Search

Your search keyword '"Heubner, M"' showing total 91 results
Start Over Author "Heubner, M"
91 results on '"Heubner, M"'

1. Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., Lin H., Colombo, N, Biagioli, E, Harano, K, Galli, F, Hudson, E, Antill, Y, Choi, C, Rabaglio, M, Marmé, F, Marth, C, Parma, G, Fariñas-Madrid, L, Nishio, S, Allan, K, Lee, Y, Piovano, E, Pardo, B, Nakagawa, S, Mcqueen, J, Zamagni, C, Manso, L, Takehara, K, Tasca, G, Ferrero, A, Tognon, G, Lissoni, A, Petrella, M, Laudani, M, Rulli, E, Uggeri, S, Barretina Ginesta, M, Zola, P, Casanova, C, Arcangeli, V, Antonuzzo, L, Gadducci, A, Cosio, S, Clamp, A, Persic, M, Mcneish, I, Tookman, L, Redondo Sanchez, A, Baldini, E, Palaia, I, Benedetti Panici, P, Takahashi, N, Lombard, J, Ardizzoia, A, Bologna, A, Herrero Ibáñez, A, Musolino, A, Márquez Vázquez, R, Pietzner, K, Braicu, E, Heinzelmann-Schwarz, V, Powell, M, Yokoyama, Y, Baron-Hay, S, Abeni, C, Martin Lorente, C, Cueva, J, Trillsch, F, Heitz, F, Ataseven, B, Petru, E, Heubner, M, Sadozye, A, Dubey, S, Tazbirkova, A, Tiley, S, Chrystal, K, Kim, S, Fehr, M, Scatchard, K, Anand, A, Taylor, A, Watary, H, Enomoto, T, Yoshihara, K, Selva-Nayagam, S, Karki, B, Harrison, M, Wilkinson, K, Goh, J, Glasgow, A, Chantrill, L, Lee, C, Bertolini, A, Narducci, F, Bellotti, G, Fusco, V, Aebi, S, Del Grande, M, Colombo, I, Tokunaga, H, Shigeta, S, Goss, G, Siow, Z, Steer, C, Lin, H, Colombo N., Biagioli E., Harano K., Galli F., Hudson E., Antill Y., Choi C. H., Rabaglio M., Marmé F., Marth C., Parma G., Fariñas-Madrid L., Nishio S., Allan K., Lee Y. C., Piovano E., Pardo B., Nakagawa S., McQueen J., Zamagni C., Manso L., Takehara K., Tasca G., Ferrero A., Tognon G., Lissoni A. A., Petrella M., Laudani M. E., Rulli E., Uggeri S., Barretina Ginesta M. P., Zola P., Casanova C., Arcangeli V., Antonuzzo L., Gadducci A., Cosio S., Clamp A., Persic M., McNeish I., Tookman L., Redondo Sanchez A., Baldini E., Palaia I., Benedetti Panici P., Takahashi N., Lombard J., Ardizzoia A., Bologna A., Herrero Ibáñez A. M., Musolino A., Márquez Vázquez R., Pietzner K., Braicu E., Heinzelmann-Schwarz V. A., Powell M., Yokoyama Y., Baron-Hay S., Abeni C., Martin Lorente C., Cueva J. F., Trillsch F., Heitz F., Ataseven B., Petru E., Heubner M. L., Sadozye A. H., Dubey S., Tazbirkova A., Tiley S., Chrystal K., Kim S. W., Fehr M., Scatchard K., Anand A., Taylor A., Watary H., Enomoto T., Yoshihara K., Selva-Nayagam S., Karki B., Harrison M., Wilkinson K., Goh J., Glasgow A., Chantrill L., Lee C., Bertolini A., Narducci F., Bellotti G., Fusco V., Aebi S., Del Grande M., Colombo I., Tokunaga H., Shigeta S., Goss G., Siow Z. R., Steer C., and Lin H.

Abstract

Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0–2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6–8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Findings: Between Oct 3, 2018, and Jan 7, 2022, 551 patients were r

Published
2024

4. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

Author

Lorusso, D, Hilpert, F, Gonzalez Martin, A, Rau, J, Ottevanger, P, Greimel, E, Luck, H, Selle, F, Colombo, N, Kroep, J, Mirza, M, Berger, R, Pardo, B, Grischke, E, Berton-Rigaud, D, Martinez-Garcia, J, Vergote, I, Redondo, A, Cardona, A, Bastiere-Truchot, L, Du Bois, A, Kurzeder, C, Del Campo, J, Bover, I, Barretina-Ginesta, P, Ortega, E, Garcia, Y, Romero, I, Poveda, A, Herrero, A, Vidal, L, Rubio, M, Romeo, M, Mendiola, C, Arranz, J, Santaballa, A, Gomez De Liano, A, Marme, F, Mahner, S, Canzler, U, Zorr, A, Gropp-Meier, M, Cayir, P, Schmalfeldt, B, Rautenberg, B, Meier, W, Belau, A, Gerber, B, Rein, D, Jackisch, C, Janni, W, Heubner, M, Pautier, P, Fabbro, M, Floquet, A, You, B, Favier, L, Joly, F, Weber, B, Hardy-Bessard, A, Gadducci, A, Tognon, G, Decensi, A, Savarese, A, Pisano, C, Sonke, G, Reyners, A, Kristensen, G, Bjurberg, M, Rosenberg, P, Marth, C, Lorusso D., Hilpert F., Gonzalez Martin A., Rau J., Ottevanger P., Greimel E., Luck H. -J., Selle F., Colombo N., Kroep J. R., Mirza M. R., Berger R., Pardo B., Grischke E. -M., Berton-Rigaud D., Martinez-Garcia J., Vergote I., Redondo A., Cardona A., Bastiere-Truchot L., Du Bois A., Kurzeder C., Del Campo J. M., Bover I., Barretina-Ginesta P., Ortega E., Garcia Y., Romero I., Poveda A., Herrero A., Vidal L., Rubio M. J., Romeo M., Mendiola C., Arranz J. A., Santaballa A., Gomez De Liano A., Marme F., Mahner S., Canzler U., Zorr A., Gropp-Meier M., Cayir P., Schmalfeldt B., Rautenberg B., Meier W., Belau A., Gerber B., Rein D., Jackisch C., Janni W., Heubner M., Pautier P., Fabbro M., Floquet A., You B., Favier L., Joly F., Weber B., Hardy-Bessard A. -C., Gadducci A., Tognon G., DeCensi A., Savarese A., PISANO, CARLO MARIA, Sonke G., Reyners A., Kristensen G., Bjurberg M., Rosenberg P., Marth C., Lorusso, D, Hilpert, F, Gonzalez Martin, A, Rau, J, Ottevanger, P, Greimel, E, Luck, H, Selle, F, Colombo, N, Kroep, J, Mirza, M, Berger, R, Pardo, B, Grischke, E, Berton-Rigaud, D, Martinez-Garcia, J, Vergote, I, Redondo, A, Cardona, A, Bastiere-Truchot, L, Du Bois, A, Kurzeder, C, Del Campo, J, Bover, I, Barretina-Ginesta, P, Ortega, E, Garcia, Y, Romero, I, Poveda, A, Herrero, A, Vidal, L, Rubio, M, Romeo, M, Mendiola, C, Arranz, J, Santaballa, A, Gomez De Liano, A, Marme, F, Mahner, S, Canzler, U, Zorr, A, Gropp-Meier, M, Cayir, P, Schmalfeldt, B, Rautenberg, B, Meier, W, Belau, A, Gerber, B, Rein, D, Jackisch, C, Janni, W, Heubner, M, Pautier, P, Fabbro, M, Floquet, A, You, B, Favier, L, Joly, F, Weber, B, Hardy-Bessard, A, Gadducci, A, Tognon, G, Decensi, A, Savarese, A, Pisano, C, Sonke, G, Reyners, A, Kristensen, G, Bjurberg, M, Rosenberg, P, Marth, C, Lorusso D., Hilpert F., Gonzalez Martin A., Rau J., Ottevanger P., Greimel E., Luck H. -J., Selle F., Colombo N., Kroep J. R., Mirza M. R., Berger R., Pardo B., Grischke E. -M., Berton-Rigaud D., Martinez-Garcia J., Vergote I., Redondo A., Cardona A., Bastiere-Truchot L., Du Bois A., Kurzeder C., Del Campo J. M., Bover I., Barretina-Ginesta P., Ortega E., Garcia Y., Romero I., Poveda A., Herrero A., Vidal L., Rubio M. J., Romeo M., Mendiola C., Arranz J. A., Santaballa A., Gomez De Liano A., Marme F., Mahner S., Canzler U., Zorr A., Gropp-Meier M., Cayir P., Schmalfeldt B., Rautenberg B., Meier W., Belau A., Gerber B., Rein D., Jackisch C., Janni W., Heubner M., Pautier P., Fabbro M., Floquet A., You B., Favier L., Joly F., Weber B., Hardy-Bessard A. -C., Gadducci A., Tognon G., DeCensi A., Savarese A., PISANO, CARLO MARIA, Sonke G., Reyners A., Kristensen G., Bjurberg M., Rosenberg P., and Marth C.

Abstract

Introduction The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes. Patients and methods Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression. Results At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms. Discussion Consistent with

Published
2019

7. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

Author

Lorusso, D., Hilpert, F., Martin, A.G., Rau, J., Ottevanger, P., Greimel, E., Luck, H.J., Selle, F., Colombo, N., Kroep, J.R., Mirza, M.R., Berger, R., Pardo, B., Grischke, E.M., Berton-Rigaud, D., Martinez-Garcia, J., Vergote, I., Redondo, A., Cardona, A., Bastiere-Truchot, L., Bois, A. du, Kurzeder, C., Campo, J.M. del, Bover, I., Barretina-Ginesta, P., Ortega, E., Garcia, Y., Romero, I., Poveda, A., Herrero, A., Vidal, L., Rubio, M.J., Romeo, M., Mendiola, C., Arranz, J.A., Santaballa, A., Liano, A.G. de, Marme, F., Mahner, S., Canzler, U., Zorr, A., Gropp-Meier, M., Cayir, P., Schmalfeldt, B., Rautenberg, B., Meier, W., Belau, A., Gerber, B., Rein, D., Jackisch, C., Janni, W., Heubner, M., Pautier, P., Fabbro, M., Floquet, A., You, B., Favier, L., Joly, F., Weber, B., Hardy-Bessard, A.C., Gadducci, A., Tognon, G., DeCensi, A., Savarese, A., Pisano, C., Sonke, G., Reyners, A., Kristensen, G., Bjurberg, M., Rosenberg, P., Marth, C., PENELOPE Trial Investigators, Lorusso, D, Hilpert, F, Gonzalez Martin, A, Rau, J, Ottevanger, P, Greimel, E, Luck, H, Selle, F, Colombo, N, Kroep, J, Mirza, M, Berger, R, Pardo, B, Grischke, E, Berton-Rigaud, D, Martinez-Garcia, J, Vergote, I, Redondo, A, Cardona, A, Bastiere-Truchot, L, Du Bois, A, Kurzeder, C, Del Campo, J, Bover, I, Barretina-Ginesta, P, Ortega, E, Garcia, Y, Romero, I, Poveda, A, Herrero, A, Vidal, L, Rubio, M, Romeo, M, Mendiola, C, Arranz, J, Santaballa, A, Gomez De Liano, A, Marme, F, Mahner, S, Canzler, U, Zorr, A, Gropp-Meier, M, Cayir, P, Schmalfeldt, B, Rautenberg, B, Meier, W, Belau, A, Gerber, B, Rein, D, Jackisch, C, Janni, W, Heubner, M, Pautier, P, Fabbro, M, Floquet, A, You, B, Favier, L, Joly, F, Weber, B, Hardy-Bessard, A, Gadducci, A, Tognon, G, Decensi, A, Savarese, A, Pisano, C, Sonke, G, Reyners, A, Kristensen, G, Bjurberg, M, Rosenberg, P, Marth, C, Targeted Gynaecologic Oncology (TARGON), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Oncology, Receptor, ErbB-3, medicine.medical_treatment, Carcinoma, Ovarian Epithelial, Deoxycytidine, 0302 clinical medicine, Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, Aged, 80 and over, Ovarian Neoplasms, 0303 health sciences, education.field_of_study, Obstetrics and Gynecology, Middle Aged, Progression-Free Survival, ovarian cancer, patient-reported outcomes, 030220 oncology & carcinogenesis, Female, Pertuzumab, medicine.drug, Adult, medicine.medical_specialty, Paclitaxel, overall survival, Population, Placebo, patient-reported outcome, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Double-Blind Method, HER3, pertuzumab, Internal medicine, medicine, Humans, Patient Reported Outcome Measures, RNA, Messenger, education, 030304 developmental biology, Aged, Chemotherapy, business.industry, medicine.disease, Gemcitabine, Drug Resistance, Neoplasm, Topotecan, business, Ovarian cancer
Abstract

IntroductionThe PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes.Patients and methodsEligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression.ResultsAt database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms.DiscussionConsistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes.ClinicalTrials.gov:ClinicalTrials.gov:NCT01684878.

Published
2019

9. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial

Author

du Bois, A, Kristensen, G, Ray-Coquard, I, Reuss, A, Pignata, S, Colombo, N, Denison, U, Vergote, I, Del Campo JM, Ottevanger, P, Heubner, M, Minarik, T, Sevin, E, de Gregorio, N, Bidziński, M, Pfisterer, J, Malander, S, Hilpert, F, Mirza, Mr, Scambia, G, Meier, W, Nicoletto, Mo, Bjørge, L, Lortholary, A, Sailer, Mo, Merger, M, Harter, P, AGO Study Group led Gynecologic Cancer Intergroup/European Network of Gynaecologic Oncology Trials Groups Intergroup Consortium: Università degli Studi di Torino ITA, Ferrero, A, Et, Al, du Bois, A, Kristensen, G, Ray Coquard, I, Reuss, A, Pignata, S, Colombo, N, Denison, U, Vergote, I, Del Campo, J, Ottevanger, P, Heubner, M, Minarik, T, Sevin, E, de Gregorio, N, Bidziński, M, Pfisterer, J, Malander, S, Hilpert, F, Mirza, M, Scambia, G, Meier, W, Nicoletto, M, Bjørge, L, Lortholary, A, Sailer, M, Merger, M, and Harter, P

Subjects
0301 basic medicine, Indoles, Clinical Trial, Phase III, Medizin, ovarian cancer nintedanib angiogenesis inhibitor chemotherapy ENGOT clinical trial, Gastroenterology, Carboplatin, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Medicine, Peritoneal Neoplasms, Aged, 80 and over, Ovarian Neoplasms, education.field_of_study, Medicine (all), Research Support, Non-U.S. Gov't, Anemia, Cytoreduction Surgical Procedures, Middle Aged, Intention to Treat Analysis, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multicenter Study, Oncology, Tolerability, 030220 oncology & carcinogenesis, Randomized Controlled Trial, Disease Progression, Female, Nintedanib, medicine.drug, Adult, Diarrhea, medicine.medical_specialty, Neutropenia, Paclitaxel, Bevacizumab, Population, Placebo, Disease-Free Survival, Young Adult, 03 medical and health sciences, Double-Blind Method, Internal medicine, Journal Article, Fallopian Tube Neoplasms, Humans, Progression-free survival, education, Response Evaluation Criteria in Solid Tumors, Aged, Neoplasm Staging, business.industry, Carcinoma, medicine.disease, Thrombocytopenia, Surgery, Settore MED/40 - GINECOLOGIA E OSTETRICIA, 030104 developmental biology, chemistry, business, Febrile neutropenia
Abstract

BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer.METHODS: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min) and paclitaxel (175 mg/m(2)) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01015118.FINDINGS: Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in 22 countries: 911 to the nintedanib group and 455 to the placebo group. 486 (53%) of 911 patients in the nintedanib group experienced disease progression or death compared with 266 (58%) of 455 in the placebo group. Median progression-free survival was significantly longer in the nintedanib group than in the placebo group (17·2 months [95% CI 16·6-19·9] vs 16·6 months [13·9-19·1]; hazard ratio 0·84 [95% CI 0·72-0·98]; p=0·024). The most common adverse events were gastrointestinal (diarrhoea: nintedanib group 191 [21%] of 902 grade 3 and three [INTERPRETATION: Nintedanib in combination with carboplatin and paclitaxel is an active first-line treatment that significantly increases progression-free survival for women with advanced ovarian cancer, but is associated with more gastrointestinal adverse events. Future studies should focus on improving patient selection and optimisation of tolerability.FUNDING: Boehringer Ingelheim.

Published
2016

10. Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial

Author

Vergote, I. Scambia, G. O'Malley, D.M. Van Calster, B. Park, S.-Y. del Campo, J.M. Meier, W. Bamias, A. Colombo, N. Wenham, R.M. Covens, A. Marth, C. Raza Mirza, M. Kroep, J.R. Ma, H. Pickett, C.A. Monk, B.J. Park, S.Y. Song, Y.S. Makarova, Y. Trinidad, J. Ngan, H.Y.S. Aravantinos, G. Nam, J.-H. Gorbunova, V. Krikunova, L. Bae, D.-S. Arija, J.A.A. Mirza, M.R. Zamagni, C. Papandreou, C. Raspagliesi, F. Lisyanskaya, A. Benzaquen, A.O. Tognon, G. Ortega, E. Herraez, A.C. Buscema, J. Green, A. Burger, R. Sakaeva, D. Sanchez, A.R. Ghamande, S. King, L. Petru, E. Peen, U. Takeuchi, S. Ushijima, K. Martin, A.G. Kamelle, S. Carney, M. Forget, F. Bentley, J. Sehouli, J. Zola, P. Kato, H. Fadeeva, N. Gotovkin, E. Vladimirov, V. Marin, M.R. Alia, E.G. Shahin, M. Bhoola, S. Tewari, K. Anderson, D. Honhon, B. Pelgrims, J.G. Oza, A. Jimenez, J.G.-D. Hansen, V. Benjamin, I. Renard, V. Van den Bulck, H. Haenle, C. Koumakis, G. Yokota, H. Popov, V. Bradley, W. Wenham, R. Reid, R. McNamara, D. Friedman, R. Barlin, J. Spirtos, N. Chapman, J. Sevelda, P. Huizing, M. Lamot, C. Goffin, F. Hondt, L.D. Covens, A. Spadafora, S. Rautenberg, B. Reimer, T. Möbus, V. Hilpert, F. Gropp-Meier, M. Savarese, A. Pignata, S. Verderame, F. Mizuno, M. Takano, H. Ottevanger, P. Velasco, A.P. Palacio-Vazquez, I. Law, A. McIntyre, K. Teneriello, M. Fields, A. Lentz, S. Street, D. Schwartz, B. Mannel, R. Lim, P. Pulaski, H. Janni, W. Zorr, A. Karck, U. Cheng, A.C.K. Sorio, R. Gridelli, C. Aoki, D. Oishi, T. Hirashima, Y. Boere, I. Ferrer, E.F. Braly, P. Wilks, S. Lee, C. Schilder, J. Veljovich, D. Secord, A. Davis, K. Rojas-Espaillat, L. Lele, S. DePasquale, S. Squatrito, R. Schauer, C. Dirix, L. Vuylsteke, P. Joosens, E. Provencher, D. Lueck, H.-J. Hein, A. Burges, A. Canzler, U. Park-Simon, T.-W. Griesinger, F. Gadducci, A. Alabiso, O. Okamoto, A. Sawasaki, T. Saito, T. Ibañez, A.H. Calomeni, C. Spillman, M. Choksi, J. Taylor, N. Muller, C. Moore, D. DiSilvestro, P. Cunningham, M. Rose, P. Oppelt, P. Verhoeven, D. Graas, M.-P. Ghatage, P. Tonkin, K. Kurzeder, C. Schnappauf, B. Müller, V. Schmalzrie, H. Kalofonos, H. Bruzzone, M. Kroep, J. Diaz, C.C. Garcia, J.M. Polo, S.H. Garrison, M. Rocconi, R. Andrews, S. Bristow, R. McHale, M. Basil, J. Houck III, W. Bell, M. Cosin, J. Modesitt, S. Kendrick, J. Wade III, J. Wong, C. Evans, A. Buekers, T. Vanderkwaak, T. Ferriss, J. Darus, C. DAndre, S. Higgins, R. Monk, B. Bakkum-Gamez, J. DeMars, L. Van Le, L. Puls, L. Trehan, S. LaPolla, J. Michelson, E.D. Merchant, J. Peterson, C. Reid, G. Seago, D. Zweizig, S. Gajewski, W. Panwalkar, A. Leikermoser, R. Bogner, G. Debruyne, P. D'hondt, R. Berteloot, P. Kerger, J. Biagi, J. Castonguay, V. Welch, S. Muhic, A. Heubner, M. Grischke, E.-M. Rack, B. Fleisch, M. Lordick, F. Pectasides, D. Ho, W.M. Selvaggi, L. Vasquez, F.M. Villanueva, W.O.B. Alavez, A.M. Kessels, L. Bertran, A.S. Fernandez, C.M. Fabregat, M.B. Del Prete, S. Elkas, J. Cecchi, G. Kumar, P. Huh, W. Messing, M. Karimi, M. Kelley, A. Edraki, B. Mutch, D. Leiserowitz, G. Anderson, J. Lentz, S. Chambers, S. Morris, R. Waggoner, S. Gordon, A. Method, M. Johnson, P. Lord, R. Drake, J. Sivarajan, K. Midathada, M. Rice, K. Wadsworth, T. Pavelka, J. Edwards, R. Miller, D.S. Ford, P.L. Hurteau, J. Bender, D. Schimp, V. Creasman, W. Lerner, R. Chamberlain, D. Kueck, A. McDonald, J. Malad, S. Robinson-Bennett, B. Davidson, S. Krivak, T. Lestingi, T. Arango, H. Berard, P. Finkelstein, K. Gaur, R. Krasner, C. Ueland, F. Talmage, L. Yamada, S. Sutton, G. Potkul, R. Prasad-Hayes, M. Osborne, J. Celano, P. Thigpen, J. Sharma, S. Schilder, R. Tammela, J. Kemeny, M. Brown, A. Eisenhauer, E. Williams, J. Rowland, K. Nahum, K. Burke, J. Dar, Z. Fleming, N. Gibb, R. Guirguis, A. Herzog, T. John, V. Kumar, S. Kamat, A. Kassar, M. Leitao, M. Levine, L. Mendez, L. Patel, D. Berry, E. Warshal, D. Wolf, J. Zarwan, C. Collins, Y. Spitzer, G. Miller, B. Einstein, M. TRINOVA-3/ENGOT-ov2/GOG-3001 investigators

Abstract

Background: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. Methods: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres)in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO)stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1)using a permuted block method (block size of six patients)to receive six cycles of paclitaxel (175 mg/m2)and carboplatin (area under the serum concentration-time curve 5 or 6)every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. Findings: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7–34·2), 626 patients had progression-free survival events (405 [60%]of 678 in the trebananib group and 221 [66%]of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0–17·6])and the placebo group (15·0 months [12·6–16·1])groups (hazard ratio 0·93 [95% CI 0·79–1·09]; p=0·36). 512 (76%)of 675 patients in the trebananib group and 237 (71%)of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%]vs placebo 126 [38%])anaemia (76 [11%]vs 40 [12%]), and leucopenia (81 [12%]vs 35 [10%]). 269 (40%)patients in the trebananib group and 104 (31%)in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. Interpretation: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. Funding: Amgen. © 2019 Elsevier Ltd

Published
2019

11. P193 p53 and p16 expression profiles identify three prognostically subgroups in vulvar cancer: a TMA based study by the AGO-CaRE-translational study group

Author

Wölber, L, primary, Prieske, K, additional, Eulenburg, C, additional, de Gregorio, N, additional, Klapdor, R, additional, Kalder, M, additional, Braicu, I, additional, Fuerst, S, additional, Klar, M, additional, Strauss, H-G, additional, Mehlhorn, G, additional, Meier, W, additional, Ignatov, A, additional, Mustea, A, additional, Jueckstock, J, additional, Schmidt, G, additional, Bauerschlag, D, additional, Hellriegel, M, additional, Canzler, U, additional, Luyten, A, additional, Kommoss, S, additional, Hantschmann, P, additional, Heubner, M, additional, Mahner, S, additional, Burandt, E, additional, and Study Group, AGO, additional

Published
2019
Full Text
View/download PDF

12. Prevalence of somatic mutations in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1 study)

Author

Hauke, J., Hahnen, E., Burges, A., Reuss, A., Gregorio, N. D., El-Balat, A., Richters, L., Hilpert, F., Schmidt, S., Meier, W., Gevensleben, H., Heubner, M., Dietrich, D., Kast, K., Braicu, E., Neunhoeffer, T., Schmutzler, R. K., Harter, P., Hauke, J., Hahnen, E., Burges, A., Reuss, A., Gregorio, N. D., El-Balat, A., Richters, L., Hilpert, F., Schmidt, S., Meier, W., Gevensleben, H., Heubner, M., Dietrich, D., Kast, K., Braicu, E., Neunhoeffer, T., Schmutzler, R. K., and Harter, P.

Published
2018

14. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12): a randomised, double-blind, placebo-controlled phase 3 trial

Author

Bois, A. du, Kristensen, G., Ray-Coquard, I., Reuss, A., Pignata, S., Colombo, N., Denison, U., Vergote, I., Campo, J.M. Del, Ottevanger, P.B., Heubner, M., Minarik, T., Sevin, E., Gregorio, N. de, Bidzinski, M., Pfisterer, J., Malander, S., Hilpert, F., Mirza, M.R., Scambia, G., Meier, W., Nicoletto, M.O., Bjorge, L., Lortholary, A., Sailer, M.O., Merger, M., Harter, P., Bois, A. du, Kristensen, G., Ray-Coquard, I., Reuss, A., Pignata, S., Colombo, N., Denison, U., Vergote, I., Campo, J.M. Del, Ottevanger, P.B., Heubner, M., Minarik, T., Sevin, E., Gregorio, N. de, Bidzinski, M., Pfisterer, J., Malander, S., Hilpert, F., Mirza, M.R., Scambia, G., Meier, W., Nicoletto, M.O., Bjorge, L., Lortholary, A., Sailer, M.O., Merger, M., and Harter, P.

Abstract

Item does not contain fulltext, BACKGROUND: Angiogenesis is a target in the treatment of ovarian cancer. Nintedanib, an oral triple angiokinase inhibitor of VEGF receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, has shown activity in phase 2 trials in this setting. We investigated the combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. METHODS: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB-IV ovarian cancer and upfront debulking surgery were stratified by postoperative resection status, FIGO stage, and planned carboplatin dose. Patients were randomly assigned (2:1) via an interactive voice or web-based response system to receive six cycles of carboplatin (AUC 5 mg/mL per min or 6 mg/mL per min) and paclitaxel (175 mg/m(2)) in addition to either 200 mg of nintedanib (nintedanib group) or placebo (placebo group) twice daily on days 2-21 of every 3-week cycle for up to 120 weeks. Patients, investigators, and independent radiological reviewers were masked to treatment allocation. The primary endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01015118. FINDINGS: Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in 22 countries: 911 to the nintedanib group and 455 to the placebo group. 486 (53%) of 911 patients in the nintedanib group experienced disease progression or death compared with 266 (58%) of 455 in the placebo group. Median progression-free survival was significantly longer in the nintedanib group than in the placebo group (17.2 months [95% CI 16.6-19.9] vs 16.6 months [13.9-19.1]; hazard ratio 0.84 [95% CI 0.72-0.98]; p=0.024). The most common adverse events were gastrointestina

Published
2016

15. Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarian cancer (OC) patients (AGO TR-1)

Author

Marme, F., Harter, P., Hauke, J., Heitz, F., Reuss, A., Kommoss, S., Heimbach, A., Prieske, K., Richters, L., Burges, A., Neidhardt, G., de Gregorio, N., El-Balat, A., Hilpert, F., Meier, W., Heubner, M., Kast, K., Braicu, I., Hahnen, E., Schmutzler, R., Marme, F., Harter, P., Hauke, J., Heitz, F., Reuss, A., Kommoss, S., Heimbach, A., Prieske, K., Richters, L., Burges, A., Neidhardt, G., de Gregorio, N., El-Balat, A., Hilpert, F., Meier, W., Heubner, M., Kast, K., Braicu, I., Hahnen, E., and Schmutzler, R.

Published
2016

16. Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarian cancer (OC) patients (AGO TR-1)

Author

Kommoss, S, primary, Harter, P, additional, Hauke, J, additional, Heitz, F, additional, Reuss, A, additional, Marmé, F, additional, Heimbach, A, additional, Prieske, K, additional, Richters, L, additional, Burges, A, additional, Neidhardt, G, additional, de Gregorio, N, additional, El-Balat, A, additional, Hilpert, F, additional, Meier, W, additional, Heubner, M, additional, Kast, K, additional, Braicu, I, additional, Hahnen, E, additional, and Schmutzler, R, additional

Published
2016
Full Text
View/download PDF

19. Temsirolimus in women with platinum-resistant ovarian cancer or advanced/recurrent endometrial cancer: a multicenter phase II trial of the AGO Study Group (AGO-GYN 8)

Author

Hilpert, F, primary, Kurzeder, C, additional, Schmalfeldt, B, additional, Neuser, P, additional, de Gregorio, N, additional, Pfisterer, J, additional, Park-Simon, TW, additional, Mahner, S, additional, Schröder, W, additional, Lück, HJ, additional, Heubner, M, additional, Hanker, L, additional, Thiel, F, additional, and Emons, G, additional

Published
2014
Full Text
View/download PDF

36. p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group.

Author

Woelber L, Prieske K, Eulenburg C, Oliveira-Ferrer L, de Gregorio N, Klapdor R, Kalder M, Braicu I, Fuerst S, Klar M, Strauss HG, Beckmann M, Meier W, Ignatov A, Mustea A, Jueckstock J, Schmidt G, Bauerschlag D, Hellriegel M, Canzler U, Petry KU, Kommoss S, Hantschmann P, Heubner M, Mahner S, and Burandt E

Subjects
Adult, Aged, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell virology, Female, Follow-Up Studies, Germany epidemiology, Humans, Immunohistochemistry, Middle Aged, Mutation, Papillomavirus Infections complications, Papillomavirus Infections diagnosis, Papillomavirus Infections virology, Phenotype, Prognosis, Retrospective Studies, Survival Analysis, Tissue Array Analysis, Translational Research, Biomedical, Tumor Suppressor Protein p53 genetics, Up-Regulation, Vulvar Neoplasms diagnosis, Vulvar Neoplasms mortality, Vulvar Neoplasms virology, Biomarkers, Tumor metabolism, Carcinoma, Squamous Cell metabolism, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Tumor Suppressor Protein p53 metabolism, Vulvar Neoplasms metabolism
Abstract

Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed., Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance., Study Design: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction., Results: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53- (n=132), and p16-/p53- (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53- tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16-/p53- tumors; P<.0001) and showed lower rates of lymph-node involvement (28.0% vs 42.3% for p53+, respectively, 30.2% for p16-/p53- tumors; P=.050). Notably, 2-year-disease-free and overall survival rates were significantly different among the groups: disease-free survival, 47.1% (p53+), 60.2% (p16-/p53-), and 63.9% (p16+/p53-) (P<.001); overall survival, 70.4% (p53+), 75.4% (p16-/p53-), and 82.5% (p16+/p53-) (P=.002). In multivariate analysis, the p16+/p53- phenotype showed a consistently improved prognosis compared with the other groups (hazard ratio, 0.66; 95% confidence interval, 0.44-0.99; P=.042)., Conclusion: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
Full Text
View/download PDF

37. Suspensory Ligaments of the Female Genital Organs: MRI Evaluation with Intraoperative Correlation.

Author

Kaniewska M, Gołofit P, Heubner M, Maake C, and Kubik-Huch RA

Subjects
Female, Humans, Genital Diseases, Female diagnostic imaging, Genital Diseases, Female pathology, Genitalia, Female anatomy & histology, Genitalia, Female diagnostic imaging, Ligaments anatomy & histology, Ligaments diagnostic imaging, Magnetic Resonance Imaging
Abstract

The uterus, which plays an important role in the reproductive process, provides a home for the developing fetus and so must be in a stable, though flexible, location. Various structures with suspensory ligaments help provide this berth. MRI with high spatial resolution allows us to detect and evaluate these relatively fine structures. Under physiologic conditions, MRI can be used to depict uterine and ovarian ligaments (ie, the uterosacral, cardinal, and round ligaments, as well as the suspensory ligament of the ovary). In the presence of pathologic conditions (inflammation, endometriosis, tumors), the suspensory ligaments may appear thickened or invaded, which makes their delineation easier. Understanding the normal anatomy of the suspensory ligaments of the female genital organs and using a standardized nomenclature are essential for identifying and reporting related pathologic conditions. The female pelvic anatomy and the suspensory ligaments of the female genital organs are described as depicted with MRI. Also, the compartmental anatomy of the female pelvis is explained, including the extraperitoneal pelvic spaces. Finally, a checklist is provided for structured reporting of the MRI findings in the female pelvis. Online supplemental material is available for this article. © RSNA, 2018.

Published
2018
Full Text
View/download PDF

38. Evaluation of a novel ELISA for the tumor-associated antigen CA 72-4 in patients with ovarian cancer.

Author

Buderath P, Kasimir-Bauer S, Aktas B, Rasch J, Kimmig R, Zeller T, and Heubner M

Abstract

Aim: Cancer antigen 72-4 (CA 72-4) is an established tumor marker in ovarian cancer. We evaluated a new solid-phase ELISA (DRG TM-CA 72-4 ELISA)., Materials & Methods: Repeated measures of test samples and controls were performed to evaluate reliability and reproducibility. Afterward, we performed analyses on the sera of 150 patients with primarily diagnosed ovarian cancer. Results were compared with those of the Cobas CA 72-4 kit. Results were correlated with clinical patient data., Results: Results of the DRG TM-CA 72-4 ELISA were reproducible with acceptable deviations within measures, and the measured CA 72-4 serum concentrations were well in accordance with the references. High concentrations were significantly associated with grading, tumor stage and tumor residuals after surgery., Competing Interests: Financial & competing interests disclosure T Zeller is employed at DRG Instruments GmbH. The TM-CA 72–4 ELISA Assay was provided by DRG Instruments GmbH at no cost. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Published
2016
Full Text
View/download PDF

39. Embryologically based radical hysterectomy as peritoneal mesometrial resection (PMMR) with pelvic and para-aortic lymphadenectomy for loco-regional tumor control in endometrial cancer: first evidence for efficacy.

Author

Kimmig R, Iannaccone A, Aktas B, Buderath P, and Heubner M

Subjects
Adult, Brachytherapy, Carcinoma pathology, Endometrial Neoplasms pathology, Female, Humans, Laparoscopy, Mesoderm pathology, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Pelvis pathology, Peritoneal Neoplasms pathology, Peritoneal Neoplasms surgery, Peritoneum pathology, Radiotherapy, Adjuvant, Uterine Neoplasms pathology, Uterine Neoplasms surgery, Vagina pathology, Endometrial Neoplasms surgery, Hysterectomy, Lymph Node Excision methods, Mesoderm surgery, Peritoneum surgery
Abstract

Objective: To evaluate the feasibility and efficacy of embryologically based compartmental surgery for locoregional tumor control in intermediate and high risk endometrial cancer: peritoneal mesometrial resection with therapeutic pelvic and para-aortic lymphadenectomy by robotically assisted laparoscopy., Methods: 75 consecutive surgically treated patients with uterine malignancies have been analyzed. 68 patients with histologically proven endometrial cancer and complete robotically assisted surgery have been included in this study on morbidity and oncological outcome. 56 % of the patients were at intermediate/high risk with either stage IAG3 or IB (n = 22) or stage II-IV (n = 16). Adjuvant EBRT was offered to three patients only (4 %), whereas five received isolated vaginal brachytherapy (7 %). Indocyanine-green (ICG) fluorescence lymphography is demonstrated being useful for additional intraoperative visualization of the compartment borders and lymphatic drainage to the postponed lymph compartments., Results: After a mean follow-up of 32 months, there were only two loco-regional recurrences (2.9 %). Both recurrences were apparently cured by salvage therapy. 9 patients died; 6 (8.8 %) from metastatic disease (5) or unknown cause (1), 3 (4.4 %) from intercurrent disease without evidence of disease. One patient (1.4 %) experienced a peritoneal carcinosis and is alive. There were 8/68 perioperative complications (12 %). No perioperative mortality was observed., Conclusions: Embryologically defined compartmental surgery by robotically assisted laparoscopy seems to be feasible and safe in endometrial cancer. The low loco-regional recurrence rate of 2.9 % in spite of a very low percentage of adjuvant radiotherapy and 56 % of intermediate/high risk tumors should stimulate to initiate a multicentre trial to evaluate the value of compartmental surgery for prevention of locoregional recurrence in endometrial cancer.

Published
2016
Full Text
View/download PDF

40. B3-lesions of the breast and cancer risk - an analysis of mammography screening patients.

Author

Hoffmann O, Stamatis GA, Bittner AK, Arnold G, Schnabel R, Krüger K, Kimmig R, and Heubner M

Abstract

The use of mammography screening, followed by needle core biopsy (NCB), is associated with an increasing amount of invasive procedures. A considerable amount of specimens must be classified as lesions with uncertain malignant potential (B3-lesion). In these cases, an open biopsy is indicated for further diagnosis. We evaluated patients with B3-lesions to determine the risk of malignancy corresponding to the histopathological NCB results and the type of radiological lesion identified. A total of 95 patients participating in the German mammography screening program with a B3-lesion following NCB (104 B3-lesions in total) were included in our analysis. We analyzed the correlation between the initial histopathological findings from the NCB specimen and cancer risk. We further analyzed the correlations of malignant results with the type of mammographic lesion. In 23 cases (22%), histopathological examination following excision revealed a malignant lesion, including invasive and in situ carcinoma. The positive predictive value of the subgroups of B3-lesions ranged between 0.11 and 0.31; the B3-lesion associated with the highest cancer risk was the atypical ductal hyperplasia; however, no significant difference was observed between the B3-lesion subgroups (P=0.309) regarding the risk of malignancy. Comparing the different types of mammographic findings, such as radiological mass or microcalcifications, there was no significant difference in the risk for malignancy (P=0.379). The different types of B3-lesions did not exhibit differences in the risk for malignancy, and the morphological type of mammographic lesion does not appear to be correlated with cancer risk; therefore, our results underline the need for open biopsy in patients with B3-lesions following NCB.

Published
2016
Full Text
View/download PDF

41. Intraoperative navigation in robotically assisted compartmental surgery of uterine cancer by visualisation of embryologically derived lymphatic networks with indocyanine-green (ICG).

Author

Kimmig R, Aktas B, Buderath P, Rusch P, and Heubner M

Subjects
Adult, Feasibility Studies, Female, Humans, Hysterectomy, Intraoperative Care, Laparoscopy, Lymph Node Excision, Middle Aged, Uterine Neoplasms diagnostic imaging, Coloring Agents, Indocyanine Green, Lymphatic Vessels diagnostic imaging, Optical Imaging, Robotic Surgical Procedures, Uterine Neoplasms surgery
Abstract

Background and Objectives: To evaluate feasibility of intraoperative visualization of embryologically defined organ compartments and their drainage by ICG in uterine cancer., Methods: Total of 2.5 mg of ICG have been injected into cervix or corpus in uterine cancer patients immediately prior to surgery. Green fluorescence was intermittently detected during robotically assisted laparoscopic surgery (Firefly System®, Intuitve Surgical Inc.). Total of 36 patients with uterine cancer without macroscopically suspicious nodes were evaluated with respect to their compartmental lymphatic network, collecting lymphatic vessels, and the connection to the postponed lymph basins., Results: Müllerian (sub) compartment and transport of lymph fluid along the lymphatic collectors and connecting vessels to the postponed lymph basins could be visualized invariably in all patients. Cervix drained along the ligamentous and caudal part of vascular mesometria, whereas midcorporal and fundal drainage occurred along the upper part of vascular mesometria and along the mesonephric pathway along the ovarian vessels., Conclusions: Visualization of lymphatic network and downstream flow of lymphatic fluid to the postponed lymph basins by ICG is feasible; it can be used to navigate along compartment boarders for education, intraoperative orientation, and quality control. It seems to confirm the compartmental order of pelvic organ systems and postponed lymph basins. J. Surg. Oncol. 2016;113:554-559. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Published
2016
Full Text
View/download PDF

42. Robotically assisted peritoneal mesometrial resection (PMMR) in endometrial cancer supported by ICG labeling of the compartmental lymphatic system.

Author

Kimmig R, Aktas B, Buderath P, and Heubner M

Abstract

•Peritoneal mesometrial resection is a compartment based radical hysterectomy in endometrial cancer•ICG staining of the lymph-vessel system facilitates identification of compartment borders•Fluorescence based HD-video documentation supports education in surgery of endometrial cancer.

Published
2016
Full Text
View/download PDF

43. Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects.

Author

Heubner M, Wimberger P, Kasimir-Bauer S, Singer BB, Ruf P, Kimmig R, and Siffert W

Subjects
Adult, Aged, Case-Control Studies, Cell Adhesion Molecules metabolism, Cell Adhesion Molecules therapeutic use, Epithelial Cell Adhesion Molecule, Female, Genotype, HEK293 Cells, Humans, Middle Aged, Neoplasm Staging, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Risk, Transfection, Antibodies, Bispecific genetics, Antigens, Neoplasm genetics, Cell Adhesion Molecules genetics, Ovarian Neoplasms genetics
Abstract

Purpose: EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab., Methods: DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T>C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3-the EpCAM binding site of catumaxomab-to determine antibody binding., Results: One SNP was detected in exon 3 (4461T>C; rs1126497), resulting in an amino acid exchange at position 115 (Met115Thr). Another polymorphism was found in the 3'UTR (17225A>G; rs1421). Genotyping of patients and controls for these SNPs did not reveal significant differences in genotype distribution. Regarding 17225A>G, the homozygous AA-genotype was associated with diminished progression-free survival (PFS; p = 0.032). Overall survival, FIGO-stage, grading, and age did not differ significantly between genotypes. FACS analysis of transfected Hek293 cells overexpressing EpCAM 115Met/Thr showed binding of HO-3 to both proteins., Conclusions: The AA-genotype of 17225A>G seems to be associated with diminished PFS in ovarian cancer patients. The amino acid exchange resulting from 4461T>C does not appear to alter binding of HO-3, suggesting that treatment with catumaxomab can be offered to patients regardless of their TACSTD1-genotype.

Published
2015
Full Text
View/download PDF

44. Implementation of FAST-PET/MRI for whole-body staging of female patients with recurrent pelvic malignancies: A comparison to PET/CT.

Author

Grueneisen J, Schaarschmidt BM, Heubner M, Suntharalingam S, Milk I, Kinner S, Heubner A, Forsting M, Lauenstein T, Ruhlmann V, and Umutlu L

Subjects
Adult, Aged, Female, Humans, Middle Aged, Neoplasm Staging, Observer Variation, Pelvis diagnostic imaging, Pelvis pathology, Reproducibility of Results, Sensitivity and Specificity, Whole Body Imaging methods, Magnetic Resonance Imaging methods, Multimodal Imaging methods, Neoplasm Recurrence, Local diagnosis, Pelvic Neoplasms diagnosis, Positron-Emission Tomography methods, Tomography, X-Ray Computed methods
Abstract

Objectives: To compare the diagnostic competence of FAST-PET/MRI and PET/CT for whole-body staging of female patients suspect for a recurrence of a pelvic malignancy., Methods: 24 female patients with a suspected tumor recurrence underwent a PET/CT and subsequent PET/MRI examination. For PET/MRI readings a whole-body FAST-protocol was implemented. Two readers separately evaluated the PET/CT and FAST PET/MRI datasets regarding identification of all tumor lesions and qualitative assessment of visual lesion-to-background contrast (4-point ordinal scale)., Results: Tumor relapse was present in 21 of the 24 patients. Both, PET/CT and PET/MRI allowed for correct identification of tumor recurrence in 20 of 21 cases. Lesion-based sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the detection of malignant lesions were 82%, 91%, 97%, 58% and 84% for PET/CT and 85%, 87%, 96%, 63% and 86% for PET/MRI, lacking significant differences. Furthermore, no significant difference for lesion-to-background contrast of malignant and benign lesions was found., Conclusion: FAST-PET/MRI provides a comparably high diagnostic performance for restaging gynecological cancer patients compared to PET/CT with slightly prolonged scan duration, yet enabling a markedly reduced radiation exposure., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Published
2015
Full Text
View/download PDF

45. Integrated PET/MRI for whole-body staging of patients with primary cervical cancer: preliminary results.

Author

Grueneisen J, Schaarschmidt BM, Heubner M, Aktas B, Kinner S, Forsting M, Lauenstein T, Ruhlmann V, and Umutlu L

Subjects
Adult, Aged, Female, Humans, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Uterine Cervical Neoplasms diagnostic imaging, Magnetic Resonance Imaging, Multimodal Imaging, Positron-Emission Tomography, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms pathology, Whole Body Imaging
Abstract

Purpose: To assess the diagnostic value of integrated PET/MRI for whole-body staging of cervical cancer patients, as well as to investigate a potential association between PET/MRI derived functional parameters and prognostic factors of cervical cancer., Methods: The present study was approved by the local institutional review board. Twenty-seven patients with histopathologically confirmed cervical cancer were prospectively enrolled in our study. All patients underwent a whole-body PET/MRI examination after written informed consent was obtained. Two radiologists separately evaluated the PET/MRI data sets regarding the determination of local tumor extent of primary cervical cancer lesions, as well as detection of nodal and distant metastases. Furthermore, SUV and ADC values of primary tumor lesions were analyzed and correlated with dedicated prognostic factors of cervical cancer. Results based on histopathology and cross-sectional imaging follow-up served as the reference standard., Results: PET/MRI enabled the detection of all 27 primary tumor lesions of the uterine cervix and allowed for the correct determination of the T-stage in 23 (85 %) out of the 27 patients. Furthermore, the calculated sensitivity, specificity and diagnostic accuracy for the detection of nodal positive patients (n = 11) were 91 %, 94 % and 93 %, respectively. PET/MRI correctly identified regional metastatic disease (N1-stage) in 8/10 (80 %) patients and non-regional lymph node metastases in 5/5 (100 %) patients. In addition, quantitative analysis of PET and MRI derived functional parameters (SUV; ADC values) revealed a significant correlation with pathological grade and tumor size (p < 0.05)., Conclusions: The present study demonstrates the high potential of integrated PET/MRI for the assessment of primary tumor and the detection of lymph node metastases in patients with cervical cancer. Providing additional prognostic information, PET/MRI may serve as a valuable diagnostic tool for cervical cancer patients in a pretreatment setting.

Published
2015
Full Text
View/download PDF

46. Diagnostic value of diffusion-weighted imaging in simultaneous 18F-FDG PET/MR imaging for whole-body staging of women with pelvic malignancies.

Author

Grueneisen J, Schaarschmidt BM, Beiderwellen K, Schulze-Hagen A, Heubner M, Kinner S, Forsting M, Lauenstein T, Ruhlmann V, and Umutlu L

Subjects
Adult, Aged, Diffusion Magnetic Resonance Imaging, False Negative Reactions, Female, Humans, Middle Aged, Pelvic Neoplasms diagnostic imaging, Positron-Emission Tomography, Predictive Value of Tests, Multimodal Imaging methods, Neoplasm Staging methods, Pelvic Neoplasms diagnosis, Whole Body Imaging methods
Abstract

Unlabelled: The aim of this study was to assess the diagnostic benefit of diffusion-weighted imaging (DWI) in an (18)F-FDG PET/MR imaging protocol for whole-body staging of women with primary or recurrent malignancies of the pelvis., Methods: Forty-eight patients with a primary pelvic malignancy or suspected recurrence of a pelvic malignancy were included in our study. All patients underwent a whole-body (18)F-FDG PET/MR imaging examination that included DWI. Two radiologists separately evaluated the PET/MR imaging datasets without DWI followed by a second interpretation with DWI. First, both readers identified all primary tumors, as well as lymph node and distant metastases. In a second session, PET and DWI data were assessed qualitatively. Image interpretation comprised lesion conspicuity defined as visual lesion-to-background contrast (4-point ordinal scale) and diagnostic confidence (3-point ordinal scale) for all tumors. The results from histopathologic examination and cross-sectional imaging follow-up (≥6 mo) were used as the reference standard. Statistical analysis was performed to assess the significance of differences between obtained values., Results: Among the 122 suspected lesions seen, 98 (80.3%) were considered malignant. PET/MR imaging without DWI had a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 92.9%, 87.5%, 96.8%, 75.0%, and 91.8%, respectively, for the detection of malignant lesions. PET/MR imaging with DWI had slightly higher values (94.9%, 83.3%, 95.9%, 80.0%, and 92.6%, respectively), but the difference was not significant (P > 0.05). In the qualitative assessment of lesion-to-background contrast, PET had significantly (P < 0.05) higher values (3.79 ± 0.58) than DWI (3.63 ± 0.77). Furthermore, significantly (P < 0.05) higher scores were found for diagnostic confidence using PET (2.68 ± 0.64) for the determination of malignant lesions, when compared with DWI (2.53 ± 0.69)., Conclusion: DWI in PET/MR imaging has no diagnostic benefit for whole-body staging of women with pelvic malignancies. The omission of DWI for staging or restaging gynecologic cancer may significantly reduce examination times, thus increasing patient comfort without a relevant decrease in diagnostic competence., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Published
2014
Full Text
View/download PDF

47. Simultaneous positron emission tomography/magnetic resonance imaging for whole-body staging in patients with recurrent gynecological malignancies of the pelvis: a comparison to whole-body magnetic resonance imaging alone.

Author

Grueneisen J, Beiderwellen K, Heusch P, Gratz M, Schulze-Hagen A, Heubner M, Kinner S, Forsting M, Lauenstein T, Ruhlmann V, and Umutlu L

Subjects
Adult, Aged, Cervix Uteri diagnostic imaging, Cervix Uteri pathology, Contrast Media, Female, Fluorodeoxyglucose F18, Humans, Image Enhancement methods, Image Processing, Computer-Assisted methods, Middle Aged, Observer Variation, Ovarian Neoplasms diagnosis, Ovary diagnostic imaging, Ovary pathology, Prospective Studies, Reproducibility of Results, Uterine Cervical Neoplasms diagnosis, Young Adult, Genital Neoplasms, Female diagnosis, Magnetic Resonance Imaging methods, Multimodal Imaging methods, Neoplasm Recurrence, Local diagnosis, Positron-Emission Tomography methods, Whole Body Imaging methods
Abstract

Objectives: The objective of this study was to assess the diagnostic value of integrated positron emission tomography/magnetic resonance imaging (PET/MRI) for whole-body staging of patients with recurrent gynecological pelvic malignancies, in comparison to whole-body MRI alone., Materials and Methods: The study was approved by the local institutional ethics committee. Written informed consent was obtained before each examination. Thirty-four consecutive patients with a suspected recurrence of cervical (n = 18) or ovarian (n = 16) cancer were prospectively enrolled for an integrated PET/MRI examination, which comprised a diagnostic, contrast-enhanced whole-body MRI protocol including dedicated sagittal dynamic imaging of the pelvis. Two radiologists separately evaluated the data sets regarding lesion count, lesion detection, lesion characterization, and diagnostic confidence. Mean and median values were calculated for each rating. Statistical analyses were performed both per-patient and per-lesion bases using a Wilcoxon signed-rank test to indicate potential significant differences among PET/MRI and MRI (alone) data sets., Results: Malignant lesions were present in 25 of the 34 patients. Positron emission tomography/magnetic resonance imaging offered correct and superior identification of all 25 patients with cancer recurrence, compared with MRI alone (23/25). A total of 118 lesions (malignant, 89; benign, 29) were detected. Positron emission tomography/magnetic resonance imaging correctly identified 88 (98.9%) of 89 malignant lesions, whereas MRI alone allowed for correct identification of 79 (88.8%) of the 89 malignant lesions. In addition, PET/MRI provided significantly higher lesion contrast and diagnostic confidence in the detection of malignant lesions (P < 0.001) compared with MRI alone., Conclusions: These first results demonstrate the high diagnostic potential of integrated PET/MRI for the assessment of recurrence of female pelvic malignancies compared with MRI alone.

Published
2014
Full Text
View/download PDF

48. The haplotype of three polymorphisms in the SATB1 promoter region impacts survival in breast cancer patients.

Author

Heubner M, Kimmig R, Aktas B, Siffert W, and Frey UH

Abstract

Special AT-rich sequence binding protein 1 (SATB1) has regulatory effects on gene expression and appears to play an important role in tumor progression. The present study screened the promoter region of the SATB1 gene for polymorphisms, evaluated the corresponding haplotypes regarding alterations in promoter activity in vitro and analyzed the impact of these haplotypes on the clinical course of breast cancer patients. A cohort of 241 female Caucasian breast cancer patients who had been treated was enrolled in this retrospective analysis. The median follow-up time was 93 months (range, 4-155 months). PCR products from DNA of 10 healthy, unrelated volunteers were analyzed to identify new polymorphisms within the promoter region. Genotyping was conducted using restriction fragment length polymorphism and pyrosequencing. PCR constructs with the respective alleles from the four most frequent haplotypes were cloned into the vector pGEM ® -T Easy and then transferred into the luc2 -containing reporter vector pGl 4.10 ® for transfection of HEK293 cells. The pGl 4.73 ® vector, containing hRluc , was used for normalizing the transfection rates. Sequencing the region -3807 to -2828 bp upstream of ATG from ten healthy blood donors, three single nucleotide polymorphisms consisting of base exchanges were identified: -3600T>C, -3363A>G and -2984C>T. The SATB1 -3600T/-3363A/-2984C haplotype had lower promoter activity than all other constructs in vitro and exhibited a significant association with nodal status (P<0.05). Kaplan-Meier survival analysis revealed significantly improved overall survival for homozygous SATB1 -3600T/-3363A/-2984C haplotype carriers compared with heterozygous carriers or the other haplotypes (P=0.033). The SATB1 -3600T/-3363A/-2984C haplotype is associated with lower promoter activity and appears to impact upon survival in breast cancer patients.

Published
2014
Full Text
View/download PDF

49. Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX ® , clinicopathological markers and tumor cell dissemination in the blood and bone marrow.

Author

Aktas B, Bankfalvi A, Heubner M, Kimmig R, and Kasimir-Bauer S

Abstract

The Oncotype DX ® assay is a validated genomic test that predicts the likelihood of breast cancer recurrence, patient survival within ten years of diagnosis and the benefit of chemotherapy in early-stage, node-negative, estrogen receptor-positive breast cancer. Further markers of recurrence include disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood, particularly stemness-like tumor cells (slCTCs). In this study, Oncotype DX, DTCs, CTCs and slCTCs were used to evaluate the risk of recurrence in 68 patients with human epidermal growth factor receptor 2-negative, early-stage breast cancer. Formalin-fixed, paraffin-embedded tissue sections were analyzed for the expression of 16 cancer genes and 5 reference genes by Oncotype DX, yielding a recurrence score (RS). G2 tumors were evaluated for urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor type 1 (PAI1) and Ki-67. Two BM aspirates were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. CTCs and slCTCs in the blood were detected using the AdnaTest BreastCancer, AdnaTest EMT and the AdnaTest TumorStemCell. Oncotype DX was performed in 68 cases, yielding a low RS in 30/68 patients (44%), an intermediate RS in 29/68 patients (43%) and a high RS in 9/68 patients (13%). DTCs were detected in 19/68 patients (28%), CTCs in 13/68 patients (19%) and slCTCs in 26/68 (38%) patients. Moreover, 8/68 patients (12%) with G2 tumors were positive for uPA, 6/68 (9%) for PAI1 and 21/68 (31%) for Ki-67. Ki-67, progesterone receptor (PR) and G3 tumors were significantly correlated with RS (P<0.001; P=0.006; and P=0,002, respectively), whereas no correlation was identified between DTCs, CTCs, slCTCs and RS. Ki-67 may support therapeutic decisions in cases where Oncotype DX is not feasible. Larger patient cohorts are required to estimate the additional detection of DTCs and CTCs for the determination of risk recurrence.

Published
2013
Full Text
View/download PDF

50. Definition of compartment-based radical surgery in uterine cancer: radical hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M Höckel translated to robotic surgery (rTMMR).

Author

Kimmig R, Wimberger P, Buderath P, Aktas B, Iannaccone A, and Heubner M

Subjects
Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Staging, Postoperative Complications, Prognosis, Uterine Cervical Neoplasms pathology, Hysterectomy, Mesoderm surgery, Robotics, Uterine Cervical Neoplasms surgery
Abstract

Background: Radical hysterectomy has been developed as a standard treatment in Stage I and II cervical cancers with and without adjuvant therapy. However, there have been several attempts to standardize the technique of radical hysterectomy required for different tumor extension with variable success. Total mesometrial resection as ontogenetic compartment-based oncologic surgery - developed by open surgery - can be standardized identically for all patients with locally defined tumors. It appears to be promising for patients in terms of radicalness as well as complication rates. Robotic surgery may additionally reduce morbidity compared to open surgery. We describe robotically assisted total mesometrial resection (rTMMR) step by step in cervical cancer and present feasibility data from 26 patients., Methods: Patients (n = 26) with the diagnosis of cervical cancer were included. Patients were treated by robotic total mesometrial resection (rTMMR) and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for FIGO stage IA-IIB cervical cancer., Results: No transition to open surgery was necessary. No intraoperative complications were noted. The postoperative complication rate was 23%. Within follow-up time (mean: 18 months) we noted one distant but no locoregional recurrence of cervical cancer. There were no deaths from cervical cancer during the observation period., Conclusions: We conclude that rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment-defined cervical cancer.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results