PD-L1 expression and PD-1/PD-L1 inhibitors in breast cancer

The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing). Its prognostic value remains controversial when assessed with immunohistochemistry, whereas it seems favorable in triple-negative cancers when assessed at the mRNA level. Early clinical trials with PD-1/PD-L1 inhibitors in breast cancer have shown efficacy in terms of tumor response and/or disease control in refractory metastatic breast cancers, notably in the triple-negative subtype. Many trials are currently underway, both in the metastatic and neo-adjuvant setting. A crucial issue is identification of biomarkers predictive of response to PD-1/PD-L1 inhibitors

The use of systemic therapies to prevent progression of inflammatory breast cancer: which targeted therapies to add on cytotoxic combinations?

International audienc

Traitements systémiques des cancers du sein inflammatoires : un état des lieux

International audienc

Dramatic and Delayed Response to Doxorubicin-Dacarbazine Chemotherapy of a Giant Desmoid Tumor: Case Report and Literature Review

Desmoid tumors are benign, slow-growing mesenchymal tumors. Aggressiveness is local with no potential for metastasis or dedifferentiation. The treatment is challenging, particularly in the case of huge intra-abdominal locations. We, herein, report on a 21-year-old patient with a giant intra-abdominal desmoid tumor occupying substantially the entire abdominal cavity. After failure of a first-line combination of celecoxib and tamoxifen, the patient was given doxorubicin-dacarbazine chemotherapy. The treatment was well tolerated, and rapidly, the clinical digestive symptoms improved. After 6 cycles, the computed tomography scan showed a partial response (regression of tumor volume by 55%). During follow-up, the tumor continued to regress: 25 months after the end of chemotherapy, the tumor volume had regressed by 95% when compared to the start of computed tomography and by 90% when compared to the end of chemotherapy. Thirty-three months after the diagnosis, the patient is alive without any symptom. Our case provides further evidence of the remarkable efficacy of a doxorubicin-dacarbazine regimen, especially in function- or life-threatening situations where a rapid response is required. We review the literature and discuss the challenging issue regarding treatment of desmoid tumors

Reversible rituximab-induced rectal Kaposi's sarcoma misdiagnosed as ulcerative colitis in a patient with HIV-negative follicular lymphoma

Background: Kaposi's sarcoma is a low-grade mesenchymal angioproliferative tumor, most commonly observed in immunocompromised individuals, such as HIV-infected patients. latrogenic Kaposi's sarcoma occurs in patients undergoing immunosuppressive therapies. Rituximab is a chimeric monoclonal antibody targeted against the pan B cell marker CD20. Because of its immunosuppressive effects through reduction of mature B-cells, it may exacerbate Kaposi's sarcoma in HIV-positive patients. Rituximab-related Kaposi's sarcomas have been previously reported in only two HIV-negative patients and were treated surgically. Case presentation: Here, we report on a Kaposi's sarcoma that developed under rituximab treatment in a HIV-negative 55-year-old patient treated for follicular lymphoma. The lesion developed during the maintenance rituximab therapy at the rectal level with an aspect of apparent ulcerative colitis, without any cutaneous lesion. The premature stop of rituximab led to the complete regression of Kaposi's sarcoma, without any additional specific treatment. Conclusions: To our knowledge, this is the third case of Kaposi's sarcoma diagnosed under rituximab in a HIV-negative patient, the first one at the rectal level and the first one that completely regresses after stop of rituximab. This case raises awareness of iatrogenic Kaposi's sarcoma in HIV-negative patients treated with rituximab, and further highlights the importance of immunosuppression in the pathophysiology of disease

Santé numérique et « cancer hors les murs », Big Data et intelligence artificielle

International audienceTo heal otherwise in oncology has become an imperative of Public Health and an economic imperative in France. Patients can therefore receive live most of their care outside of hospital with more ambulatory care. This ambulatory shift will benefit from the digital revolution and the development of digital health or e-health. Cancer research will also benefit with Big Data and artificial intelligence, which gather and analyze a huge amount of data. In this synthesis, we describe the different e-health tools and their potential impacts in oncology, at the levels of education and information of patients and caregivers, prevention, screening and diagnosis, treatment, follow-up, and research. A few randomized studies have already demonstrated clinical benefits. Large Big Data projects such as ConSoRe and Health Data Hub have been launched in France. We also discuss the issues and limitations of "cancer outside the hospital walls and e-health" from the point of view of patients, health care professionals, health facilities and government. This new organization will have to provide remote support "outside the walls" with care and follow-up of quality, continuous and prolonged in total safety and equity. Ongoing and future randomized clinical trials will need to definitively demonstrate areas of interest, advantages and drawbacks not only for patients, but also for caregivers, health facilities and governments.Soigner autrement en Cancérologie est devenu un impératif de Santé Publique et un impératif économique en France. Aujourd’hui, les patients peuvent vivre l’essentiel de leurs soins hors des murs de l’hôpital avec une prise en charge de plus en plus ambulatoire. Ce virage ambulatoire va bénéficier de la révolution numérique et du développement de la santé numérique ou e-santé. La recherche va également en bénéficier avec le Big Data et l’intelligence artificielle qui collectent en réseau et analysent une masse de données considérable. Dans cette Synthèse, nous décrivons les différents outils d’e-santé et leurs impacts potentiels en Cancérologie aux niveaux de l’éducation et l’information des patients et soignants, la prévention, le dépistage et le diagnostic, le suivi sous traitement, la surveillance et la recherche. Quelques études randomisées ont déjà démontré le bénéfice clinique. Des gros projets de Big Data tels que ConSoRe et Health Data Hub ont été mis en place en France. Nous discutons les enjeux et les limites du « cancer hors les murs et e-santé » du point de vue des patients, des professionnels de la santé, des établissements de santé et des pouvoirs publics. Cette nouvelle organisation devra permettre un accompagnement à distance « hors des murs » assurant soins et suivi de qualité, continus et prolongés en toute sécurité et équité. Les essais cliniques randomisés en cours et futurs devront démontrer de manière définitive les domaines d’intérêt, les avantages et inconvénients non seulement pour les patients, mais également pour les soignants, les établissements de santé et les pouvoirs publics

Metastatic Intimal Sarcoma of the Pulmonary Artery Sensitive to Carboplatin-Vinorelbine Chemotherapy: Case Report and Literature Review

Pulmonary artery intimal sarcoma (PAIS) is a very rare tumour with a very poor prognosis. In advanced stages, chemotherapy and radiotherapy are poorly efficient, and no standard chemotherapy guideline is currently available. Here, we report on a 37-year-old woman with PAIS initially treated with surgical resection who developed metastatic relapse refractory to anthracycline-based chemotherapy, then trabectedin, then pazopanib. The patient was then given carboplatin-vinorelbine chemotherapy. The treatment was well tolerated, and, rapidly, a CT scan showed an objective response that lasted 8 months despite the 4th therapeutic line. We review the literature and show that our case is the second one that provides evidence of the efficacy of platinum-vinorelbine regimens in this aggressive tumour. (C) 2018 The Author(s) Published by S. Karger AG, Base

Giant Pedunculated Hepatic Hemangioma: A Case Report and Literature Review

International audienceHepatic hemangioma is the most common benign hepatic tumor, and most of them are small in size and asymptomatic. Giant hepatic hemangiomas are uncommon, but pedunculated giant hemangiomas are even rarer and often difficult to diagnose because of their exophytic development. We report here on a 48-year-old man with a symptomatic pedunculated giant hepatic hemangioma and hepatic angiomatosis, mimicking a gastric gastrointestinal stromal tumor with liver metastases. The preoperative diagnosis was suspected on imaging including CT scan and MRI. The patient was successfully operated (left hepatic lobectomy), without any complication, and the pathological analysis confirmed the diagnosis. We reviewed the English literature, and to our knowledge, our case represents the largest case reported so far when compared with the 19 other informative cases

Outpatient Cancer Care Delivery in the Context of E-Oncology: A French Perspective on “Cancer outside the Hospital Walls”

International audienceIn oncology, the treatment of patients outside of hospitals has become imperative due to an increasing number of patients who are older and live longer, along with issues such as medical desertification, oncologist hyperspecialization, and difficulties in financing mounting health expenditures. Treatments have become less "invasive", with greater precision and efficiency. Patients can therefore receive most of their care outside of hospitals. The development of e-health can address these new imperatives. In this letter, we describe the different e-health tools and their potential clinical impacts in oncology, as already reported at every level of care, including education, prevention, diagnosis, treatment, and monitoring. A few randomized studies have yet demonstrated the clinical benefit. We also comment on issues and limits of "cancer outside the hospital walls" from the point of view of patients, health care professionals, health facilities, and public authorities. Care providers in hospitals and communities will have to adapt to these changes within well-coordinated networks in order to better meet patient expectations regarding increasing education and personalizing management. Ultimately, controlled studies should aim to definitively demonstrate areas of interest, benefits, and incentives, for not only patients, but also caregivers (formal and informal) and health care providers, health care facilities, and the nation

CSPG4 Expression in GIST Is Associated with Better Prognosis and Strong Cytotoxic Immune Response

Simple Summary Gastrointestinal stromal tumors (GIST) are the most frequent sarcomas of the gastrointestinal tract. Identification of novel prognostic and/or therapeutic targets is a major issue to overcome tyrosine kinase inhibitors resistances. CSPG4, a cell surface proteoglycan, emerged as a potential therapeutic target for immune therapy in different cancers, including sarcomas. CSPG4 expression has never been studied in GIST. In this work we analyzed CSPG4 mRNA expression in a large series of clinical GIST samples given the scarcity of disease (n = 309 patients). We find that high CSPG4 expression is independently associated with disease-free survival, and with an immune landscape favorable to induce strong cytotoxic immune response after NK cell stimulation. Our results suggest the potential value of CSPG4-specific chimeric antigen receptor-redirected cytokine-induced killer lymphocytes treatment in GIST, notably ``CSPG4-high'' tumors, and calls for preclinical validation, drug testing in vivo, then in clinical trials. The treatment of gastrointestinal stromal tumors (GIST) must be improved through the development of more reliable prognostic factors and of therapies able to overcome imatinib resistance. The immune system represents an attractive tool. CSPG4, a cell surface proteoglycan, emerged as a potential therapeutic target for immune therapy in different cancers, including cell therapy based on CSPG4-specific chimeric antigen receptor (CAR)-redirected cytokine-induced killer lymphocytes (CSPG4-CAR.CIKs) in sarcomas. CSPG4 expression has never been studied in GIST. We analyzed CSPG4 mRNA expression data of 309 clinical GIST samples profiled using DNA microarrays and searched for correlations with clinicopathological and immune features. CSPG4 expression, higher in tumors than normal digestive tissues, was heterogeneous across tumors. High expression was associated with AFIP low-risk, gastric site, and localized stage, and independently with longer postoperative disease-free survival (DFS) in localized stage. The correlations between CSPG4 expression and immune signatures highlighted a higher anti-tumor immune response in ``CSPG4-high'' tumors, relying on both the adaptive and innate immune system, in which the boost of NK cells by CSPG4-CAR.CIKs might be instrumental, eventually combined with immune checkpoint inhibitors. In conclusion, high CSPG4 expression in GIST is associated with better DFS and offers an immune environment favorable to a vulnerability to CAR.CIKs