Nomogram Predicting the Likelihood of Parametrial Involvement in Early-Stage Cervical Cancer: Avoiding Unjustified Radical Hysterectomies

Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I and II—from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. Results: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86–0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. Conclusion: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping

European Society of Gynaecological Oncology quality indicators for surgical treatment of cervical cancer

Background: optimizing and ensuring the quality of surgical care is essential to improve the management and outcome of patients with cervical cancer.To develop a list of quality indicators for surgical treatment of cervical cancer that can be used to audit and improve clinical practice. Methods: quality indicators were developed using a four-step evaluation process that included a systematic literature search to identify potential quality indicators, in-person meetings of an ad hoc group of international experts, an internal validation process, and external review by a large panel of European clinicians and patient representatives. Results: fifteen structural, process, and outcome indicators were selected. Using a structured format, each quality indicator has a description specifying what the indicator is measuring. Measurability specifications are also detailed to define how the indicator will be measured in practice. Each indicator has a target which gives practitioners and health administrators a quantitative basis for improving care and organizational processes. Discussion: implementation of institutional quality assurance programs can improve quality of care, even in high-volume centers. This set of quality indicators from the European Society of Gynaecological Cancer may be a major instrument to improve the quality of surgical treatment of cervical cancer

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023*

Funding Information: Open access publishing supported by the National Technical Library in Prague. Funding Information: The authors thank ESGO, ESTRO, and ESP for their support. The authors also thank the 155 international reviewers (physicians and patient representatives, see Appendix 2 ) for their valuable comments and suggestions. The authors thank the ESGO office, especially Kamila Macku, Tereza Cicakova, and Kateřina Šibravová, provided invaluable logistical and administrative support throughout the process. Publisher Copyright: © 2023, ESGO, ESTRO, ESP.In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.publishersversionpublishe

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer – Update 2023

Funding Information: The authors thank ESGO, ESTRO, and ESP for their support. The authors also thank the 155 international reviewers (physicians and patient representatives, see Appendix 2 in Online Supplemental File 2) for their valuable comments and suggestions. The authors thank the ESGO office, especially Kamila Macku, Tereza Cicakova, and Kateřina Šibravová, provided invaluable logistical and administrative support throughout the process. The development group (including all authors) is collectively responsible for the decision to submit for publication. DC (chair), JL (chair), MRR (chair) and FP (methodologist) wrote the first draft of the manuscript. All other contributors have actively given personal input, reviewed the manuscript, and have given final approval before submission. DC is responsible for the overall content as the guarantor. Initiated through the ESGO the decision to develop multidisciplinary guidelines was made jointly by the ESGO, ESTRO, and ESP. The ESGO provided administrative support. The ESGO, ESTRO and ESP are nonprofit knowledgeable societies. *These guidelines were developed by ESGO, ESTRO and ESP and are published in the Int J Gynecol Cancer, Radiother Oncol and Virchows Archiv. CCh has reported advisory boards for GSK, MSD and EISAI; SFL has reported advisory boards for MSD, GSK, AstraZeneca and Novartis; DL has reported consultant honoria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen and PharmaMar, advisory boards for AstraZeneca, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept and Sutro, research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar, research sponsored by AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche, Seagen and Novartis, and speakers’ bureau activities for AstraZeneca, Clovis Oncology, GSK, MSD and PharmaMar; UM has reported advisory boards for AstraZeneca (Steering committee member for CALLA Study); RN has reported research grants from Elekta, Varian, Accuray, Dutch Research Council, and Dutch Cancer Society; AO has reported personal fees for advisory board membersip from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, F. Hoffmann-La Roche, Genmab/Seagen, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de Espana, SA, Mersana Thereapeutics, Novocure, PharmaMar, piIME Oncology, Roche, Sattucklabs, Sutro Biopharma and Tesaro, and personal fees for travel/accomodation from AstraZeneca, PharmaMar and Roche; DQ has reported advisory boards for Mimark inc; MPS has reported research grants and personal fees for workshops from Elekta AB; DC, MRR, FP, CC, AF, DF, DJK, FJ, CK, PM, RN, FPec, JP, SR, AS, VS, KT, IZ and JCL have reported no conflicts of interest. Not commissioned; internally peer reviewed. Not applicable. Not applicable. David Cibula, Maria Rosaria Raspollini, François Planchamp, Carlos Centeno, Cyrus Chargari, Ana Felix, Daniela Fischerova, Daniela Jahn-Kuch, Florence Joly, Christhardt Kohler, Sigurd F. Lax, Domenica Lorusso, Umesh Mahantshetty, Patrice Mathevet, Raj Naik, Remi Nout, Ana Oaknin, Fedro Peccatori, Jan Persson, Denis Querleu, Sandra Rubio, Maximilian Paul Schmid, Artem Stepanyan, Valentyn Svintsitskyi, Karl Tamussino, Ignacio Zapardiel, Jacob Christian Lindegaard. All data relevant to the study are included in the article or uploaded as supplementary information. Funding Information: CCh has reported advisory boards for GSK, MSD and EISAI; SFL has reported advisory boards for MSD, GSK, AstraZeneca and Novartis; DL has reported consultant honoria from AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Amgen, Seagen and PharmaMar, advisory boards for AstraZeneca, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept and Sutro, research institutional funding from Clovis Oncology, GSK, MSD and PharmaMar, research sponsored by AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Roche, Seagen and Novartis, and speakers’ bureau activities for AstraZeneca, Clovis Oncology, GSK, MSD and PharmaMar; UM has reported advisory boards for AstraZeneca (Steering committee member for CALLA Study); RN has reported research grants from Elekta, Varian, Accuray, Dutch Research Council, and Dutch Cancer Society; AO has reported personal fees for advisory board membersip from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, F. Hoffmann-La Roche, Genmab/Seagen, GSK, ImmunoGen, Itheos, Merck Sharp & Dohme de Espana, SA, Mersana Thereapeutics, Novocure, PharmaMar, piIME Oncology, Roche, Sattucklabs, Sutro Biopharma and Tesaro, and personal fees for travel/accomodation from AstraZeneca, PharmaMar and Roche; DQ has reported advisory boards for Mimark inc; MPS has reported research grants and personal fees for workshops from Elekta AB; DC, MRR, FP, CC, AF, DF, DJK, FJ, CK, PM, RN, FPec, JP, SR, AS, VS, KT, IZ and JCL have reported no conflicts of interest. Publisher Copyright: © 2023 ESGO, ESTRO, ESPIn 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer. To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives. These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.publishersversionpublishe

Comparative study of neoadjuvant chemotherapy with and without Zometa for management of locally advanced breast cancer with serum VEGF as primary endpoint: The NEOZOL study

Introduction Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. Materials and Methods We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. Results The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (−0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. Conclusion ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest

Apport clinique des biphosphonates dans les cancers du sein avancés (revue bibliographique et mise en place d'une étude d'évaluation)

LYON1-BU Santé (693882101) / SudocSudocFranceF

Papillomavirus humains et lésions précancéreuses du col utérin (implication de p53, Rb, cycline D1, PCNA, R-EGF, ras)

Les pouvoirs oncogéniques des papillomavirus humains (HPV) sont en relation avec la capacité des protéines virales E6 et E7 d'inactiver les gènes suppresseurs de tumeur p53 et Rb. Pour évaluer le processus de cancérogénèse du col utérin, nous avons étudié dans des dysplasies cervicales, l'expression de: PCNA, p53, pRb, cycline D1, récepteurs à EGF (R-EGF), ras et ARNm de E6-E7. Dans l'épithélium normal adjacent aux lésions et dans les régions condylomateuses, l'expression de P53, pRb, cyline D1, R-EGF et ras s'accroit parallèlement à une activité prolifératrice accrue révélée par PCNA. Dans les dysplasies, on observe une disparition de l'expression de p53 et de cycline D1 et une diminution de pRb. L'ARNm codant E6-E7, n'a été mis en évidence que dans les cellules superficielles de régions condylomateuses.Il existe donc une prolifération accrue avec une altération de l'expression de p53, pRb et cycline D1 dans l'épithélium normal adjacent aux dysplasies. L'action des HPV s'exerce dés les étapes initiales de la cancérogénèse. Il apparait trés probable que c'est l'action des protéines E6 et E7 d'HPV sur les cellules épithéliales basales et surtout parabasales qui est à l'origine de la dérégulation de la prolifération épithéliale et de l'apparition des signes de dysplasie.LYON1-BU Santé (693882101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Résultats de la chimiothérapie néoadjuvante dans les stades avancés de cancer de l'ovaire (stades III C et IV non résécables)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

The Clinical Impact of Low-Volume Lymph Nodal Metastases in Early-Stage Cervical Cancer: The Senticol 1 and Senticol 2 Trials

Background: With the development of the sentinel node technique in early-stage cervical cancer, it is imperative to define the clinical significance of micrometastases (MICs) and isolated tumor cells (ITCs). Methods: We included all patients who participated in the Senticol 1 and Senticol 2 studies. We analyzed the factors associated with the presence of low-volume metastasis, the oncological outcomes of patients with MIC and ITC and the correlation of recurrences and risk factors. Results: Twenty-four patients (7.5%) had low-volume metastasis. The risk factors associated with the presence of low-volume metastasis were a higher stage (p = 0.02) and major stromal invasion (p = 0.01) in the univariate analysis. The maximum specificity and sensitivity were found at a cutoff of 8 mm of stromal invasion. In multivariate analysis, the higher stage (p = 0.02) and the positive lymphovascular space invasion (p = 0.02) were significantly associated with the MIC and ITC. Patients with low-volume metastasis had similar disease-free survival (DFS) (92.7%) to node-negative patients (93.6%). The addition of adjuvant treatment in presence of low-volume metastasis did not modify the DFS. Conclusions: These results confirm our previous analysis of Senticol 1: the presence of low-volume metastasis did not decrease the DFS in early-stage cervical cancer patients