detected in 78% (86/110) of all evaluable tumors. HPV16 was the predominant type and was detected in 56% (62/110), HPV18 in 8% (9/110), and HPV35 in 21% (23/110). Patients with tumors containing HPV16 or HPV18 were significantly (P = 0.011) younger than patients with tumors not containing either of these two subtypes. Vascular space invasion and lymph node metastases were observed more frequently in tumors expressing HPV16 and HPV18 (P = 0.002, P = 0.047) than in tumors negative for these HPV strains. Tumors containing HPV16 and HPV18 were significantly (P = 0.012) larger and more frequently (P = 0.005) associated with higher FIGO stages. The cancer-specific survival rate was lower for patients with HPV16- and HPV18-positive tumors, but the difference was not statistically significant. The microvessel density was a non-significant prognostic factor. The overall 5-year survival rate of the complete series was 91%. It was concluded that HPV-DNA was a prognostic factor in early-stage cervical cancer and was associated with the age of the patient, vascular space invasion, lymph node metastases, tumor size, and FIGO stage.

  • 13.
    Graflund, M.
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sigurdardóttir, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma: correlation with clinical outcome2004In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 12, no 1, p. 169-176Article in journal (Refereed)
    Abstract [en]

    The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.

  • 14.
    Graflund, Marianne
    et al.
    Departments of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Departments of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Bryne, M.
    Department of Pathology, Institute of Cancer Research, Norwegian Radium Hospital, Oslo, Norway.
    Karlsson, Mats G.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    The prognostic value of a histologic grading system, DNA profile, and MIB-1 expression in early stages of cervical squamous cell carcinomas2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 2, p. 149-157Article in journal (Refereed)
    Abstract [en]

    This study evaluated the prognostic importance of a new grading system focusing on the invasive tumor front, DNA profile, and the proliferation marker MIB-1. A complete geographic series of 172 women treated with radical hysterectomy (Wertheim-Meigs) for FIGO stage I-II cervical carcinomas was the target population. The analyses were performed on 141 (82%) squamous cell carcinomas of the complete series. During the period of observation (mean 222 months), 17 recurrences (12.1%) were encountered. Prognostic factors for disease-free survival were lymph node status (P < 0.000001), radical surgical margins (P = 0.00004), and tumor size (P = 0.002). The complete score of the invasive front grading system (IFG), and the individual scores of two variables-pattern of invasion and host response-were all significantly (P = 0.002, P = 0.007, P = 0.0001) associated with pelvic lymph node metastases. Host response was the single most important factor in the IFG system, and it was superior to the complete score in predicting lymph node metastases. The total IFG score was also a significant (P = 0.003) prognostic factor for disease-free survival. DNA ploidy, S-phase fraction, and MIB-1 expression were nonsignificant factors in predicting pelvic lymph node metastases and disease-free survival of the patient. The IFG in the original or modified versions could predict low- and high-risk groups of tumors and therefore be of value in treatment planning for these patients.

  • 15.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden .
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Hussein, A.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    Bryne, M.
    Department of Pathology, Institute of Cancer Research, the Norwegian Radium Hospital, Oslo, Norway.
    Karlsson, Mats G.
    Department of Pathology, Medical Center Hospital, Örebro, Sweden.
    The prognostic value of histopathologic grading parameters and microvessel density in patients with early squamous cell carcinoma of the uterine cervix2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 1, p. 32-41Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the prognostic importance of clinical and histopathologic factors, including malignancy grading systems (MGS), partial index (PI), invasive front grading (IFG), and microvessel density. A complete geographic series of 172 early stage (FIGO I-II) cervical carcinomas treated by Wertheim-Meigs surgery during the period 1965-1990 was studied. The patients were followed up for at least 10 years. Significant prognostic factors for disease-free survival were lymph node status (P < 0.0000001), radical surgical margins (P = 0.00003), and tumor size (P = 0.008). In a multivariate Cox analysis it was shown that lymph node status was the single most important prognostic factor with regard to disease-free survival. The total MGS and the PI scores were highly significantly (P = 0.0001) associated with pelvic lymph node metastases and disease-free survival rate in squamous cell carcinomas. The MGS and the PI systems were superior to the IFG system in predicting lymph node metastases. The total IFG score was also a statistically highly significant (P = 0.003) prognostic factor with regard to disease-free survival in both univariate and multivariate analyses. Microvessel density was a nonsignificant prognostic factor. There was a highly significant (P = 0.002) association between vascular space invasion of tumor cells and the presence of lymph node metastases. In conclusion, histopathologic malignancy grading systems provide valuable prognostic information in patients with early stage squamous cell carcinomas of the uterine cervix.

  • 16.
    Graflund, Marianne
    et al.
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Immunohistochemical expression of p53, bcl-2, and p21(WAF1/CIP1) in early cervical carcinoma: correlation with clinical outcome2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 3, p. 290-298Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to assess the value of p53, bcl-2, and p21(WAF1/CIP1) immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21(WAF1/CIP1). None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21(WAF1/CIP1) appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.

  • 17.
    Graflund, Marianne
    et al.
    Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G
    Örebro University Hospital, Örebro, Sweden.
    MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: correlation with clinical outcome2002In: International Journal of Oncology, ISSN 1019-6439, Vol. 20, no 5, p. 1041-1047Article in journal (Refereed)
    Abstract [en]

    A complete series of 40 cervical carcinomas with pelvic lymph node metastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymph node metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and multivariate proportional hazard Cox analyses.

  • 18. Hallak, Sorana
    et al.
    Ladi, Luz
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Prophylactic inguinal-femoral irradiation as an alternative to primary lymphadenectomy in treatment of vulvar carcinoma2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 31, no 5, p. 1077-1085Article in journal (Refereed)
    Abstract [en]

    In a complete geographic series of 294 cases of primary vulvar carcinomas prophylactic inguinal-femoral irradiation was used as a standard postoperative therapy. Inguinal lymph node dissection was performed in only 27 cases (9%) and was not part of the standard surgery. The histology was squamous cell carcinoma in 269 cases (92%). The primary surgery was total vulvectomy, partial vulvectomy, or local resection of the tumor. The main type of radiotherapy was adjuvant inguinal irradiation. Two separate, symmetrical and rectangular inguinal fields were irradiated with combined photon and electron beams. In the complete series 127 recurrences (43%) were recorded. Local (24%) and regional recurrences (19%) were most frequent. Type of surgery was not associated with the risk of tumor recurrence. The 5-year overall survival rate was 53% and the relapse-free survival (RFS) rate was 55%. Tumor grade was significantly (P=0.007) associated with the RFS. The inguinal RFS rate was 75% both for patients treated with adjuvant inguinal irradiation without lymphadenectomy and patients treated with primary lymph adenectomy +/- inguinal irradiation. Postoperative complications were recorded in 22%. Postoperative complications occurred most frequently in the subgroup undergoing inguinal lymphadenectomy. Chronic lymph edemas were the most serious late tissue reactions.

  • 19. Högberg, Thomas
    et al.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Åvall-Lundqvist, Elisabeth
    Gynekologisk onkologi2008In: Onkologi / [ed] Ulrik Ringborg, Tina Dalianis, Roger Henriksson, Stockholm: Liber , 2008, 2, p. 488-533Chapter in book (Other academic)
  • 20.
    Isaksson, Helena S.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences/Clinical Chemistry, Umeå University, Umeå, Sweden.
    Whole genome expression profiling of blood cells in ovarian cancer patients: prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14 genes2014In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 5, no 12, p. 4040-4049Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well-to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

  • 21.
    Karlsson, Johannes
    et al.
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Dreifaldt, Ann-Charlotte
    Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Bohr Mordhorst, Louise
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health Sciences. Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Differences in outcome for cervical cancer patients treated with or without brachytherapy2017In: Brachytherapy, ISSN 1538-4721, E-ISSN 1873-1449, Vol. 16, no 1, p. 133-140Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    Lillsunde Larsson, Gabriella
    et al.
    Örebro University, School of Health Sciences. Department of Laboratory Medicine.
    Kaliff, Malin
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Sorbe, Bengt
    Örebro University, School of Health Sciences. Department of Oncology.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma2018In: Papillomavirus research, ISSN 2405-8521, Vol. 6, p. 63-69Article in journal (Refereed)
    Abstract [en]

    Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype.

    The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation.

    In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors.

    The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma.

  • 23.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital, Örebro, Sweden.
    Elgh, Fredrik
    Umeå University Hospital, Umeå, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University Hospital, Örebro, Sweden.
    Human Papillomavirus (HPV) and HPV 16-Variant Distribution in Vulvar Squamous Cell Carcinoma in Sweden2012In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 22, no 8, p. 1413-1419Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the human papillomavirus (HPV) and HPV type 16-variant distribution in a series of vulvar squamous cell carcinomas (VSCC) and to evaluate the impact of HPV and HPV 16-variant on prognosis.

    Methods: A series of 133 patients who had a diagnosis of VSCC (1983-2008) was selected for the study. Detection of 11 high-risk HPV types (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59) and 2 low-risk HPV types (6 and 11) was performed with real-time polymerase chain reaction. Samples positive for HPV 16 were further analyzed for variant determination of 7 positions in the E6 gene with polymerase chain reaction and pyrosequencing.

    Results: Forty (30.8%) of 130 tumors were found to be HPV positive. Human papillomavirus type 16 was found in 31 cases, HPV 18 was found in 2 cases, HPV 33 was found in 5 cases, and HPV 56 and HPV 59 were found in one case each. All but one tumor harboring HPV 16 were of European linage, and the 3 most common variants were E-p (n = 13), E-G350 (n = 7), and E-G131 (n = 5). HPV positivity was associated with the basaloid tumor type and occurred in significantly younger patients. Overall and recurrence-free survival rates were better in HPV-positive cases, but after correction for age and tumor size, HPV status was no longer an independent and significant prognostic factor. The survival rates of the various HPV 16 variants were not significantly different, but there was a trend of worse outcome for the E-G131-variant group.

    Conclusions: Human papillomavirus positivity of 30.8% is similar to other reports on VSCC. To our knowledge, this first variant determination of HPV 16 in vulvar carcinoma in a Swedish cohort indicated that the variant E-G131 may have an increased oncogenic potential in patients with VSCC.

  • 24.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Helenius, Gisela
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Andersson, Sören
    Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma2013In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 129, no 2, p. 406-411Article in journal (Refereed)
    Abstract [en]

    Objective

    The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis.

    Methods

    Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing.

    Results

    53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3341; p = 0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p = 0.0002; p = 0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate.

    Conclusions

    HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis.

  • 25.
    Lillsunde-Larsson, Gabriella
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Viral Load, Integration and Methylation of E2BS3 and 4 in Human Papilloma Virus (HPV) 16-Positive Vaginal and Vulvar Carcinomas2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, article id e112839Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact.

    Methods: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing.

    Results: Vaginal tumors were found to have a higher viral load (p=0.024) compared to vulvar tumors but a high copy number (> median value, 15 000) as well as high methylation (> 50%) was significantly (p=0.010 and p=0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150 000 copies not highly methylated (n=25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n=6, 11.1%); (3) tumors with viral DNA fully integrated (n=11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium-or unmethylated (< 50%) and having a high viral load (> total mean value 150 000; n=12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed.

    Conclusion: HPV16-related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16-related parameters were found to be of clinical importance in the vulvar series only.

  • 26. Löf-Ohlin, Zarah M.
    et al.
    Sorbe, Bengt
    Wingren, Sten
    Örebro University, School of Health and Medical Sciences.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Hypermethylation of promoter regions of the APC1A and p16(INK4a) genes in relation to prognosis and tumor characteristics in cervical cancer patients2011In: International Journal of Oncology, ISSN 1019-6439, Vol. 39, no 3, p. 683-688Article in journal (Refereed)
    Abstract [en]

    Hypermethylation of the O(6)-MGMT, p14(ARF), p16(INK4a), RASSFIA and APC1A genes are unfavourable prognostic markers in colorectal cancer (CRC). We hypothesized that they could be related to prognosis also in cervical cancer. Methylation was studied in DNA extracts from surgical specimens of cancer tissue by novel pyrosequencing methods. In 109 patients (90 squamous cell carcinomas, 19 adenocarcinomas), we found that hypermethylation of the APC1A gene promoter occurred in 8.3% of patients, and of p16(INK4a) in 1.8%. APC1A hypermethylation was significantly related to more advanced FIGO stage of the tumor (P=0.013), larger tumor diameter (P=0.049) and distant recurrence-free survival (P=0.0007), but not with locoregional recurrence rate, age, HPV status, DNA ploidy, tumor grade or malignancy grading score. We conclude that methylation of the APC1A promoter in cervical cancer, as diagnosed by pyrosequencing, is significantly related to major biological characteristics of the tumor, and may be a new predictor of poor prognosis in cervical cancer.

  • 27. Löf-Öhlin, Zarah M.
    et al.
    Levanat, Sonja
    Sabol, Maja
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Promoter methylation in the PTCH gene in cervical epithelial cancer and ovarian cancer tissue as studied by eight novel Pyrosequencing (R) assays2011In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 3, p. 685-692Article in journal (Refereed)
    Abstract [en]

    DNA methylation status in the CpG sites of promoter regions in cancer-related genes, such as PTCH, has traditionally been investigated using either dye-terminator sequencing or methylation-specific PCR. We aimed to study the PTCH gene promoter methylation in gynecological cancers with a method that gives a quantitative measure of the methylation status of the promoter region of the studied gene, and for this purpose, we designed novel Pyrosequencing-based assays. Bisulfite-treated genomic DNA (bsDNA) was amplified by standard PCR and applied to novel Pyrosequencing(R) assays, in order to measure the methylated fraction (%) at each CpG site of the PTCH gene promoter. We analyzed 22 squamous cell cervical cancer tissue specimens (11 with good and 11 with poor outcomes after radiotherapy) and 5 ovarian cancer tissue specimens matched with 5 normal ovarian tissue specimens. Six optimized PCR protocols which generated 8 Pyrosequencing assays covering 63 CpG sites in the promoter regions 1 and 2 as well as the previously unanalyzed promoter region 3 in the PTCH gene were developed. The 27 tumor tissue specimens and 5 normal tissues did not show any methylation within any of the 63 CpG sites. Our data suggest that methylation of the PTCH promoter is not a high-prevalence feature of squamous cell cervical cancer or ovarian cancer, but Pyrosequencing assays are a good method for studying promoter methylation.

  • 28.
    Mordhorst, Louise Bohr
    et al.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Leif
    Department of Radiation Physics, Örebro University Hospital, Örebro, Sweden.
    Bärmark, Berit
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Combined External and Intracavitary Irradiation in Treatment of Advanced Cervical Carcinomas Predictive Factors for Treatment Outcome and Early and Late Radiation Reactions2014In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 24, no 7, p. 1268-1275Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of this study was to find out predictive factors of tumor control as well as acute and late radiation reactions in treatment of advanced cervical carcinomas.

    Methods: In a series of 134 primary cervical carcinomas in International Federation of Gynecology and Obstetrics stages I to IV treated with combined external pelvic and intraluminal cervical-vaginal brachytherapy, predictive and prognostic factors were analyzed with regard to tumor control, recurrences, survival data, and adverse effects. Concomitant chemotherapy was given to 48 patients (35.8%). The external beam therapy was given with a 4-field technique (50-60 Gy) and brachytherapy was given with a high-dose rate (iridium-192) afterloading technique using a ring applicator set. A computed tomographically based 3-dimensional dose-planning system was used for the external beam therapy and for the brachytherapy planning. The mean age of the patients was 65 years. A total of 110 tumors were squamous cell carcinomas and 24 were adenocarcinomas or adenosquamous carcinomas. A total of 111 tumors were in International Federation of Gynecology and Obstetrics stages I to II; 23 tumors, in stages III to IV.

    Results: The primary control rate of the complete series was 92.5%. Tumor size, the brachytherapy dose, the combined external and brachytherapy dose, as well as the number of days of interruption (delay) of irradiation were all significant predictive factors for local tumor control. Forty recurrences (30%) were recorded. Early radiation reactions were recorded in 67% (mostly grade 1) and were associated with the widths of the anterior-posterior and lateral pelvic fields. Serious late radiations reactions (grade 3-4) were noted in 11%.

    Conclusions: The width of the lateral pelvic fields, left point A and B doses, dose to the rectal reference point, as well as asymmetry of the dose distribution were associated with late severe reactions. Prior abdominal and pelvic surgery was also a high-risk factor for late tissue reactions. Concomitant chemotherapy did not increase the risk for acute or late toxicity.

  • 29.
    Qvick, Alvida
    et al.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Sorbe, Bengt
    Örebro University Hospital. Örebro University, School of Health Sciences. Department of Oncology.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Lillsunde Larsson, Gabriella
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?2017In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 34, no 3, article id 36Article in journal (Refereed)
    Abstract [en]

    Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.

  • 30.
    Ranhem, Cecilia
    et al.
    Department of Women’s and Children ’s Health, Karolinska Institutet, Stockholm, Sweden; Centre for Clinical Research, Hospital of Västmanland Västerås, Uppsala University, Västerås, Sweden; Region Västmanland, Västerås, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hedman, Håkan
    Department of Radiation Sciences, Umeå University, Umeå , Sweden.
    Lindquist, David
    Department of Radiation Sciences, Umeå University, Umeå , Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hellström, Ann-Cathrin
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Östensson, Ellinor
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidem iology and Biostatistics, Karolinsk a Institutet, Stockholm, Sweden.
    Sorbe, Bengt
    Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hellman, Kristina
    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sonia
    Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 8, article id e0183816Article in journal (Refereed)
    Abstract [en]

    Background: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients.

    Methods: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses.

    Results: The majority of PVC patients (72%) had > 50% LRIG1-and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival.

    Conclusion: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.

  • 31. Skirnisdottir, Ingiridur
    et al.
    Lindborg, Katarina
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Adjuvant chemotherapy with carboplatin and taxane compared with single drug carboplatin in early stage epithelial ovarian carcinoma2007In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 18, no 5, p. 1249-1256Article in journal (Refereed)
    Abstract [en]

    The objective of the present study was to compare recurrence-free survival (RFS) in early stages (FIGO stages I-II) of epithelial ovarian cancer after adjuvant chemotherapy with carboplatin and a taxane (113 patients) and with carboplatin alone (27 patients). The distribution of clinical and pathological prognostic factors as well as type of primary surgery were comparable in the two groups. Recurrence rate was 21% and RFS was 79% in the series of patients treated with taxane-based chemotherapy and 19% and 81%, respectively, in the series of patients who received single drug carboplatin. Thus, no significant differences were recorded. The major toxicities in the present study were myelosuppression (46%) and neuro-toxicity (26%). Neurotoxicity was more frequently (P=0.007) recorded and of higher grade (P=0.011) for patients in the carboplatin-taxane series compared with patients in the carboplatin series. RFS for patients in FIGO-stage I was 85% and for patients in FIGOstage II only 47%. In a multivariate logistic regression analysis of predictive factors for tumor recurrence in the complete series (n=140) the FIGO stage was the only independent and significant (P=0.0006) predictive factor with an odds ratio of 6.4 (95% CI: 2.2-18.9) for stage II versus IA-C. Age, tumor grade and type of adjuvant chemotherapy (± taxane) were not significant predictive factors. In the present study, although based on a limited number of patients, we could not find any improvement in recurrence rate or recurrence-free survival for patients treated with a carboplatin-taxane combination regimen compared with patients treated with carboplatin monotherapy. The spectrum of side effects was also in favor of the monotherapy regimen. Further, larger randomized studies are needed to give a final and fully conclusive answer to this question.

  • 32. Skirnisdottir, Ingiridur
    et al.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Prognostic factors for surgical outcome and survival in 447 women treated for advanced (FIGO stages III-IV) epithelial ovarian carcinoma2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 30, no 3, p. 727-734Article in journal (Refereed)
    Abstract [en]

    The objectives of this population-based, retrospective study, was to find predictive factors for surgical outcome and long-term survival in 447 patients with epithelial ovarian cancer in FIGO-stages III-IV treated during 1975-1993. The median overall survival rate of this series was 18 months, the 5-year cancer-specific survival rate was 18%, and the 5-year overall survival rate, 16%. In a logistic regression analysis, type of surgeon was the strongest (P=0.006) predictive factor for surgical outcome after the age of the patient. The optimal debulking rate was 36% for gynecologic oncologists, 29% for general gynecologists, 24% for combined gynecologist and obstetrician with the third level of specialization, and 4% for general surgeons. Optimal debulking (no visible tumor or residual tumor <2 cm) was achieved in 26% of the cases. Predictive factors of the outcome of cytoreduction were FIGO-stage (P=0.007), histological subtype (P=0.016), and tumor grade (P=0.046) in univariate analyses. In a Cox multivariate analysis the most important prognostic factor for overall survival was the amount of residual cancer (P=0.000001) before age, grade and stage. Therefore, to achieve optimal surgical outcome and optimal overall survival rate the primary surgery of advanced ovarian cancer should be performed by gynecologic oncologists or by gynecologists specially trained in gynecologic cancer surgery.

  • 33. Skirnisdottir, Ingiridur
    et al.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Prognostic impact of body mass index and effect of overweight and obesity on surgical and adjuvant treatment in early-stage epithelial ovarian cancer2008In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 18, no 2, p. 345-351Article in journal (Refereed)
    Abstract [en]

    The present study was performed to find out if the body mass index (BMI) was associated with clinical and pathologic features (age, histology, tumor grade, and substages) and prognosis in early stages (FIGO I–II) of epithelial ovarian cancer. Further aims of the study were to evaluate if overweight or obesity affected the feasibility of optimal surgery and postoperative adjuvant therapy. A total of 635 patients were included in this study. Four percent of the patients were underweight (BMI <18.5), 53% were of ideal body weight (BMI 18.5–25), 31% were overweight (BMI 25–30), and 12% were obese (BMI >30). Overweight and obese patients were significantly (P = 0.006) older than underweight and ideal body weight patients. Tumor grade and histologic type distributions were not different across the BMI strata. FIGO stage (P = 0.011) and presence of ascites (P = 0.007) at primary surgery were associated with the BMI status. A history of cardiovascular disease was significantly (P = 0.006) more common in overweight and obese patients. Survival analyses in the four BMI subgroups did not show any significant differences with regard to recurrence-free survival. The 5-year recurrence-free survival of the complete series was 72%. Overweight and obese patients did not have worse survival than normal weight and underweight patients. Perioperative or postoperative morbidity and adjuvant oncologic treatment were not affected by the BMI. In a multivariate Cox analysis, FIGO substage and tumor grade, but not BMI, were independent and significant prognostic factors with regard to all types of survival rates.

  • 34. Skirnisdottir, Ingiridur
    et al.
    Sorbe, Bengt
    Örebro University, School of Health and Medical Sciences.
    Survival and prognostic factors in early-stage epithelial ovarian carcinoma treated with taxane-based adjuvant chemotherapy2007In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 17, no 6, p. 1231-1237Article in journal (Refereed)
    Abstract [en]

    The present study was undertaken with the question about the outcome (recurrence-free survival, [RFS]) after adjuvant chemotherapy with taxane and carboplatin in the early stages of epithelial ovarian cancer after primary surgery. Treatment-related toxicity was also evaluated. A total of 113 patients were included in this study. The 5-year RFS rate for all 113 patients treated with adjuvant chemotherapy including taxane and carboplatin after primary surgery was 79%. The 5-year RFS rate for 85 patients in FIGO stage I was 85% and for 18 patients in FIGO stage II, it was 44%. For clear-cell carcinomas, the RFS was 87%. In univariate analysis, recurrent disease was associated with both FIGO stage and tumor grade, but in multivariate logistic regression analysis of prognostic factors for tumor recurrences, only FIGO stage (stage I versus stage II) was a significant and independent prognostic factor. However, an odds ratio (OR) of 1.9 for tumor grade (grade 3 versus grades 1–2) demonstrated two times increased risk for recurrence in a patient with a grade 3 tumor compared with grade 1–2 tumors. Furthermore, an OR of 0.39 for lymph node sampling versus no sampling meant 61% reduced risk for recurrence for a patient who had undergone lymph node sampling at surgical staging laparotomy. The major toxicities in the present study were myelosuppression (46%) and neurotoxicity (34%). Despite the use of prophylaxis, severe paclitaxel-related hypersensitivity occurred in three patients (3%).

  • 35.
    Sorbe, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Andersson, H
    Boman, K
    Rosenberg, P
    Kalling, M
    Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up2008In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 18, no 4, p. 803-808Article in journal (Refereed)
    Abstract [en]

    There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma. Cisplatin and doxorubicin with or without cyclophosphamide are widely used. Response rates have improved with combination chemotherapy compared with single-agent therapy. A platinum analog seems to be an important part of the chemotherapy regimen. Since few patients are cured from their disease and since the duration of response is short, further improvement of this therapy is warranted. During the past years, the taxanes (paclitaxel) are being added to prior evaluated regimens and not only improved response rates are reported but also increased toxicity is observed. In a prospective, phase II, multicenter study, carboplatin (area under the curve = 5) and paclitaxel (175 mg/m(2)) were evaluated in treatment of primary advanced and recurrent endometrial carcinoma. In total, 66 patients were recruited during the years 2000-2004. Eighteen primary advanced tumors and 48 recurrences were treated. All histologic types and tumor grades were allowed. The median follow-up was 57 months (range 37-69 months). The overall response rate was 67% (95% CI 55-78). The complete response rate was 29% and the partial response rate 38%. Primary advanced and recurrent tumors as well as endometrioid and nonendometrioid tumors showed similar response rates. The median response duration was 14 months. The 1- and 3-year survival rates were 82% and 33%, respectively. The main toxicities were hematologic and neurologic (sensory neuropathy). The response rates were encouraging, superior to prior platinum-containing regimens, but response duration and the long-term survival rate were still short. The neurologic toxicity was frequent and was a substantial problem in this series of patients. Further research is highly needed to improve the treatment of advanced and recurrent endometrial cancer.

  • 36.
    Sorbe, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Johansson, Birgit
    Prophylactic pelvic irradiation as part of primary therapy in uterine sarcomas2008In: International Journal of Oncology, ISSN 1019-6439, Vol. 32, no 5, p. 1111-1117Article in journal (Refereed)
    Abstract [en]

    In a complete geographic series of 155 cases of primary uterine sarcomas, prophylactic pelvic irradiation was used as standard postoperative therapy in the majority of the cases. Vaginal brachytherapy was also added as a boost. The histology was leiomyosarcoma in 62 cases (40%), carcinosarcoma in 60 (39%), endometrial stromal sarcoma in 25 (16%), and other types in 8 cases (5%). The primary surgery was extended hysterectomy in 11 cases (7%), simple hysterectomy in 110 (71%), and supravaginal hysterectomy in 12 (8%). In 22 cases (14%) no major surgery was possible. In the complete series, 62 recurrences (40%) were recorded. Local (9%), regional (9%), and distant recurrences (28%) were the most frequent. The type of surgery was associated with the risk of tumor recurrence. Extended surgery reduced the risk of local and regional recurrences. The 5-year overall survival rate was 42% and the recurrence-free survival (RFS) was 37%. The number of mitoses was significantly (P=0.007) associated with survival. The locoregional RFS rate was 75% for patients treated with adjuvant irradiation and 83% for patients treated with primary surgery alone. Serious late tissue reactions from the bladder and intestine occurred in 7% of the irradiated cases. The locoregional tumor control rate was high in this series of patients, but no significant difference was found between patients treated with surgery alone and surgery plus postoperative pelvic irradiation. This was true for all histological subtypes of the uterine sarcomas. However, this was not a randomized study and selection bias cannot be ruled out

  • 37.
    Sorbe, Bengt
    et al.
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Juresta, Christian
    Department of Obstetrics and Gynecology, University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, University Hospital, Örebro, Sweden.
    Natural history of recurrences in endometrial carcinoma2014In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, p. 1800-1806Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the natural history of endometrial cancer recurrences with regard to predictive and prognostic factors. Between 1990 and 1999, 100 patients were treated for recurrences of endometrial carcinoma (all FIGO stages). Overall, 90 tumors were of endometrioid type. A total of 82 patients were treated with surgery, 41 patients received adjuvant external irradiation and 91 patients received vaginal brachytherapy. The median time to recurrence (TTR) was 32 months. The recurrences were treated using a combination of high-dose-rate brachytherapy and external pelvic irradiation in 35 cases. In addition, 44 patients were treated with chemotherapy and 21 patients received other types of therapy. The complete remission rate was 29% and the overall response rate was 44%. Among patients treated with radiotherapy, the response rate was 88% and, for those treated with chemotherapy, the rate was 33%. The local control of vaginal recurrences treated with combined radiotherapy was 93%. In 45 patients (45%) a second recurrence was identified and a third recurrence occurred in 12 patients. The overall five-year survival rate was 44%. Age, FIGO grade, nuclear grade, TTR and response to treatment were found to be independent and significant prognostic factors for overall survival rate. Locoregional recurrences were associated with a generalized extra-pelvic disease in 63% of the cases.

  • 38.
    Sorbe, Bengt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Nordström, Britta
    Mäenpää, Johanna
    Kuhelj, Janez
    Kuhelj, Dimitrij
    Okkan, Sait
    Delaloye, Jean-Francois
    Frankendal, B.
    Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer: a controlled randomized study2009In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 19, no 5, p. 873-878Article in journal (Refereed)
    Abstract [en]

    The purpose of the study was to compare postoperative vaginal irradiation with surgery alone in low-risk International Federation of Gynecology and Obstetrics (FIGO) stage IA-IB endometrial carcinoma. The study was a prospective, randomized trial of 645 evaluable low-risk endometrial carcinoma patients from 6 European gynecologic cancer centers. All tumors were in FIGO stage IA-IB, of endometrioid histological type, and FIGO grade 1-2. High-dose-rate afterloading equipments (iridium [Ir] 192 or cobalt [co] 60) were used at 5 centers, and low-dose-rate (LDR) afterloading equipment (cesium [Cs] 137) at 1 center. Perspex vaginal applicators or ovoids were normally used, and the dose was specified at 5 mm from the surface of the applicator. Three to 6 fractions (3.0-8.0 Gy) were given, and the overall treatment time was 4 to 15 days. A total of 319 patients were treated with surgery plus vaginal irradiation (treatment group), and 326 patients with surgery alone (control group).Twenty-six recurrences (4.0%) were recorded in the complete series. The locoregional recurrence rate was 2.6%, whereas distant metastases occurred in 1.4%. The rate of vaginal recurrences was 1.2% in the treatment group versus 3.1% in the control group. The difference was not statistically significant (P = 0.114). Side effects were few and mild (grade 1-2). Dysuria, frequency, and incontinence were slightly more common after vaginal irradiation (2.8% vs 0.6%, respectively). Late intestinal problems were few and similar in the 2 groups. The conclusions were that the impact of postoperative brachytherapy on even the locoregional recurrence rate seems to be limited in patients with low-risk endometrial carcinoma. The overall recurrence rate and survival were similar in the 2 groups.

  • 39.
    Sorbe, Bengt
    et al.
    Örebro University Hospital. Dept Oncol.
    Paulsson, Gunnar
    Dept Gynecol & Obstet, Cent Hosp Skövde, Skövde, Sweden.
    Andersson, Solveig
    Dept Gynecol & Obstet, Mälarsjukhuset, Eskilstuna, Sweden.
    Steineck, Gunnar
    Dept Clin Canc Epidemiol,Inst Clin Sci,Dept Oncol, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    A population-based series of uterine carcinosarcomas with long-term follow-up2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 759-766Article in journal (Refereed)
    Abstract [en]

    Background. Carcinosarcomas are a highly malignant type of endometrial carcinomas where extra uterine spread and recurrences are frequent. There is no consensus regarding the best treatment of this group of malignancies. Material and methods. In a complete geographic series of 322 cases of primary uterine carcinosarcomas prophylactic pelvic irradiation and/or chemotherapy was used as postoperative treatment in the majority of the cases. Vaginal brachytherapy was also added as a boost. The primary surgery was extended hysterectomy in 23 cases (10%), and simple hysterectomy in 220 cases (90%). In 46 cases (14%) no major surgery was possible. Results. In the complete series 123 recurrences (38%) were recorded. Locoregional recurrences (11%) and distant recurrences (28%) were most frequent. Type and extent of surgery was not associated with the risk of tumor recurrence. Extended surgery did not reduce the risk of local and regional recurrences. In the complete series, the five-year overall survival rate was 30% and the recurrence-free survival (RFS) rate was 27%. The five-year pelvic disease control was 82% in stage I, 68% in stage II, and 76% for more advanced stages. The five-year locoregional RFS rate was 63% for patients treated with surgery alone, 68% after addition of adjuvant chemotherapy, 86% after adjuvant radiotherapy, and 95% after combined chemotherapy and radiotherapy. Conclusion. Radiotherapy seems to be the most important constituent of the adjuvant therapy. Serious late tissue reactions, requiring surgery, from the bladder and intestine occurred in 2.5% of the irradiated cases. The death of three patients could be related to radiotherapy and of four patients due to the cytotoxic treatment. This population-based series may serve as a baseline for improvements by, e. g. standard care programs and referral to a few specialist centers for this rare and serious disease.

  • 40.
    Wegman [Palmebäck-Wegman], Pia
    et al.
    Örebro University, School of Health and Medical Sciences.
    Ahlin, Cecilia
    Sorbe, Bengt
    Genetic alterations in the K-ras gene influence the prognosis in patients with cervical cancer treated by radiotherapy2011In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 21, no 1, p. 86-91Article in journal (Refereed)
    Abstract [en]

    Introduction: A high incidence of K-Ras mutations has been identified in a variety of human cancers, especially in codon 12, 13, and 61. Nevertheless, the presence of K-Ras mutations in cervical cancer remains controversial. The aim of this study was to investigate possible mutations in exon 1 and 2 of the K-Ras gene and to assess whether K-Ras mutation status had prognostic and predictive significance and were linked to clinicopathological parameters. Methods: Genomic DNA from 107 patients with cervical cancer, treated with radio-chemotherapy, were examined for mutations in the coding exons 1 and 2, including exon/intron borders of the K-Ras gene using single-stranded conformation polymorphism and sequence analyses. Results: K-Ras mutations were detected in 11 patients (10%). Seven tumors showed a mutation in codon 59, 3 tumors in codon 38, and 1 tumor in codon 13. In 6 of the cases with a mutation in codon 59, an additional alteration located in codon 65 was found. Patients with K-Ras mutations had significantly worse recurrence-free survival (P = 0.03), and an association between K-Ras status and distant metastases was also seen (P = 0.04). Conclusions: The present data indicate that K-Ras mutations are relatively uncommon in cervical cancer but associates with poorer prognosis, especially in the subset of squamous cell carcinomas. There is a need for new markers in cervical cancer to improve individual treatment, but whether K-Ras mutation status is a potential biomarker in this situation needs further investigations in larger tumor series and in more regions of the K-Ras gene.

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