Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced non–small cell lung cancer (NSCLC). However, most pivotal phase III trials systematically excluded patients with active brain metastases, precluding the generalization of the results. Although theoretically restricted from crossing the blood–brain barrier, the novel pharmacokinetic/pharmacodynamic profiles of anti-PD-1/PD-L1 drugs have prompted studies to evaluate their activity in patients with NSCLC with active central...
Fri Aug 14, 2020 10:05
Purpose: Low-dose CT screening can reduce lung cancer–related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation–based detection of non–small cell lung cancer (NSCLC). Experimental Design: This nested case–control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer...
Fri Aug 14, 2020 10:05
The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat (1). Patients with cancer are one of the most vulnerable populations. During this pandemic, clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine, and decrease required data collection. Going forward, the oncology research community must use...
Fri Aug 14, 2020 10:05
Purpose: The impact of tertiary lymphoid structures (TLS) in hepatocellular carcinoma (HCC) progression is being extensively investigated. However, their presence during the early steps of human liver carcinogenesis remains unknown. We thus aimed to determine whether TLS are induced in preneoplastic/early hepatic lesions (EHL), and whether they are associated with a particular immune profile. Experimental Design: A series of 127 EHLs (low/high-grade dysplastic nodules, early HCC, and small...
Fri Aug 14, 2020 10:05
The potential immune intersection between COVID-19 disease and cancer therapy raises important practical clinical questions and highlights multiple scientific gaps to be filled. Among available therapeutic approaches to be considered, immune checkpoint inhibitors (ICI) seem to require major attention as they may act at the crossroads between cancer treatment and COVID-19 disease, due to their profound immunomodulatory activity. On the basis of available literature evidence, we suggest guidance to...
Fri Aug 14, 2020 10:05
Purpose: PARP inhibitors (PARPi) are standard-of-care therapy for high-grade serous ovarian cancer (HGSOC). We investigated combining cediranib (antiangiogenic) with olaparib (PARPi) at emergence of PARPi resistance. Patients and Methods: The proof-of-concept EVOLVE study (NCT02681237) assessed cediranib–olaparib combination therapy after progression on a PARPi. Women with HGSOC and radiographic evidence of disease progression were enrolled into one of three cohorts: platinum sensitive after...
Fri Aug 14, 2020 10:05
Purpose: Differentiation syndrome (DS) is a serious adverse reaction of isocitrate dehydrogenase (IDH) inhibitors ivosidenib and enasidenib in patients with (IDH)1- and IDH2-mutated acute myeloid leukemia (AML), respectively. Experimental Design: During FDA review of marketing applications for ivosidenib and enasidenib, data from pivotal trials were queried to identify cases of DS in patients with relapsed or refractory (R/R) AML. One hundred seventy-nine patients with R/R AML received ivosidenib...
Fri Aug 14, 2020 10:05
Purpose: Mantle-cell lymphoma (MCL) is an incurable mature B-cell neoplasm with high initial response rates followed almost invariably by relapse. Prognosis for patients following relapse is poor, and treatment choices are limited. We evaluated the efficacy and safety of zanubrutinib, an investigational selective Bruton's tyrosine kinase (BTK) inhibitor. Patients and Methods: Patients with relapsed/refractory MCL were enrolled in this ongoing phase II, single-arm, open-label study, and treated...
Fri Aug 14, 2020 10:05
Purpose: To identify a predictive biomarker of sorafenib for hepatocellular carcinoma personalized therapy. Experimental Design: The patients treated with or without sorafenib after hepatocellular carcinoma recurrence from multicenters were matched with propensity score matching analysis. The expression levels of Fms-like tyrosine kinase 3 (FLT3) in hepatocellular carcinoma specimens of the matched patients (n = 276) were analyzed by IHC. The optimal cut-off point of FLT3 levels for overall...
Fri Aug 14, 2020 10:05
Purpose: NC-6300 is a novel nanoparticle formulation of epirubicin that has a pH-sensitive linker conjugated to epirubicin. It exhibits selective tumor accumulation owing to enhanced permeability and retention effect. We conducted a phase 1b trial to determine MTD and recommended phase II dose (RP2D) of NC-6300 monotherapy in advanced, metastatic, or unresectable solid tumors, including soft-tissue sarcomas. Patients and Methods: This phase 1b dose-escalation trial of NC-6300 monotherapy...
Fri Aug 14, 2020 10:05
Purpose: Although high T-cell density is a well-established favorable prognostic factor in colorectal cancer, the prognostic significance of tumor-associated plasma cells, neutrophils, and eosinophils is less well-defined. Experimental Design: We computationally processed digital images of hematoxylin and eosin (H&E)–stained sections to identify lymphocytes, plasma cells, neutrophils, and eosinophils in tumor intraepithelial and stromal areas of 934 colorectal cancers in two prospective...
Fri Aug 14, 2020 10:05
Purpose: In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41. Patients and Methods: Eligible patients had a baseline preadjuvant treatment core biopsy sample,...
Fri Aug 14, 2020 10:05
Purpose: Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment. Experimental Design: To study AXL signaling in the context of treatment-resistant...
Fri Aug 14, 2020 10:05
Purpose: Fulvestrant, the first-in-class selective estrogen receptor (ER) degrader (SERD), is clinically effective in patients with ER+ breast cancer, but it has administration and pharmacokinetic limitations. Pharmacodynamic data suggest complete ER degradation is not achieved at fulvestrant's clinically feasible dose. This presurgical study (NCT03236974) compared the pharmacodynamic effects of fulvestrant with AZD9496, a novel, orally bioavailable, nonsteroidal, potent SERD, in treatment-naïve...
Fri Aug 14, 2020 10:05
Purpose: Gliomas are brain tumors with dismal prognoses. The standard-of-care treatments for gliomas include surgical resection, radiation, and temozolomide administration; however, they have been ineffective in providing significant increases in median survival. Antigen-specific cancer vaccines and immune checkpoint blockade may provide promising immunotherapeutic approaches for gliomas. Experimental Design: We have developed immunotherapy delivery vehicles based on synthetic high-density...
Fri Aug 14, 2020 10:05
Purpose: In contrast to the predominant chronic UV exposure–induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China. Patients and Methods: This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab...
Fri Aug 14, 2020 10:05
CD8+ T-cell-Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas
Purpose: Cancer immunoediting shapes tumor progression by the selection of tumor cell variants that can evade immune recognition. Given the immune evasion and intratumor heterogeneity characteristic of gliomas, we hypothesized that CD8+ T cells mediate immunoediting in these tumors. Experimental Design: We developed retrovirus-induced PDGF+Pten–/– murine gliomas and evaluated glioma progression and tumor immunogenicity in the absence of CD8+ T cells by depleting this immune cell population....
Fri Aug 14, 2020 10:05
Purpose: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti–PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC. Patients and Methods: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible...
Fri Aug 14, 2020 10:05
Purpose: We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months. Experimental Design: 112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging...
Fri Aug 14, 2020 10:05
Purpose: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinums and poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. Experimental Design: We performed a 7-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which 9 were gBRCA-mutated....
Fri Aug 14, 2020 18:13
The tumor suppressor p53 exerts pivotal roles in hematopoietic stem cell (HSC) homeostasis. Mutations of the TP53 gene have recently been described in individuals with clonal hematopoieis conferring substantial risk of developing blood cancers. In patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), TP53 aberrations - mutations, deletions and a combination thereof - are encountered at a constant frequency of approximately 10%. These aberrations affect HSCs transforming...
Fri Aug 14, 2020 18:13
PrOTYPE is a locked down assay validated to Institute of Medicine standards, using NanoString technology to classify High Grade Serous Ovarian Cancer into four subgroups. Future directions will include prospective-retrospective analysis and prospective clinical validation to define the predictive role of this assay and its role in influencing treatment decisions.
Fri Aug 14, 2020 18:13
Purpose: Malignant pleural mesothelioma (MPM) is considered an orphan disease with few treatment options. Despite multimodality therapy, the majority of MPM recur and eventually become refractory to any systemic treatment. One potential mechanism underlying therapeutic resistance may be intratumor heterogeneity (ITH), making MPM challenging to eradicate. However, the ITH architecture of MPM and its clinical impact have not been well studied. Experimental design: We delineated the immunogenomic ITH...
Fri Aug 14, 2020 18:13
Purpose: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle maximum-tolerated dose (MTD), and pharmacokinetic profile of romidepsin in this setting. Experimental Design: Patients with select advanced solid tumors or hematologic malignancies...
Fri Aug 14, 2020 18:13
Purpose: Induction cisplatin and gemcitabine chemotherapy is a standard treatment for locally advanced NPC. Inhibition of VEGF axis has been shown to promote maturation of microvasculature and improve perfusion. We conducted a four-arm study to assess the effect of 2 doses of either sunitinib or bevacizumab with chemotherapy in NPC. Experimental Design: Patients with treatment naïve locally advanced NPC were treated with 3 cycles of 3-weekly cisplatin and gemcitabine preceded by 1 week of anti-VEGF...
Fri Aug 14, 2020 18:13
Purpose: To determine if a targeted exome panel utilizing matched normal DNA can accurately detect germline and somatic HLA genes in synovial sarcoma (SS) patients and whether select HLA-A*02 genotypes are prognostic or predictive of outcome in metastatic SS. Experimental Design: Metastatic SS patients consented to HLA typing by a Clinical Laboratory Improvement Amendments (CLIA)-certified test to determine eligibility for a clinical trial of NY-ESO-1-specific engineered T cells restricted to carriers...
Fri Aug 14, 2020 18:13
Purpose: Immune checkpoint blockade has demonstrated clinical benefits across multiple solid tumor types; however, resistance and relapse often occurs. New immunomodulatory targets, which are highly expressed in activated immune cells, are needed. MEDI0562, an agonistic humanized monoclonal antibody (mAb), specifically binds to the costimulatory molecule OX40. This first-in-human study evaluated MEDI0562 in adultswith advanced solid tumors. Experimental Design: In this phase I, multicenter, open-label,...
Fri Aug 14, 2020 18:13
Purpose: T cell recruitment, survival and proliferation are the important limitations to chimeric antigen receptor (CAR) T cells therapy in the treatment of solid tumors. In this study we engineered CAR-T cells to co-express cytokines IL-7 and CCL21 (7x21 CAR-T), a cytokine combination in order to improve proliferation and chemotaxis of CAR-T cells. Experimental design: CLDN18.2 specific second-generation CAR-T cells coexpressing cytokines were prepared using retroviral vector transduction. The proliferation...
Fri Aug 14, 2020 18:13
Publication date: Available online 15 August 2020Source: Critical Reviews in Oncology/HematologyAuthor(s): Nicola Silvestris, Antonella Argentiero, Giordano Domenico Beretta, Paolo Di Bartolo, Monica Montagnani, Romano Danesi, Pietro Ferrari, Stella D’Oronzo, Stefania Gori, Antonio Russo, Silvia Acquati, Marco Gallo
Sun Aug 16, 2020 16:06
Opinion statement Hormone receptor (HR) positive breast cancer has a high propensity for late recurrences that might be prevented with longer durations of endocrine therapy (ET). However, trials evaluating extended adjuvant ET have produced somewhat conflicting results. Additionally, ET is associated with not only day to day side effects that can impact quality of life, but more detrimental effects that can cause significant morbidity. Although patients with higher stage disease...
Sat Aug 15, 2020 03:00
Publication date: Available online 15 August 2020Source: European Journal of CancerAuthor(s): Erik E.L. Jansen, Nadine Zielonke, Andrea Gini, Ahti Anttila, Nereo Segnan, Zoltán Vokó, Urška Ivanuš, Martin McKee, Harry J. de Koning, Inge M.C.M. de Kok
Sun Aug 16, 2020 15:45
Publication date: Available online 15 August 2020Source: European Journal of CancerAuthor(s): Tariq Kewan, Fahrettin Covut, Ramsha Ahmed, Abdo Haddad, Hamed Daw
Sun Aug 16, 2020 15:45
Publication date: Available online 15 August 2020Source: European Journal of CancerAuthor(s): Mikael L. Soucisse, Micheal Flood, Lucas Sideris, Pierre Dubé, Alexander Heriot
Sun Aug 16, 2020 15:45
Publication date: September 2020Source: European Journal of Cancer, Volume 137Author(s): Arndt Stahler, Sebastian Stintzing, Jobst C. von Einem, Christoph B. Westphalen, Kathrin Heinrich, Nicole Krämer, Marlies Michl, Dominik P. Modest, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Tobias Heintges, Christoph Kahl, Frank Kullmann, Werner Scheithauer, Markus Moehler, Florian Kaiser, Thomas Kirchner, Andreas Jung, Volker Heinemann
Sat Aug 15, 2020 19:48
Publication date: September 2020Source: European Journal of Cancer, Volume 137Author(s): Matthieu Frasca, Camille Sabathe, Suzette Delaloge, Angeline Galvin, Anne Patsouris, Christelle Levy, Marie A. Mouret-Reynier, Isabelle Desmoulins, Laurence Vanlemmens, Thomas Bachelot, Anthony Goncalves, Virginie Perotin, Lionel Uwer, Jean S. Frenel, Jean M. Ferrero, Carole Bouleuc, Jean C. Eymard, Véronique Dieras, Marianne Leheurteur, Thierry Petit
Sat Aug 15, 2020 19:48
Publication date: September 2020Source: European Journal of Cancer, Volume 137Author(s): Margot T.M. Reinders, Suzanne van Meer, Mark C. Burgmans, Koert P. de Jong, Heinz-Josef Klümpen, Robert A. de Man, D. (Sandjai) Ramsoekh, Dave Sprengers, Eric T.T.L. Tjwa, Judith de Vos-Geelen, Karel J. van Erpecum, Lydia G.M. van der Geest, Dutch Hepatocellular & Cholangiocarcinoma Group (DHCG)
Fri Aug 14, 2020 16:53
Publication date: September 2020Source: European Journal of Cancer, Volume 137Author(s): Deborah Meyran, Arnaud Petit, Joelle Guilhot, Meinolf Suttorp, Petr Sedlacek, Eveline De Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Srdjana Culic, Barbara de Moerloose, Andrea Biondi, Frédéric Millot
Fri Aug 14, 2020 16:53
Publication date: Available online 15 August 2020Source: European Journal of Surgical OncologyAuthor(s): Wenju Chang, Ye Wei, Li Ren, Guodong He, Tianyu Liu, Meiling Ji, Mi Jian, Yijiao Chen, Fei Liang, Jianmin Xu
Sun Aug 16, 2020 17:11
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