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Ovarian cancer (OC) has a poor prognosis as most patients present with non-specific symptoms and the disease is mostly diagnosed at advanced stages. Approximately 90% of cases are classified as epithelial OC (EOC), a category comprising histologically and molecularly distinct tumours. Identifying reliable biomarkers and employing personalised therapies in OC subgroups is crucial for battling the disease. EOCs are often characterised by homologous recombination repair deficiency (HRD), frequently caused by inactivation of the breast cancer susceptibility (BRCA) genes. These findings have led to the development of poly- (adenosine diphosphate [ADP])- ribose polymerase inhibitors (PARPi), which are synthetically lethal to HRD tumour cells. Both patients with HRD and non-HRD tumours can benefit from PARPi therapy in the recurrent setting. Moreover, recent phase III trials in patients with newly diagnosed advanced-stage OC have demonstrated greater clinical benefit from PARPi in treating HRD than non-HRD tumours. These findings offer new opportunities for the use of PARPi as maintenance therapy after first-line chemotherapy based on the presence of HRD. In the current article, we provide recommendations for HRD testing and treatment of patients with newly diagnosed advanced-stage EOC. ispartof: FACTS VIEWS AND VISION IN OBGYN vol:14 issue:2 pages:111-120 ispartof: location:Belgium status: published

BACKGROUND Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days. Atezolizumab 1200 mg was given on day 1 and every 21 (±3) days thereafter. Treatment continued until patients experienced dose-limiting toxicity (DLT), had complete response, progressive disease, needed alternative anticancer treatment, or withdrew due to an adverse event (AE). The primary endpoint was DLT incidence, and secondary endpoints included efficacy and AEs. RESULTS Between 19 March 2018 and 6 November 2020, 11 patients with TNBC were enrolled (safety analysis set: n = 10); between 19 March 2018 and 16 October 2019, 25 patients with CRC were enrolled (safety analysis set: n = 24). For the 5 patients in the TNBC DLT analysis set, no patient had DLT; for the 18 patients in the CRC DLT analysis set, 3 (17%) had DLT, all serious AEs. AEs were reported by 9 (90%) TNBC and 23 (96%) CRC patients, the majority with grade ≥3 [TNBC, 7 (70%); CRC, 13 (54%)], and 1 was fatal [CRC, 1 (4%)]. Evidence of efficacy was limited. Overall response rate was 10% (95% confidence interval 0.3-44.5) for TNBC; one (10%) patient had a partial response. For CRC, no patients had a response; 14 (58%) were unassessable. CONCLUSIONS The safety profile reflected known risks with T-VEC including risks of intrahepatic injection; no unexpected safety findings from addition of atezolizumab to T-VEC were observed. Limited evidence of antitumor activity was observed.

BACKGROUND: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. DESIGN: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts' consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. CONCLUSION: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer. ispartof: ANNALS OF ONCOLOGY vol:33 issue:3 pages:276-287 ispartof: location:England status: published

Additional file 1: Table S1. Characteristics of patients who had SARS-CoV-2 RT-PCR. Table S2. Characteristics of patients diagnosed by SARS-CoV-2 serology (SARS-CoV-2 RT-PCR not performed or negative). Table S3. Adverse events with systemic therapy in the population with RT-PCR results. Table S4. Adverse events with systemic therapy in the population without or with negative RT-PCR results. Table S5. Landscape of treatment regimens the patients received and the number of grade 3–4 hematological adverse events, according to the SARS-CoV-2 status. Supplementary appendix 1: Framework used to notify adverse events at each cycle of anti-cancer treatment.

We report a case of a 67-years-old woman presenting a severe acute lymphocytic gastritis induced by pembrolizumab, an immune check point inhibitor (ICI). This gastritis was her third auto-immune adverse event after 5 years of treatment with pembrolizumab, it was metabolically active at the PET Scan and confirmed by analysis of the gastric biopsies. Pembrolizumab treatment cessation and high doses of corticosteroids completely normalized the stomach clinically, endoscopically and histologically. This patient was in complete remission of her metastatic melanoma. Therefore, pembrolizumab therapy was not restarted and the patient is still in remission 6 months later. This strategy is supported by recent publications describing a relapse rate inferior to 10% in patients in complete remission after 2 years of immunotherapy. Particularities of this case are: rareness of this adverse event, late onset after introduction of pembrolizumab, evocative PET scan image, specific endoscopic aspect and histology. In addition, the favorable oncologic evolution of the patient after treatment cessation confirms the prolonged remission after immunotherapy.

Most ovarian cancer patients are diagnosed only at advanced stages when survival outcomes are worse, andwhen therapeutic decisions might prove challenging. The fundamental treatment for women with ovarian cancerincludes debulking surgery whenever possible and appropriate systemic therapy (chemotherapy, targeted andantiangiogenic agents). In the last few years, knowledge about histological and molecular characteristics of ovariancancer subtypes and stages has increased considerably. This has enabled the development and improvement ofseveral options for the diagnosis and treatment of ovarian cancer in a patient-tailored approach. Accordingly,therapeutic decisions are guided by the characteristics of the patient and the tumour, especially the molecularfeatures of the cancer subtype and disease stage. Particularly relevant are the advances in early genetic testing ofgermline and somatic mutations involved in DNA repair, and the clinical development of targeted agents. In orderto implement the best individual medical strategies, in this article, we present an algorithm of treatment options,including recently developed targeted agents, for primary and recurrent ovarian cancer patients in Belgium. ispartof: FACTS VIEWS AND VISION IN OBGYN vol:12 issue:3 pages:227-239 ispartof: location:Belgium status: published

Introduction/Background Several studies suggest that oncological surgery induce an acute inflammatory response, and that it may exacerbate certain mechanisms related to tumor growth and eventual dissemination. We propose to investigates whether the administration of Ketorolac (Taradyl)®, a nonsteroidal anti-inflammatory drug, given intraoperatively during surgery for ovarian, tubal, or peritoneal cancer, influences disease free survival (DFS) and Overall survival (OS). Methodology A Retrospective analysis of all the patients operated at Cliniques Universitaires Saint-Luc; Brussel between 2015 and 2017 for ovarian, fallopian tube or peritoneum cancer. All the patient were included from the UCLouvain Network of Gynaecological Oncology (UNGO), an academic network in Belgium for centralisation of the surgery for ovarian cancer patient. Results Of the 90 patients who met the inclusion criteria, 68% received Ketorolac intraoperatively. Only age was statistically different between the two groups (p Conclusion These results suggest that the intraoperative administration of Ketorolac during surgery for ovarian, tubal or peritoneal cancer has a positive effect on the risk of recurrence and median survival. Disclosure Nothing to disclose.

Background: to study and compare ovarian function (clinical and biological data) among premenopausal breast cancer patients receiving tamoxifen alone (group I) or tamoxifen following chemotherapy (group II), because some studies suggest that amenorrhea is an insufficient parameter to define menopausal status. Material and methods: between 1999 and 2003, 138 premenopausal patients, treated for early breast cancer, were included: 68 patients in the group of tamoxifen alone and 70 patients in de group of tamoxifen administered after chemotherapy (6 cycles of FEC 100 on day 1 every 3 weeks -5 fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2- or 4 cycles of EC on day 1 every 3 weeks -epiadriamycine 75 mg/m2, cyclophosphamide 500 mg/m2-). All patients had a confirmed premenopausal status (biological data) at the entry of the study. The median age in group I was 44.5 (36 to 48) and 42 in group II (35 to 47.5). In group I, all were stage I and in group II, 34 were stage I and 36 were stage II. They were followed prospectively every 3 months for 3 years: date about menses, physical examination and blood tests (LH, FSH, 17-bêta-estradiol). Vaginal echography was added every 6 months. After 3 years, prospective evaluation was closed. Retrospective evaluation of all data was performed in 2009. Results: three patients were out of study in the group I and 2 were out of study in the group II. According to clinical data, patients were devided in 4 subgroups: a: regular menses (≥10 cycles/year) b: spaniomenorrhea (5 to 9 cycles/year) c: severe spaniomenorrhea (1 to 4 cycles/year) d: complete amenorrhea. The number of patients in each subgroup is respectively: - For group I (65 patients): 3 (4%), 19 (29%), 38 (58%) and 5 (8%). - For group II (68 patients): 2 (3%), 21 (30%), 38 (55%) and 7 (10%). The most interesting parameter to be studied wass the estradiol levels. Median values of estrogen levels For patients of subgroup a, tamoxifen mimicked an ovulatory cycle such as observed in patients receiving citrate of clomifen. For patients of subgroup b, the variations corresponded to nearly a normal ovulatory cycle. For patients of subgroups c and d, tamoxifen induced low levels of estradiol, LH and FSH, and very few variations. Estrogen levels did not to seem have an impact on disease free survival rate after 3 years of follow-up (100% in group I and 98.6% in group II and after 5 years (98.5% and 97%). In the two groups I and II, estrogen levels from patients of subgroups a and b were significantly higher than in subgroups c and d (p < 0.001). Conclusion: amenorrhea is an insufficient parameter to define menopausal status of patients receiving tamoxifen. Low estradiol level must be coupled to other biological parameters to characterize endocrine status. These data are very important in the choice of endocrine therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-13.

Ipilimumab is a human monoclonal antibody that blocks cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and promotes antitumour immunity. It has recently been approved for the treatment of metastatic melanoma patients. Ipilimumab is now widely used and the spectrum of side effects because of autoimmunity is expanding. To our knowledge, this is the first report of an ipilimumab-induced pulmonary immune-related adverse event (irAE) that was successfully treated by macrolides without corticosteroids.A 77-year-old man with metastatic melanoma developed fever, cough and dyspnoea soon after the start of ipilimumab treatment leading to the diagnosis of a bronchiolitis obliterans organising pneumonia (BOOP). The patient was treated with clarithromycin allowing a good clinical and radiological evolution.Macrolides seem to have a therapeutic anti-inflammatory potential in the case of mild to moderate pulmonary ipilimumab-induced irAEs. However, more data are needed to confirm macrolides use in this indication in clinical practice and corticosteroids remain the gold standard treatment in case of severe ipilimumab-associated irAEs.

Digital dermoscopy has been shown to permit an earlier detection of melanoma. However, few studies have investigated its added value in reducing unnecessary excisions in everyday clinical practice.To compare, in daily practice, the efficiency of three dermoscopy methods: dermoscopy alone with little training, dermoscopy alone with adequate training and dermoscopy with adequate training and access to digital dermoscopy, and to confirm the safety of this latter approach.Thirty-six dermatologists working without digital dermoscopy were divided into two groups according to their training in dermoscopy. The third group constituted of two dermatologists working in a pigmented lesion clinic with access to the digital dermoscopy technique and eight additional dermatologists working in the same dermatology department. These 46 dermatologists included all presumed melanocytic lesions excised over a period of 1 year. The primary endpoint was the melanoma/nonmelanoma ratio (M/NM-R); secondary endpoints were the ratio of 'problem' naevi to common naevi (PN/CN-R), specificity and sensitivity for the diagnosis of melanoma, in situ/invasive melanoma ratio, and the mean Breslow thickness.In total, 1865 excised lesions, including 231 melanomas, were included. In the digital dermoscopy availability group (DD-G) the M/NM-R was significantly better (1/2.43), as was the PN/CN-R (1/1.48) (P0.001 in both cases). The specificity was significantly higher in the DD-G and significantly higher for trained examiners as compared with examiners with little training. More that one-third of all melanomas discovered by digital dermoscopy were in situ, and the mean Breslow thickness was 0.32 mm for the invasive ones.The reduction of unnecessary excisions when using digital dermoscopy compared with dermoscopy alone in our study suggests that access to digital dermoscopy offers a better management of pigmented lesions in daily practice. The high number of early lesions diagnosed by this technique confirms that its use is safe.

The majority of human epithelial cancers is frequently characterized by a functional activation of the epidermal growth factor receptor (EGFR)-driven-pathways. Today, two classes of EGFR inhibitors are routinely used in the clinic: anti-EGFR monoclonal antibodies such as cetuximab and panitumumab and small-molecule inhibitors of the EGFR tyrosine kinase activity such as erlotinib and gefitinib. Anti-EGFR therapies have been approved in several countries for the treatment of metastatic nonsmall-cell lung cancer, colorectal cancer, squamous-cell carcinoma of the head and neck, and pancreatic cancer. This article summarizes the clinical evidence of the anticancer activity of anti-EGFR treatment, and considers the current, and controversial, clinical issues with respect to their optimal use in the treatment of patients with cancer. Mechanisms of resistance to anti-EGFR treatment are also briefly discussed.

We have identified an antigen recognized by autologous CTL on the lung carcinoma cells of a patient who enjoyed a favorable clinical evolution, being alive 10 years after partial resection of the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and encoded by a mutated sequence in the gene coding for malic enzyme, an essential enzyme that converts malate to pyruvate. In the tumor cell line derived from the patient, only the mutated malic enzyme allele is expressed, because of a loss of heterozygosity in the region of chromosome 6 that contains this locus. Tetramers of soluble HLA-A2 molecules loaded with the antigenic peptide stained approximately 0.4% of the patient's blood CD8 T cells. When these cells were stimulated in clonal conditions, 25% of them proliferated, and the resulting clones were lytic and specific for the mutated malic enzyme peptide. T-cell receptor analysis indicated that almost all of these antimalic CTLs shared the same receptor. Antimalic T cells were consistently found in blood samples collected from the patient between 1990 and 1999, at frequencies ranging from 0.1 to 0.4% of the CD8 cells. Their frequency appeared to double within 2 weeks after intradermal inoculation of lethally irradiated autologous tumor cells. These results indicate that nonmelanoma cancer patients may also have a high frequency of blood CTLs directed against a tumor-specific antigen.

We have identified an antigen recognized on a human large cell carcinoma by an autologous tumor-specific CTL clone that was derived from mononuclear cells infiltrating the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and is encoded by the alpha -actinin-4 gene, which is expressed ubiquitously. In the tumor cells, a point mutation generates an amino-acid change that is essential for recognition by the CTLs, The mutation was not found in alpha -actinin-4 cDNA sequences from about 50 lung carcinoma cell lines, suggesting that it is unique to this patient. Although he did not receive chemotherapy or radiotherapy, the patient has been without evidence of tumor since the resection of the primary lesion in 1996, Using tetramers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide, anti-alpha -actinin-4 CTLs could be derived from blood samples collected from the patient in 1998 and 2000, It is possible that these CTLs, recognizing a truly tumor-specific antigen, play a role in the clinical evolution of this lung cancer patient.

We describe a new HLA-C allele, Cw*0711, that differs from Cw*0704 by one residue in the intracytoplasmic region, and correct two errors in the published sequence of Cw*0501.