Publications by authors named "Intidhar Labidi Galy"

18 Publications

  • Page 1 of 1

Endometriosis-associated ovarian carcinomas: insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review.

Ann Transl Med 2020 Dec;8(24):1712

Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, Kent, UK.

Endometriosis is a benign gynecologic condition affecting up to one woman out of ten of reproductive age. It is defined by the presence of endometrial-like tissue in localizations outside of the uterine cavity. It often causes symptoms such as chronic pain, most frequently associated with the menstrual cycle, and infertility, but may also be oligo- or asymptomatic. There is evidence that some ovarian carcinoma (OC) histotypes, mainly the ovarian clear cell (OCCC) and endometrioid (EnOC) carcinoma, may arise from endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interacting domain containing protein 1A () gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which frequently co-occur. In ARID1A deficient cancers preclinical experimental data suggest different targetable mechanisms including epigenetic regulation, cell cycle, genomic instability, the PI3K/AKT/mTOR pathway, inflammatory pathways, immune modulation, or metabolic alterations as potential precision oncology approaches. Most of these strategies are relying on the concept of synthetic lethality in which tumors deficient in ARID1A are more sensitive to the different compounds. Some of these approaches are currently being or have recently been investigated in early clinical trials. The remarkably frequent occurrence of these mutations in endometriosis-associated ovarian cancer, the occurrence in a relatively young population, and the high proportion of platinum-resistant disease certainly warrants further investigation of precision oncology opportunities in this population. Furthermore, advanced knowledge about oncogenic mutations involved in endometriosis-associated ovarian carcinomas may be potentially useful for early cancer detection. However, this approach may be complicated by the frequent occurrence of somatic mutations in benign endometriotic tissue as recent studies suggest. In this narrative review of the current literature, we will discuss the data available on endometriosis-associated ovarian carcinoma, with special emphasis on epidemiology, diagnosis and molecular changes that could have therapeutic implications and clinical applicability in the future.
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http://dx.doi.org/10.21037/atm-20-3022aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812165PMC
December 2020

Challenges for immunotherapy for the treatment of platinum resistant ovarian cancer.

Semin Cancer Biol 2020 Sep 12. Epub 2020 Sep 12.

Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland; Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address:

Platinum resistant ovarian cancer, usually defined as progression occurring within 6 months after completing platinum-based therapy, is a heterogeneous disease with poor prognosis and short survival (less than 18 months). It is typically considered as a "cold tumor", characterized by reduced infiltration by immune cells, particularly CD8 T cells. Response rate to anti-PD1/PD-L1 monotherapy is low, not exceeding 8%. Multiple therapeutic strategies are currently investigated in order to increase response rates to anti-PD1/PD-L1 through adding chemotherapy, anti-angiogenic agents, DNA damage (PARP inhibitors, cyclophosphamide and/or radiotherapy) or other immune checkpoint inhibitors (CTLA-4, etc.). Ovarian clear cell carcinoma, a rare histotype characterized by primary platinum-resistance, recently showed anecdotal but promising response rates to immune checkpoint blockade. Other immunotherapeutic approaches such as adoptive T cell therapy, vaccines and targeting myeloid immune checkpoints like "don't eat me" signal CD47 are currently investigated. Each approach faces distinct challenges that will be reviewed here. Robust immunogenomics studies conducted in parallel of the ongoing trials will help into refining optimal immunotherapy combination for this lethal disease and identify predictive biomarkers.
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http://dx.doi.org/10.1016/j.semcancer.2020.08.017DOI Listing
September 2020

Sustained response to pembrolizumab without prior chemotherapy in high-grade serous ovarian carcinoma with mutation.

Gynecol Oncol Rep 2020 Aug 15;33:100600. Epub 2020 Jun 15.

Department of Oncology, Hôpitaux Universitaires de Genève, Genève, Switzerland.

•Metastatic mutated HGSOC showed objective and sustained response to pembrolizumab.•The tumor was massively infiltrated by CD8 T cells while PD-L1 TPS was at 10%.• mutated HGSOC showed up-regulation of and
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http://dx.doi.org/10.1016/j.gore.2020.100600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322246PMC
August 2020

Clinical outcome of breast cancer in carriers of BRCA1 and BRCA2 mutations according to molecular subtypes.

Sci Rep 2020 04 27;10(1):7073. Epub 2020 Apr 27.

Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.

BRCA1/BRCA2 genes play a central role in DNA repair and their mutations increase sensitivity to DNA-damaging agents. There are conflicting data regarding the prognostic value of BRCA germline mutations in breast cancer (BC) patients. We collected clinical, pathological and genetic data of a cohort 925 BC patients preselected for genetic screening and treated with neoadjuvant or adjuvant chemotherapy, of whom 266 were BRCA carriers. Overall, 171 women carried a BRCA1 mutation, 95 carried a BRCA2 mutation, and 659 were non-carriers. In the entire cohort, there was a prolonged disease-free survival (DFS) for BRCA carriers (hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.44-0.90 for BRCA1; HR = 0.72; 95%CI, 0.47-1.1 for BRCA2; p = 0.020) and a trend toward prolonged disease-specific survival (DSS; HR = 0.65; 95%CI, 0.40-1.1 for BRCA1; HR = 0.78; 95%CI, 0.44-1.38 for BRCA2; p = 0.19) though not statistically significant. In the TNBC group, BRCA carriers had prolonged DFS (adjusted HR = 0.50; 95%CI, 0.28-0.89 for BRCA1; adjusted HR = 0.37; 95%CI, 0.11-1.25, for BRCA2; p = 0.034) and DSS (adjusted HR = 0.42; 95%CI, 0.21-0.82 for BRCA1; adjusted HR = 0.45; 95%CI, 0.11-1.9 for BRCA2; p = 0.023). In the non-TNBC group, the BRCA1 or BRCA2 mutations did not have any impact on survival. These results suggest that BRCA1/BRCA2 germline mutations are associated with prolonged survival only if women were diagnosed with TNBC.
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http://dx.doi.org/10.1038/s41598-020-63759-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184602PMC
April 2020

Immunologic Clearance of a BK Virus-associated Metastatic Renal Allograft Carcinoma.

Transplantation 2021 02;105(2):423-429

Abdominal Transplant Surgery, Department of Surgery, Geneva University Hospital and University of Geneva Medical School, Geneva, Switzerland.

Background: Metastatic carcinoma of a renal allograft is a rare but life threatening event with a difficult clinical management. Recent reports suggested a potential role of BK polyomavirus (BKPyV) in the development of urologic tract malignancies in kidney transplant recipients.

Methods: We investigated a kidney-pancreas female recipient with an history of BKPyV nephritis who developed a rapidly progressive and widely metastatic donor-derived renal carcinoma 9 years after transplantation.

Results: Histology and fluorescence in situ hybridization analysis revealed a donor-derived (XY tumor cells) collecting (Bellini) duct carcinoma. The presence of BKPyV oncogenic large tumor antigen was identified in large amount within the kidney tumor and the bowel metastases. Whole genome sequencing of the tumor confirmed multiple genome BKPyV integrations. The transplanted kidney was removed, immunosuppression was withdrawn, and recombinant interleukin-2 (IL-2) was administered for 3 months, inducing a complete tumor clearance, with no evidence of disease at 6-year follow-up. The immunological profiling during IL-2 therapy revealed the presence of donor-specific T cells and expanded cytokine-producing bright natural killer cells but no donor-specific antibodies. Finally, we found persistently elevated anti-BK virus IgG titers and a specific anti-BKPyV T cell response.

Conclusions: This investigation showed evidence for the potential oncogenic role of BKPyV in collecting duct carcinoma in renal allografts and demonstrated that immunosuppression withdrawal and IL-2 therapy can lead to an efficient antitumor cellular mediated rejection possibly via 3 distinct mechanisms including (1) host-versus-graft, (2) host-versus-tumor, and (3) anti-BKPyV responses.
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http://dx.doi.org/10.1097/TP.0000000000003193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837753PMC
February 2021

Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis.

Gynecol Oncol 2020 02 18;156(2):377-386. Epub 2019 Nov 18.

Centre de recherche du Centre hospitalier de l'Université de Montreal (CRCHUM), and Institut du cancer de Montréal, Montreal, QC, Canada; Department of Medicine, University of Montreal, Montreal, QC, Canada. Electronic address:

Background: Carriers of pathogenic variants in both BRCA1 and BRCA2 genes as a double mutation (BRCA1/2 DM) have been rarely reported in women with epithelial ovarian cancer (EOC).

Methods: We reviewed the English literature and interrogated three repositories reporting EOC patients carrying BRCA1/2 DM. The clinicopathological parameters of 36 EOC patients carrying germline BRCA1/2 DM were compared to high-grade serous EOC women of the COEUR cohort with known germline BRCA1/BRCA2 mutation carrier status (n = 376 non-carriers, n = 65 BRCA1 and n = 38 BRCA2). Clinicopathological parameters evaluated were age at diagnosis, stage of disease, loss of heterozygosity, type of mutation, immunohistochemistry profile, progression occurrence and survival.

Results: Median age at diagnosis of BRCA1/2 DM patients was 51.9 years, similar to BRCA1 mutation carriers (49.7 years, p = .58) and younger than BRCA2 mutation carriers (58.1 years, p = .02). Most patients were diagnosed at advanced stage (III-IV; 82%) and were carriers of founder/frequent mutations (69%). Tissue immunostainings revealed no progesterone receptor expression and low intraepithelial inflammation. The 5-year survival rate (60%) was significantly lower than that of BRCA2 mutation carriers (76%, p = .03) but not of BRCA1 mutation carriers (51%, p = .37).

Conclusions: Our data suggests some co-dominant effect of both mutations but the outcome of these patients more closely resembled that of BRCA1 mutation carriers with poor prognosis factors.
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http://dx.doi.org/10.1016/j.ygyno.2019.11.019DOI Listing
February 2020

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers.

Gynecol Oncol 2019 11 8;155(2):262-269. Epub 2019 Oct 8.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France; University Claude Bernard (UCBL Lyon1), Lyon, France.

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice.

Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy.

Results: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125.

Conclusions: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.
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http://dx.doi.org/10.1016/j.ygyno.2019.09.008DOI Listing
November 2019

BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients.

Breast Cancer Res Treat 2019 Apr 11;174(3):775-783. Epub 2019 Jan 11.

Department of Oncology, Hôpitaux Universitaires de Genève, 4 Rue Gabrielle Perret-Gentil, 1205, Geneva, Switzerland.

Purpose: BRCA1 and BRCA2 proteins are central to DNA repair process through homologous recombination. We hypothesize that BRCA1/BRCA2 mutation carriers may exhibit increased hematological toxicity when receiving genotoxic chemotherapy.

Methods: We included women with primary breast cancers screened for BRCA1/BRCA2 germline mutations and treated with (neo)adjuvant chemotherapy in Geneva (Swiss cohort). The primary endpoint was the incidence of febrile neutropenia following the first chemotherapy cycle (C1). Secondary endpoints were the incidence of grade 3-4 neutropenia, grade 4 neutropenia and hospitalization during C1, G-CSF use and chemotherapy dose reduction during the entire chemotherapy regimen. Long-term toxicities (hematological, cardiac and neuropathy) were assessed in the Swiss cohort and a second cohort of patients from Lyon (French cohort).

Results: Overall, 221 patients were assessed for acute hematological toxicity, including 23 BRCA1 and 22 BRCA2 carriers. Following the C1, febrile neutropenia had an incidence of 35% (p = 0.002), 14% (p = 0.562) and 10% among BRCA1, BRCA2 and non-carriers, respectively. Grade 4 neutropenia was found in 57% of BRCA1 (p < 0.001), 14% of BRCA2 (p = 0.861) and 18% of non-carriers. G-CSF support was necessary in 86% of BRCA1 (p = 0.005), 64% of BRCA2 (p = 0.285) and 51% of non-carriers. For long-term toxicity analysis, 898 patients were included (167 BRCA1-, 91 BRCA2- and 640 non-carriers). There was no difference between the 3 groups.

Conclusions: BRCA1 germline mutations is associated with greater acute hematological toxicity in breast cancer patients. These observations could have implication for primary prophylaxis with G-CSF.
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http://dx.doi.org/10.1007/s10549-018-05127-2DOI Listing
April 2019

Location of Mutation in Gene and Survival in Patients with Ovarian Cancer.

Clin Cancer Res 2018 01 30;24(2):326-333. Epub 2017 Oct 30.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of gene affects the clinical outcome of ovarian cancer patients. A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for and genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer ( = 316) was used as a validation cohort. In the study cohort, 78 patients were carriers of germline mutations of After adjustment for FIGO stage and macroscopic residual disease, carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; = 0.001] and prolonged PFI (29.7 vs. 15.5 months, = 0.011), compared with noncarriers. carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; = 0.094) or PFI (19 vs. 15.5 months, = 0.146). In the TCGA cohort, only carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; = 0.001). Among ovarian cancer patients, carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2136DOI Listing
January 2018

High grade serous ovarian carcinomas originate in the fallopian tube.

Nat Commun 2017 10 23;8(1):1093. Epub 2017 Oct 23.

Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.

High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.
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http://dx.doi.org/10.1038/s41467-017-00962-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5653668PMC
October 2017

[Screening of ovarian cancer : not for tomorrow].

Rev Med Suisse 2017 May;13(563):1039-1041

Service d'oncologie, Département d'oncologie, HUG, 1211 Genève 14.

As the worldwide incidence of cancer continuously rises, one of the measures to reduce mortality is early diagnosis while the disease is still curable. Colonoscopy screening and PAP-smears are worthwhile examples illustrating the impact of early diagnosis on mortality. Ovarian cancer is the first cause of mortality by gynecological cancers in Switzerland (incidence of 600 new cases / year), mostly diagnosed at advanced stages with a poor prognosis. Could surveillance measures improve survival ? Three large-scale randomized control trials failed to show mortality reduction from ovarian cancer with the methods currently available. A better comprehension of pathogenesis can allow the development of new strategies of screening.
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May 2017

Clinical Development of Anti-mitotic Drugs in Cancer.

Adv Exp Med Biol 2017 ;1002:125-152

Department of Oncology, Geneva University Hospitals, Rue Gabrielle Perret-Gentil 4, Geneva, 1205, Switzerland.

Mitosis is one of the most fundamental processes of life by which a mammalian cell divides into two daughter cells. Mitosis has been an attractive target for anticancer therapies since fast proliferation was identified as one of the hallmarks of cancer cells. Despite efforts into developing specific inhibitors for mitotic kinases and kinesins, very few drugs have shown the efficiency of microtubule targeting-agents in cancer cells with paclitaxel being the most successful. A deeper translational research accompanying clinical trials of anti-mitotic drugs will help in identifying potent biomarkers predictive for response. Here, we review the current knowledge of mitosis targeting agents that have been tested so far in the clinics.
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http://dx.doi.org/10.1007/978-3-319-57127-0_6DOI Listing
September 2017

Ovarian cancer: Status of homologous recombination pathway as a predictor of drug response.

Crit Rev Oncol Hematol 2016 May 27;101:50-9. Epub 2016 Feb 27.

Center of Oncology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland. Electronic address:

Epithelial ovarian cancer (EOC), particularly high-grade serous subtype, is associated with germline mutations in BRCA1/BRCA2 genes in up to 20% of the patients. BRCA1/BRCA2 proteins are important components of the homologous recombination (HR) pathway, a vital DNA repair process that protects the genome from double-strand DNA damage. Recent studies revealed frequent somatic mutations of BRCA1/BRCA2 and hypermethylation of the promoter of BRCA1 in EOC, in addition to germline mutations. Comparison of DNA copy number changes in tumors with or without BRCA1/BRCA2 alterations, lead to the identification of several signatures that detect HR pathway defects, here named "HRness". These signatures predict platinum-sensitivity and survival in EOC, as it was previously shown for germline mutations of BRCA1/BRCA2. They are currently investigated in clinical trials as potential predictive biomarker for response to poly(ADP- ribose) polymerase inhibitors.
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http://dx.doi.org/10.1016/j.critrevonc.2016.02.014DOI Listing
May 2016

Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer.

Gynecol Oncol 2014 Mar 23;132(3):542-50. Epub 2014 Jan 23.

Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115, USA; Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address:

Objective: To investigate the neutrophil-to-lymphocyte ratio (NLR) from peripheral blood, a general measure of inflammation, in ovarian cancer.

Methods: White cell counts and CA125 levels before treatment, tumor features, and questionnaire data on 519 women with ovarian cancer at two Boston hospitals were recorded. Counts were log-transformed and effects on these by tumor features and epidemiologic variables assessed by analysis of variance and generalized linear models. Cox proportional hazards models were used to assess effects on overall survival.

Results: Greater NLR was associated with higher tumor stage and grade, presence of ascites, and bilateral disease and correlated with risk factors including Jewish ethnicity, taller height, more ovulatory cycles, and family history of cancer in premenopausal women and talc use in all women. CA125 was positively correlated with neutrophil count, monocyte count, and NLR and inversely correlated with lymphocyte count. In a multivariate adjusted analysis, high NLR predicted poorer survival and high lymphocyte count better survival.

Conclusion: An elevated NLR before treatment signals more aggressive disease and correlates with risk factors for ovarian cancer. CA125 directly correlates with neutrophils which may reflect secretion of both CA125 and neutrophilic growth factors by the tumor. CA125 inversely correlates with lymphocytes which may reflect the ability of some neutrophilic factors to induce lymphopenia and/or binding of CA125 to lymphocytes removing CA125 from the serum pool. Links between NLR, CA125, and epidemiologic factors may provide new clues about the pathogenesis and progression of ovarian cancer.
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http://dx.doi.org/10.1016/j.ygyno.2014.01.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980949PMC
March 2014

Prior appendectomy does not protect against subsequent development of malignant or borderline mucinous ovarian neoplasms.

Gynecol Oncol 2014 Feb 14;132(2):328-33. Epub 2013 Dec 14.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Department of Pathology, Boston, MA, USA; Brigham and Women's Hospital, Division of Women's and Perinatal Pathology, Boston, MA, USA. Electronic address:

Background: Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking.

Methods: The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry.

Results: From the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas.

Conclusion: Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases.

Funding: National Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman 'Tina's Wish' Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute - Susan Smith Center for Women's Cancers; Robert and Deborah First Fund; The Gamel Family Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France.
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http://dx.doi.org/10.1016/j.ygyno.2013.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929430PMC
February 2014

Lymphopenia combined with low TCR diversity (divpenia) predicts poor overall survival in metastatic breast cancer patients.

Oncoimmunology 2012 Jul;1(4):432-440

ImmunID Technologies; CEA; Grenoble, France ; Université Lyon 1; ISPB; Lyon, France ; Team 11; CRCL INSERM U-1052/CNRS 5286; Lyon, France ; LabEx DEVweCAN; Centre Léon Bérard; Lyon, France.

Lymphopenia (< 1Giga/L) detected before initiation of chemotherapy is a predictive factor for death in metastatic solid tumors. Combinatorial T cell repertoire (TCR) diversity was investigated and tested either alone or in combination with lymphopenia as a prognostic factor at diagnosis for overall survival (OS) in metastatic breast cancer (MBC) patients. The combinatorial TCR diversity was measured by semi quantitative multi-N-plex PCR on blood samples before the initiation of the first line chemotherapy in a development (n = 66) and validation (n = 67) MBC patient cohorts. A prognostic score, combining lymphocyte count and TCR diversity was evaluated. Univariate and multivariate analyses of prognostic factors for OS were performed in both cohorts. Lymphopenia and severe restriction of TCR diversity called "divpenia" (diversity ≤ 33%) were independently associated with shorter OS. Lympho-divpenia combining lymphopenia and severe divpenia accurately identified patients with poor OS in both cohorts (7.6 and 10.6 vs 24.5 and 22.9 mo). In multivariate analysis including other prognostic clinical factors, lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (p = 0.005) along with lack of HER2 and hormonal receptors expression (p = 0.011) and anemia (p = 0.009). Lympho-divpenia is a novel prognostic factor that will be used to improve quality of MBC patients' medical care.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382902PMC
http://dx.doi.org/10.4161/onci.19545DOI Listing
July 2012

Bevacizumab plus microtubule targeting agents in heavily pre-treated ovarian cancer patients: a retrospective study.

Bull Cancer 2011 Oct;98(9):80-9

CHU Hautepierre, Department of Oncology & Hematology, Strasbourg, France.

OBJECTIVES. As vascular endothelial growth factor (VEGF) is expressed in ovarian cancer, we assessed the efficacy and safety of bevacizumab (a monoclonal antibody targeting VEGF) plus microtubule targeting agents for heavily pre-treated ovarian carcinoma patients. METHODS. We retrospectively reviewed 43 patients with recurrent epithelial ovarian carcinoma. Combined treatment included bevacizumab with paclitaxel in 32 (74%), docetaxel in 10 (23%), and vinorelbine in one (2.3%) patients, respectively. RESULTS. The median number of combined treatment was six cycles (range 1-29). On RECIST criteria, the objective response rate (ORR) was 40% (16% CR and 24% PR). Clinical benefit (complete response [CR] plus partial response [PR] and stable disease [SD] lasting ≥ 3 months) was 74% (CI95%: 46.7-77%). Median duration of treatment and overall survival were 3.9 months (range 0.2-14.4 months) and 20.1 months (CI95%: 13.8-20.1) respectively. No toxic death was reported. Grade 3-4 toxicity occurred in 30% of patients. Gastrointestinal perforations and fistula occurred in 3 (7%) and 6 (14%) patients, respectively. CONCLUSION. Although being active in terms of ORR, bevacizumab plus microtubule targeting agents - mainly taxanes - leads to a high rate of gastro-intestinal perforations and fistula in heavily pre-treated ovarian carcinoma patients.
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http://dx.doi.org/10.1684/bdc.2011.1436DOI Listing
October 2011