Menée aux Pays-Bas à partir de données portant sur 115 et 4 605 patients atteints d'un cancer du tube digestif supérieur, cette étude analyse, par rapport à une

Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice

Markar, Sheraz R. ; Ni, Melody ; Gisbertz, Suzanne S. ; van der Werf, Leonie ; Straatman, Jennifer ; van der Peet, Donald ; Cuesta, Miguel A. ; Hanna, George B. ; van Berge Henegouwen, Mark I.

PURPOSET : he aim of this study was to examine the external validity of the randomized TIME trial, when minimally invasive esophagectomy (MIE) was implemented nationally in the Netherlands, using data from the Dutch Upper GI Cancer Audit (DUCA) for transthoracic esophagectomy. METHODS : Original patient data from the TIME trial were extracted along with data from the DUCA dataset (2011-2017). Multivariate analysis, with adjustment for patient factors, tumor factors, and year of surgery, was [...]

Menée au Japon à partir de données portant sur 121 patientes atteintes d'un cancer du col de l'utérus de stade précoce ou de stade localement avancé (durée médiane de suivi : 42 ans), cette étude évalue, du point de vue du taux de contrôle local de la maladie et du taux de survie globale à 5 ans, l'efficacité d'une méthode d'hystérectomie radicale avec résection étendue du tissu paracervical

Oncological Outcomes After Okabayashi-Kobayashi Radical Hysterectomy for Early and Locally Advanced Cervical Cancer

Sakuragi, Noriaki ; Kato, Tatsuya ; Shimada, Chisa ; Kaneuchi, Masanori ; Todo, Yukiharu ; Mitamura, Takashi ; Takeda, Mahito ; Kudo, Masataka ; Murakami, Gen ; Watari, Hidemichi

Importance : The role of surgery in early-stage cervical cancer has been established, but it is controversial in locally advanced cervical cancer. Objective : To determine whether a radical hysterectomy method with extended removal of paracervical tissue for locally advanced cervical cancer is associated with satisfactory oncological outcomes. Design, Setting, and Participants : This retrospective cohort study was conducted from January 1, 2002, to December 31, 2011, and participants were [...]

Menée à l'aide de lignées cellulaires et à partir d'échantillons plasmatiques issus de patients atteints d'une leucémie lymphoïde chronique, cette étude met en évidence le rôle de la glucuronosyltransférase UGT2B17 dans la réponse thérapeutique

UGT2B17 modifies drug response in chronic lymphocytic leukaemia

Allain, Éric P. ; Rouleau, Michèle ; Vanura, Katrina ; Tremblay, Sophie ; Vaillancourt, Joanie ; Bat, Vincent ; Caron, Patrick ; Villeneuve, Lyne ; Labriet, Adrien ; Turcotte, Véronique ; Le, Trang ; Shehata, Medhat ; Schnabl, Susanne ; Demirtas, Dita ; Hubmann, Rainer ; Joly-Beauparlant, Charles ; Droit, Arnaud ; Jäger, Ulrich ; Staber, Philipp B. ; Levesque, Eric ; Guillemette, Chantal

Background : High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents. Methods : Functional enzymatic assays and patients’ plasma samples were analysed by mass-spectrometry to evaluate [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence l'intérêt de lymphocytes CAR-T anti-CD117 pour éliminer les cellules hématopoïétiques saines et cancéreuses exprimant l'antigène CD117

Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells

Myburgh, Renier ; Kiefer, Jonathan D. ; Russkamp, Norman F. ; Magnani, Chiara F. ; Nuñez, Nicolás ; Simonis, Alexander ; Pfister, Surema ; Wilk, C. Matthias ; McHugh, Donal ; Friemel, Juliane ; Müller, Antonia M. ; Becher, Burkhard ; Münz, Christian ; van den Broek, Maries ; Neri, Dario ; Manz, Markus G.

Acute myeloid leukemia (AML) initiating and sustaining cells maintain high cell-surface similarity with their cells-of-origin, i.e., hematopoietic stem and progenitor cells (HSPCs), and identification of truly distinguishing leukemia-private antigens has remained elusive to date. To nonetheless utilize surface antigen-directed immunotherapy in AML, we here propose targeting both, healthy and malignant human HSPC, by chimeric antigen receptor (CAR) T-cells with specificity against CD117, the [...]

Menée à l'aide de lignées cellulaires de tumeurs germinales et d'échantillons tumoraux issus de patients pédiatriques et de patients adultes, cette étude met en évidence des mécanismes par lesquels l'inhibition des kinases CDK4/6 induit l'arrêt du cycle cellulaire et l'apoptose des cellules cancéreuses

CDK4/6 inhibition presents as a therapeutic option for paediatric and adult germ cell tumours and induces cell cycle arrest and apoptosis via canonical and non-canonical mechanisms

Skowron, Margaretha A. ; Vermeulen, Marieke ; Winkelhausen, Anna ; Becker, Teresa K. ; Bremmer, Felix ; Petzsch, Patrick ; Schönberger, Stefan ; Calaminus, Gabriele ; Köhrer, Karl ; Albers, Peter ; Nettersheim, Daniel

Background : Germ cell tumours (GCTs) are the most common solid malignancies in young men. Although high cure rates can be achieved, metastases, resistance to cisplatin-based therapy and late toxicities still represent a lethal threat, arguing for the need of new therapeutic options. In this study, we analysed the potential of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors palbociclib and ribociclib (PaRi) as molecular drugs to treat cisplatin-resistant and -sensitive paediatric and adult [...]

Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence l'intérêt de la luméfrantine, un antipaludique, pour lever la résistance des glioblastomes au témozolomide et aux rayonnements ionisants

Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma

Rajesh, Yetirajam ; Biswas, Angana ; Kumar, Utkarsh ; Banerjee, Indranil ; Das, Subhayan ; Maji, Santanu ; Das, Swadesh K. ; Emdad, Luni ; Cavenee, Webster K. ; Mandal, Mahitosh ; Fisher, Paul B.

No current therapies prevent recurrence in patients with glioblastoma multiforme (GBM). Extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT) are important processes regulating GBM progression and acquisition of radiation and temozolomide (radio/TMZ) resistance. Fli-1 choreographs ECM remodeling and EMT in GBM via transcriptional regulation of HSPB1. Lumefantrine, an antimalarial drug, inhibits the transcriptional activities of Fli-1 and its downstream targets HSPB1, [...]

Menée au Japon à partir de données portant sur 361 patients pédiatriques atteints d’un hépatoblastome, cette étude évalue l’efficacité, du point de vue de la survie sans événement et de la survie globale à 5 ans, et la toxicité de plusieurs stratégies thérapeutiques à base d’une chimiothérapie combinant cisplatine, tétrahydropyranyle et adriamycine

Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol

Eiso Hiyama, Tomoro Hishiki, Kenichiro Watanabe (et al.)

PURPOSE : We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS : From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) [...]

Menée à partir de données portant sur 96 patients atteints d’un cancer de stade avancé ou non résécable, cette étude rétrospective identifie les symptômes associés à une utilisation d’inhibiteurs de TRK et analyse la sévérité et la durée de ces symptômes

Characterization of On-Target Adverse Events Caused by TRK Inhibitor Therapy

D.Liu, J.Flory, A. Lin, J.Falcon (et al.)

Purpose : The TRK pathway controls appetite, balance, and pain sensitivity. While these functions are reflected in the on-target adverse effects (AEs) observed with TRK inhibition, these AEs remain under-recognized, and pain upon drug withdrawal has not previously been reported. As TRK inhibitors are approved by multiple regulatory agencies for TRK or ROS1 fusion-positive cancers, characterizing these AEs and corresponding management strategies is crucial. Methods : Patients with advanced or [...]

A partir d’une revue systématique de la littérature (14 études, 939 patients), cette méta-analyse évalue l’efficacité, du point de vue du taux de réponse globale, du taux de contrôle de la maladie, de la survie globale et de la survie sans progression, des inhibiteurs de points de contrôle immunitaire chez des patients atteints d’un cancer de stade avancé avec haute instabilité des microsatellites

Outcomes Following Immune Checkpoint Inhibitor Treatment of Patients With Microsatellite Instability-High Cancers: A Systematic Review and Meta-analysis

Fausto Petrelli, Michele Ghidini, Antonio Ghidini (et al.)

Importance : The mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors [...]

Menée à partir de données portant sur 735 patients pédiatriques atteints d’un cancer (âge moyen : 8,9 ans), cette étude analyse les facteurs associés au risque de vomissements induits par une chimiothérapie moyennement ou hautement émétisante

Factors Associated With Chemotherapy-Induced Vomiting Control in Pediatric Patients Receiving Moderately or Highly Emetogenic Chemotherapy: A Pooled Analysis

L. Lee Dupuis, George A. Tomlinson, Annpey Pong (et al.)

PURPOSE : To identify factors associated with chemotherapy-induced vomiting (CIV) control in pediatric patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). MATERIALS AND METHODS : An individual, patient?level, pooled analysis was performed using data from five clinical trials of aprepitant or fosaprepitant in pediatric patients receiving HEC or MEC. The proportion of individuals who experienced no vomiting (complete CIV control) during the phase [...]

Mené sur 38 patients pédiatriques (âge : 1-21 ans) atteints d’une leucémie myéloïde aiguë récidivante, cet essai de phase I/II évalue la dose maximale tolérée et l’efficacité, du point de vue du taux de réponse, d’une préparation liposomale (CPX-351) combinant daunorubicine et cytarabine

Phase I/II Study of CPX-351 Followed by Fludarabine, Cytarabine, and Granulocyte-Colony Stimulating Factor for Children With Relapsed Acute Myeloid Leukemia: A Report From the Children’s Oncology Group

Todd M. Cooper, Michael J. Absalon, Todd A. Alonzo (et al.)

PURPOSE : Effective regimens are needed for children with relapsed acute myeloid leukemia (AML). AAML1421 is a phase I/II study of CPX-351, a liposomal preparation of daunorubicin and cytarabine. AAML1421 sought to determine the recommended phase II dose (RP2D) of CPX-351 and the response rate after up to 2 cycles of therapy. PATIENTS AND METHODS : Children > 1 and ? 21 years of age with relapsed/refractory AML were eligible for dose finding; those in first relapse were eligible for the [...]

Menée aux Etats-Unis à partir de données portant sur 298 patients atteints d’un lymphome à grandes cellules B réfractaire ou récidivant, cette étude rétrospective évalue l’efficacité, du point de vue de la mortalité sans récidive, du taux de réponse complète, de la survie sans progression et de la survie globale, et la toxicité de l’axicabtagene ciloleucel, une immunothérapie à base de lymphocytes CAR-T ciblant CD19

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium

Loretta J. Nastoupil, Michael D. Jain, Lei Feng (et al.)

PURPOSE : Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. PATIENTS AND METHODS : Data were collected [...]

Mené en Chine sur 457 patients atteints d’un carcinome épidermoïde de l’œsophage de stade avancé ou métastatique, cet essai de phase III compare l’efficacité, du point de vue de la survie globale, et la toxicité du camrélizumab et d’une chimiothérapie choisie par le médecin (docétaxel ou irinotécan) en traitement de deuxième ligne (durée médiane de suivi : 8,3 mois)

Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study

Prof Jing Huang, Prof Jianming Xu, Yun Chen (et al.)

Background :Patients with advanced or metastatic oesophageal squamous cell carcinoma have poor prognosis and few treatment options after first-line therapy. We aimed to assess efficacy and safety of the anti-PD-1 antibody camrelizumab versus investigator's choice of chemotherapy in previously treated patients. Methods : ESCORT is a randomised, open-label, phase 3 study of patients aged 18 to 75 years with a histological or cytological diagnosis of advanced or metastatic oesophageal squamous [...]

Mené sur 35 patientes atteintes d’un cancer de l’ovaire récidivant, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse globale, et la toxicité d’un traitement combinant olaparib et durvalumab, après l’échec de plusieurs lignes de traitements (nombre médian de thérapies précédentes : 4)

Combination of PARP inhibitor olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: a proof-of-concept phase 2 study

Erika J Lampert, Alexandra S Zimmer, Michelle R Padget (et al.)

Purpose: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase 2 trial of PARPi olaparib and anti-PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis. Experimental Design: In a single-center, proof-of-concept phase 2 study, we enrolled women aged ?18 with recurrent ovarian cancer. All patients were immune-checkpoint [...]

Mené sur 64 patients atteints d’un cancer du pancréas, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse histopathologique, et la toxicité de l’ajout de hautes doses d’hydroxychloroquine à un traitement combinant gemcitabine et nab-paclitaxel

A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients

Herbert J. Zeh, Nathan Bahary, Brian A. Boone, Aatur D. Singhi (et al.)

Purpose: We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel. Patients and Methods: Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed [...]

A partir d’une revue systématique de la littérature publiée entre 2010 et 2020, cette étude analyse, dans un contexte de vie réelle, l’efficacité et la toxicité des inhibiteurs de points de contrôle immunitaire chez des patients atteints d’un cancer du poumon, et souligne l’importance des enjeux liés à l’évaluation de l’utilisation de ces inhibiteurs chez des populations spécifiques (patients âgés, patients infectés par le VIH, patients atteints d’une hépatite, etc.)

Real world data in the era of Immune Checkpoint Inhibitors (ICIs): increasing evidence and future applications in lung cancer

Giulia Pasello, Alberto Pavan, Ilaria Attili (et al.)

Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) quickly subverted the standard of treatment in Non-Small Cell Lung Cancer (NSCLC), where they were first introduced in all comers previously treated advanced/metastatic NSCLC patients and subsequently in the first line of PD-L1 selected cases of metastatic and locally advanced disease. Treatment algorithm is an evolving landscape, where the introduction of front-line ICIs, with or without [...]

Menée aux Pays-Bas dans un contexte de vie réelle à partir de données portant sur 792 patients atteints d’un cancer du poumon à petites cellules de stade étendu diagnostiqué entre 2008 et 2014, cette étude rétrospective analyse l’utilisation de plusieurs stratégies thérapeutiques et la survie associée

Real-world treatment patterns and outcomes of patients with extensive disease small cell lung cancer

Christine M. Cramer?van der Welle, Franz M. N. H. Schramel, Arvid S. van Leeuwen (et al.)

Objective : Clinical outcome data on patients with extensive disease small cell lung cancer (ED SCLC) treated in routine practice is limited. The aim of this retrospective study is to present data on treatment patterns and survival in an unselected patient population with ED SCLC. Methods : All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were included. We collected data on patient characteristics, systemic treatments, overall [...]

Mené sur 80 patients âgés ou fragiles (âge médian : 80 ans) atteints d’un cancer du poumon non à petites cellules EGFR+, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité de faibles doses d’erlotinib

Low-Dose Erlotinib Treatment in Elderly or Frail Patients With EGFR Mutation–Positive Non–Small Cell Lung Cancer: A Multicenter Phase 2 Trial

Shingo Miyamoto, Koichi Azuma, Hidenobu Ishii (et al.)

Importance : Although the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for EGFR gene mutation–positive non–small cell lung cancer is well established, optimal dosing remains to be established, especially in elderly or frail patients. Objective : To investigate the efficacy and safety of low-dose erlotinib in elderly or frail patients with EGFR mutation–positive non–small cell lung cancer. Design, Setting, and Participants : Single-arm phase 2 trial with the Southwest [...]

Mené au Japon sur 804 patients atteints d’un cancer du poumon non épidermoïde non à petites cellules de stade II à IIIA et ayant été totalement réséqué, cet essai de phase III compare l’efficacité, du point de vue de la survie sans récidive, et la toxicité du pémétrexed et de la vinorelbine, dispensés en combinaison avec du cisplatine en traitement adjuvant (durée médiane de suivi : 45,2 mois)

Randomized Phase III Study of Pemetrexed Plus Cisplatin Versus Vinorelbine Plus Cisplatin for Completely Resected Stage II to IIIA Nonsquamous Non–Small-Cell Lung Cancer

Hirotsugu Kenmotsu, Nobuyuki Yamamoto, Takeharu Yamanaka (et al.)

PURPOSE : To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS : We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive [...]

A partie d’une revue de la littérature, cette étude analyse les enjeux liés au développement de l’utilisation des inhibiteurs de points de contrôle immunitaire chez les patients atteints d’un cancer colorectal

Revolutionizing the Landscape of Colorectal Cancer Treatment: The Potential Role of Immune Checkpoint Inhibitors

Mai F. Tolba

Colorectal cancer (CRC) represents the third cause of cancer?related mortalities worldwide. The progression of CRC to the metastatic phase significantly compromises the overall survival rates. Despite the advances in the therapeutic protocols, CRC treatment is still challenging. Cancer immunotherapy joined the ranks of surgery, chemotherapy, radiotherapy and targeted therapy as the fifth pillar in the foundation of cancer therapeutics. Interruption of the immunosuppressive signals within the [...]

Mené sur 287 patients atteints d’un sarcome des tissus mous à haut risque de récidive, cet essai de phase III compare l’efficacité, du point de vue de la survie sans maladie et de la survie globale, de plusieurs protocoles de chimiothérapies néoadjuvantes adaptées selon l’histologie de la tumeur et d’une chimiothérapie néoadjuvante standard (anthracycline et ifosfamide)

Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups

Alessandro Gronchi, Emanuela Palmerini, Vittorio Quagliuolo (et al.)

PURPOSE : To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall. PATIENTS AND METHODS : This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, ? 5 cm) of an extremity or trunk wall, belonging to one of the following five [...]

Mené sur 284 et 287 patientes atteintes d’un cancer du sein HR+ de stade avancé, cet essai de phase III évalue le délai avant la survenue d'événements indésirables liés à un traitement combinant alpélisib et fulvestrant et analyse les modalités de prise en charge de ces toxicités

Time Course and Management of Key Adverse Events During the Randomized Phase 3 SOLAR-1 Study of PI3K Inhibitor Alpelisib Plus Fulvestrant in Patients With HR-Positive Advanced Breast Cancer

H.S.Rugo, F.André, T.Yamashita, H.Cerda (et al.)

Background : Alpelisib (?-selective PI3K inhibitor) plus fulvestrant is approved in multiple countries for men and post-menopausal women with PIK3CA-mutated, hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer following progression on or after endocrine therapy. A detailed understanding of alpelisib’s safety profile should inform adverse event (AE) management and enhance patient care. Patients and methods : AEs in the phase 3 SOLAR-1 [...]

A partir d’une revue systématique de la littérature (6 études, 3 421 patientes), cette méta-analyse évalue l’efficacité, du point de vue de la survie globale, des inhibiteurs anti-CDK4/6 chez des patientes atteintes d’un cancer du sein de stade métastatique, selon certaines spécificités (sous-type moléculaire de la tumeur, statut ménopausique, nombre de lignes de traitements, etc.)

Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis

Francesco Schettini, Fabiola Giudici, Mario Giuliano (et al.)

Background : CDK4/6-inhibitors (CDK4/6i)+endocrine therapy (ET) prolonged progression-free survival as first/second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC) prognosis. Given the recent publication of overall survival (OS) data for the three CDK4/6i, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods : We conducted a systematic literature search to select [...]

Menée à partir de données portant sur 102 patients atteints d’un glioblastome récemment diagnostiqué, cette étude rétrospective évalue l’efficacité, du point de vue de la survie globale, et la toxicité de l’ajout du valganciclovir (un médicament antiviral) à une thérapie standard

Valganciclovir as add-on to standard therapy in glioblastoma patients

Giuseppe Stragliotto, Mattia Russel Pantalone, Afsar Rahbar (et al.)

Purpose: Several groups have reported a prevalence of human cytomegalovirus (CMV) in glioblastoma close to 100%. Previously, we reported that treatment with the antiviral drug valganciclovir as an add-on to standard therapy significantly prolonged survival in 50 glioblastoma patients. Here we present an updated retrospective analysis that includes an additional 52 patients. Experimental Design: From December 2006 to November 2019, 102 patients with newly diagnosed glioblastoma received [...]

Menée par questionnaire auprès de 469 patients atteints d’un carcinome épidermoïde de la tête et du cou de stade métastatique et/ou récidivant, cette étude évalue l’intérêt, du point de vue de la qualité de vie auto-déclarée, du pembrolizumab après l’échec de traitements à base de sels de platine

Quality of Life With Pembrolizumab for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040

Kevin J Harrington, Denis Soulières, Christophe Le Tourneau, Jose Dinis (et al.)

Background : Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab versus standard of care (SOC) in patients with recurrent/metastatic (R/M) HNSCC whose disease recurred/progressed after platinum-containing regimen. Methods : Patients received pembrolizumab 200?mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European [...]

Mené sur 20 patients atteints d'un mélanome de stade avancé, cet essai de phase I évalue la sécurité d'un traitement combinant nivolumab, ipilimumab et radiothérapie

A Prospective, Phase 1 Trial of Nivolumab, Ipilimumab, and Radiotherapy in Patients with Advanced Melanoma

Postow, Michael A. ; Knox, Susan J. ; Goldman, Debra A. ; Elhanati, Yuval ; Mavinkurve, Vikram ; Wong, Phillip ; Halpenny, Darragh ; Reddy, Sunil K. ; Vado, Kenya ; McCabe, Danielle ; Ramirez, Kristen Aufiero ; Macri, Mary ; Schwarzenberger, Paul ; Ricciardi, Toni ; Ryan, Aileen ; Venhaus, Ralph ; Momtaz, Parisa ; Shoushtari, Alexander N. ; Callahan, Margaret K. ; Chapman, Paul B. ; Wolchok, Jedd D. ; Subrahmanyam, Priyanka B. ; Maecker, Holden T. ; Panageas, Katherine S. ; Barker, Christopher A.

Purpose: Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab. Experimental Design: We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis [...]

A partir d'une revue systématique de la littérature (9 essais incluant au total 5 381 patients), cette méta-analyse évalue l'intérêt d'ajouter un traitement anti-androgénique ou une curiethérapie de type "boost" à une radiothérapie externe pour améliorer la survie globale chez les patients atteints d'un cancer de la prostate de stade localisé

Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials

Jackson, William C. ; Hartman, Holly E. ; Dess, Robert T. ; Birer, Sam R. ; Soni, Payal D. ; Hearn, Jason W. D. ; Reichert, Zachary R. ; Kishan, Amar U. ; Mahal, Brandon A. ; Zumsteg, Zachary S. ; Efstathiou, Jason A. ; Kaffenberger, Samuel ; Morgan, Todd M. ; Mehra, Rohit ; Showalter, Timothy N. ; Krauss, Daniel A. ; Nguyen, Paul L. ; Schipper, Matthew J. ; Feng, Felix Y. ; Sandler, Howard M. ; Hoskin, Peter J. ; Roach, Mack ; Spratt, Daniel E.

PURPOSE : In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS : A [...]

Cet article analyse les interactions entre les microbes et les médicaments, décrit les modifications du microbiote intestinal induites par les médicaments (autres que les antibiotiques) couramment utilisés ainsi que les conséquences cliniques potentielles de ces derniers, puis explique la façon dont le microbiome affecte l'efficacité des médicaments et son rôle dans l'immunothérapie

Interaction between drugs and the gut microbiome

Weersma, Rinse K. ; Zhernakova, Alexandra ; Fu, Jingyuan

The human gut microbiome is a complex ecosystem that can mediate the interaction of the human host with their environment. The interaction between gut microbes and commonly used non-antibiotic drugs is complex and bidirectional: gut microbiome composition can be influenced by drugs, but, vice versa, the gut microbiome can also influence an individual’s response to a drug by enzymatically transforming the drug’s structure and altering its bioavailability, bioactivity or toxicity [...]

Menée à partir de simulations, cette étude évalue la performance de modèles d'essais de phase I du point de vue de la réduction du délai entre l'ouverture de l'essai et la détermination de la dose maximale tolérée, du nombre de patients traités pour déterminer cette dose et de l'association entre le design de l'essai et la dose maximale tolérée identifiée

Model of a Queuing Approach for Patient Accrual in Phase 1 Oncology Studies

Frankel, Paul H. ; Chung, Vincent ; Tuscano, Joseph ; Siddiqi, Tanya ; Sampath, Sagus ; Longmate, Jeffrey ; Groshen, Susan ; Newman, Edward M.

Importance : Phase 1 cancer studies, which guide dose selection for subsequent studies, are almost 3 times more prevalent than phase 3 studies and have a median study duration considerably longer than 2 years, which constitutes a major component of drug development time. Objective : To discern a method to reduce the duration of phase 1 studies in adult and pediatric cancer studies without violating risk limits by better accommodating the accrual and evaluation process (or queue). Design : The [...]

Cet article présente les conclusions d'un atelier de travail américain sur l'utilisation clinique des programmes informatiques dans le diagnostic et le traitement des cancers en médecine de précision

Clinical Application of Computational Methods in Precision Oncology: A Review

Panagiotou, Orestis A. ; Högg, Lori Hoffman ; Hricak, Hedvig ; Khleif, Samir N. ; Levy, Mia A. ; Magnus, David ; Murphy, Martin J. ; Patel, Bakul ; Winn, Robert A. ; Nass, Sharyl J. ; Gatsonis, Constantine ; Cogle, Christopher R.

Importance : There is an enormous and growing amount of data available from individual cancer cases, which makes the work of clinical oncologists more demanding. This data challenge has attracted engineers to create software that aims to improve cancer diagnosis or treatment. However, the move to use computers in the oncology clinic for diagnosis or treatment has led to instances of premature or inappropriate use of computational predictive systems. Objective : To evaluate best practices for [...]

Cet article passe en revue les études cliniques concernant l'arrêt des traitements par inhibiteurs de tyrosine kinase chez les patients atteints d'une leucémie myéloïde chronique en phase de rémission

Treatment-free remission in patients with chronic myeloid leukaemia

Ross, David M. ; Hughes, Timothy P.

In the past few years, international treatment guidelines for chronic myeloid leukaemia have incorporated recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of a treatment-free remission (TFR). Physicians involved in the treatment of chronic myeloid leukaemia need to be sufficiently well informed to guide patients through decision-making about the discontinuation of treatment with TKIs [...]

Cet article analyse les données mettant en évidence une corrélation entre la présence d'ascites et le développement de métastases ainsi que la chimiorésistance dans les cancers ovariens

The untapped potential of ascites in ovarian cancer research and treatment

Ford, Caroline Elizabeth ; Werner, Bonnita ; Hacker, Neville Frederick ; Warton, Kristina

The build-up of fluid in the peritoneal cavity—ascites—is a hallmark of ovarian cancer, the most lethal of all gynaecological malignancies. This remarkable fluid, which contains a variety of cellular and acellular components, is known to contribute to patient morbidity and mortality by facilitating metastasis and contributing to chemoresistance, but remains largely under-researched. In this review, we will critically analyse the evidence associating ascites with metastasis and chemoresistance [...]

Cet article passe en revue les différentes approches destinées à modifier le micro-environnement tumoral pour traiter un adénocarcinome canalaire métastatique du pancréas, analyse les résultats contradictoires observés entre les études précliniques et cliniques puis identifie les stratégies thérapeutiques multimodales en cours d'investigation

The tumour microenvironment in pancreatic cancer — clinical challenges and opportunities

Ho, Won Jin ; Jaffee, Elizabeth M. ; Zheng, Lei

Metastatic pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid tumours despite the use of multi-agent conventional chemotherapy regimens. Such poor outcomes have fuelled ongoing efforts to exploit the tumour microenvironment (TME) for therapy, but strategies aimed at deconstructing the surrounding desmoplastic stroma and targeting the immunosuppressive pathways have largely failed. In fact, evidence has now shown that the stroma is multi-faceted, which illustrates the [...]