Papers by Bengt Tholander
Background. With current standard‐dose chemotherapy ovarian cancer is a chemosensitive but not ch... more Background. With current standard‐dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first‐line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60–80%. However, only 10–20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high‐dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation.
Acta Oncologica
Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVS... more Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n ¼ 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR ¼ 5.46, CI 3.69-8.07, p < .001) followed by deep myometrial invasion (RR ¼ 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR ¼ 7.69, CI 2.03-29.10,) and non-diploidy (EMR ¼ 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n ¼ 404), only LVSI (HR ¼ 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.
Background The aim of this study was to analyze overall survival in endometrial cancer patients’ ... more Background The aim of this study was to analyze overall survival in endometrial cancer patients’ FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). Methods A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. Results In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18–1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95–1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. Conclusion The minima...
Journal of Clinical Oncology
14598 Background: Aflibercept, has demonstrated the ability to reduce formation of ascites in pre... more 14598 Background: Aflibercept, has demonstrated the ability to reduce formation of ascites in preclinical models of EOC, as well as in advanced EOC patients. Aflibercept, a potent angiogenesis inhibitor fusion protein, is comprised of portions of human vascular endothelial growth factor VEGF receptor R1+R2 (Flt-1, KDR) extracellular domains and fused to the Fc-portion of human IgG. Aflibercept binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. Methods: Aflibercept, 4 mg/kg, i.v. was administered every 2 weeks, in pts with advanced EOC and symptomatic ascites requiring frequent paracentesis (pct). Eligibility criteria included resistance to prior platinum based therapy and topotecan and/or liposomal doxorubicin, ECOG performance status of 0–2, normal organ function, no proteinuria (<500 mg/24 hrs or UPCR<1), controlled blood pressure, an average of <30 days between baseline pct. prior to study entry. Primary endpoint is Repeat Paracentesis Response Rate (RPRR), defined as at lea...
Acta Obstetricia Et Gynecologica Scandinavica
Background. With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not ch... more Background. With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first-line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60–80%. However, only 10–20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation.Methods. We report here our initial experiences of the use of high-dose chemotherapy supported by ASCT for patients with high-risk ovarian cancer. Two patients were treated at Uppsala University Hospital in 1992 and four patients at Turku University Central Hospital in 1994.Results. The first four patients treated either after heavy previous chemotherapy or recurrent disease relapsed within 5–10 months. Two patients received high-dose therapy as part of firstline treatment. One o...
Tumor markers for ovarian carcinoma : diagnostic and prognostic studies with emphasis on the CA-1... more Tumor markers for ovarian carcinoma : diagnostic and prognostic studies with emphasis on the CA-125 antigen
Acta Obstetricia et Gynecologica Scandinavica
Journal of Clinical Oncology
5017^ Background: In two randomized phase III trials in OC (GOG218 and ICON7), front-line BEV + q... more 5017^ Background: In two randomized phase III trials in OC (GOG218 and ICON7), front-line BEV + q3w PAC + q3w C followed by BEV alone significantly improved progression-free survival (PFS) vs chemotherapy (CT) alone. In the Japanese NOVEL trial, wPAC + q3w C was more effective than q3w PAC + C, but toxicity limited CT delivery. The single-arm OCTAVIA study evaluated front-line BEV + wPAC + q3w C. Methods: Patients (pts) received 6–8 cycles of BEV (7.5 mg/kg, d1) + wPAC (80 mg/m2 d1, 8, 15) + C (AUC6, d1) iv q3w, with BEV q3w continued alone for a total of up to 17 cycles (1 y) as front-line therapy for newly diagnosed OC (FIGO stage I–IIa [grade 3/clear cell] or stage IIb–IV [any grade]). The trial was designed to recruit a pt population similar to that enrolled in ICON7. The primary endpoint was PFS. Secondary endpoints included response rate, duration of response, overall survival, biological progression-free interval, and safety. Previously we reported safety findings from the co...
International Journal of Cancer
Acta Oncologica
Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer stagi... more Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer. Method: This is a nationwide , population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni-and multivariable estimations. Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n ¼ 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n ¼ 195) or other/multiple (n ¼ 187) distant metastases (p ¼ .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p ¼ .001) or other/multiple distant sites (HR 2.67, p ¼ .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p ¼ .245). Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.
Acta Oncologica
Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fa... more Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC). Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearson's correlation coefficient and Cohens kappa coefficient. Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearson's correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively. Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 11, 2016
Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and ... more Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator's choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% t...
Acta obstetricia et gynecologica Scandinavica, 1997
With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable d... more With current standard-dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first-line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60-80%. However, only 10-20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high-dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation. We report here our initial experiences of the use of high-dose chemotherapy supported by ASCT for patients with high-risk ovarian cancer. Two patients were treated at Uppsala University Hospital in 1992 and four patients at Turku University Central Hospital in 1994. The first four patients treated either after heavy previous chemotherapy or recurrent disease relapsed within 5-10 months. Two patients received high-dose therapy as part of first-line treatment. One of them had a relapse 18 mon...
International Journal of Gynecological Cancer, 1992
In a prospective study the immunohistochemically detectable tissue expression of the antigens CA-... more In a prospective study the immunohistochemically detectable tissue expression of the antigens CA-125 and CEA in 112 epithelial ovarian carcinomas and 23 borderline tumors was related to histologic features of the tumor and to patient survival. The CA-125 antigen was expressed mainly in non-mucinous tumors, with no evident association between histologic grade and immunoreactivity. CEA was expressed in mucinous tumors regardless of tumor grade. Flow cytometric DNA analysis was performed on fresh frozen tissue in a subgroup of 60 cases. There was no association between DNA ploidy or S-phase fraction and the CA-125 or CEA antigen expression. Tumor stage, size of residual tumor masses after surgery and DNA ploidy had independent associations with patient survival in multivariate log-rank analysis of prognostic factors. However, there was no association between the CA-125 or CEA antigen expression and patient survival. Thus, in ovarian carcinoma the expression of the CA-125 and CEA antigens seems to be independent of the inherent malignant potential of the tumor epithelium, while DNA analysis provides valuable prognostic information.
International Journal of Gynecological Cancer, 1992
The immunohistochemically detectable expression of CA-125 and CEA in ovarian tumor tissue from 18... more The immunohistochemically detectable expression of CA-125 and CEA in ovarian tumor tissue from 187 patients was related to corresponding preoperative serum levels. A strong positive association between tissue expression and the serum level of both the CA-125 and CEA antigens was found in cases of invasive epithelial ovarian carcinoma. However, this relationship was absent for CA-125 in borderline cases and patients with benign ovarian tumors, although the antigen frequently was detectable in them. The presence of ascites could be verified in 3 of 10 cases with benign CA-125 negative tumors, but elevated CA-125 levels in serum. &#39;False negative&#39; CA-125 levels were found in 6 borderline and 7 true invasive carcinoma cases despite positive tissue staining. Eight of those patients had limited stage I disease. The data suggests that although the tissue expression of the CA-125 and CEA antigens in invasive ovarian carcinoma has an important influence in the corresponding serum level, compartment barriers and low cell turnover in benign, and to a lesser extent borderline, cases result in low serum levels. In addition, other factors influence serum levels of CA-125, such as secondary peritoneal response with or without ascites, which may cause &#39;falsely elevated&#39; CA-125 results in benign disease.
Uploads
Papers by Bengt Tholander