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Spatial transcriptome mapping of the desmoplastic growth pattern of colorectal liver metastases by in situ sequencing reveals a biologically relevant zonation of the desmoplastic rim Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-25 Axel Andersson, Maria Escriva Conde, Olga Surova, Peter Vermeulen, Carolina Wählby, Mats Nilsson, Hanna Nyström
Purpose: We describe the fibrotic rim formed in the desmoplastic growth pattern (DHGP) of colorectal cancer liver metastasis (CLM) using in situ sequencing (ISS). The origin of the desmoplastic rim is still a matter of debate, and the detailed cellular organization has not yet been fully elucidated. Understanding the biology of the DHGP in CLM can explore targeted treatment to improve survival. Experimental
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CDK9 inhibition by dinaciclib is a therapeutic vulnerability in epithelioid hemangioendothelioma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-25 Ajaybabu V. Pobbati, Ashley Burtscher, Nandini Rajaram Siva, Andrea Hallett, Todd Romigh, Kepeng Che, Bin Zhao, Jesse A. Coker, Nancy Wang, Shaun R. Stauffer, Brian P. Rubin
Purpose: There are no effective treatment options for patients with aggressive epithelioid hemangioendothelioma (EHE) driven by the TAZ-CAMTA1 (TC) fusion gene. Here, we aimed to understand the regulation of TC using pharmacological tools and identify vulnerabilities that can potentially be exploited for the treatment of EHE. Experimental Design: TC is a transcriptional co-regulator; we hypothesized
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Biomarker analyses investigating disease biology and associations with outcomes in the JAVELIN Merkel 200 trial of avelumab in metastatic Merkel cell carcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-24 Sandra P. D'Angelo, Céleste Lebbé, Paul Nghiem, Andrew S. Brohl, Thomas Mrowiec, Trent Leslie, Sara Georges, Güelseren Güezel, Parantu Shah
Purpose: Avelumab (anti–PD-L1) became the first approved treatment for metastatic Merkel cell carcinoma (mMCC) based on results from the phase 2 JAVELIN Merkel 200 trial. We report exploratory biomarker analyses from the trial. Patients and methods: Patients with mMCC (n=88) with or without prior first-line chemotherapy received avelumab 10 mg/kg every 2 weeks. Analyses included: somatic mutations
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Platinum-based chemotherapy induces opposing effects on immunotherapy response-related spatial and stromal biomarkers in the bladder cancer microenvironment Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-24 Maksim A. Chelushkin, Jeroen van Dorp, Sandra van Wilpe, Iris M. Seignette, Jan-Jaap J. Mellema, Maartje Alkemade, Alberto Gil-Jimenez, Dennis Peters, Wim Brugman, Chantal F. Stockem, Erik Hooijberg, Annegien Broeks, Bas W.G. van Rhijn, Laura S. Mertens, Antoine G. Van der Heijden, Niven Mehra, Maurits L. van Montfoort, Lodewyk F.A. Wessels, Daniel J. Vis, Michiel S. Van der Heijden
Purpose: Platinum-based chemotherapy and immune checkpoint inhibitors are key components of systemic treatment for muscle-invasive and advanced urothelial cancer. The ideal integration of these two treatment modalities remains unclear as clinical trials have led to inconsistent results. Modulation of the tumor-immune microenvironment by chemotherapy is poorly characterized. We aimed to investigate
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The Difficulty in Defining the True High-Risk Smoldering Myeloma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-24 Niels Weinhold, Leo Rasche
Early intervention trials have been initiated for the precursor disease smoldering myeloma (SMM). A recent study showed that genomic complexity varies widely among treated high-risk SMM patients and is associated with response to triplet therapy, suggesting that established clinical risk scores often fail to discriminate between stable and aggressive disease.
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SJPedPanel: A pan-cancer gene panel for childhood malignancies to enhance cancer monitoring and early detection Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-24 Pandurang Kolekar, Vidya Balagopal, Li Dong, Yanling Liu, Scott Foy, Quang Tran, Heather Mulder, Anna L.W. Huskey, Emily Plyler, Zhikai Liang, Jingqun Ma, Joy Nakitandwe, Jiali Gu, Maria Namwanje, Jamie Maciaszek, Debbie Payne-Turner, Saradhi Mallampati, Lu Wang, John Easton, Jeffery M. Klco, Xiaotu Ma
Purpose: To design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples. Experimental Design: In addition to 5,275 coding exons, SJPedPanel also covers 297 introns for fusions/structural variations and 7,590 polymorphic sites for copy number alterations. Capture uniformity and limit of detection are determined by targeted sequencing of cell
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Translational history and hope of immunotherapy of canine tumors Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-23 Jeffrey N. Bryan, Charles A. Maitz
Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs’ diverse genetic makeup, makes them ideal subjects for studying cancer therapies. Tumors like osteosarcoma (cOSA), hemangiosarcoma (cHSA), soft-tissue sarcoma (cSTS), and non-Hodgkin
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Mutant IDH modulates suppressive myeloid populations in malignant glioma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-23 Eric P. Grewal, Leland G.K. Richardson, Jing Sun, Rishab Ramapriyan, Maria Martinez-Lage, Julie J. Miller, Bob S. Carter, Daniel P. Cahill, William T. Curry, Bryan D. Choi
Purpose: Mutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 have critical diagnostic and prognostic significance in diffuse gliomas. Neomorphic mutant IDH activity has been previously implicated in T-cell suppression; however, the effects of IDH mutations on intratumoral myeloid populations remain underexplored. Here, we investigate the influence of IDH status on the myeloid compartment
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Improving Collection and Analysis of Overall Survival Data Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-22 Lisa R. Rodriguez, Nicole J. Gormley, Ruixiao Lu, Anup K. Amatya, George D. Demetri, Keith T. Flaherty, Ruben A. Mesa, Richard Pazdur, Mikkael A. Sekeres, Minghua Shan, Steven Snapinn, Marc R. Theoret, Rukiya Umoja, Jonathon Vallejo, Nicholas J. H. Warren, Qing Xu, Kenneth C. Anderson
Advances in anticancer therapies have provided crucial benefits for millions of patients who are living long and fulfilling lives. While these successes should be celebrated, there is certainly room to continue improving cancer care. Increased long-term survival presents additional challenges for determining whether new therapies further extend patients’ lives through clinical trials, commonly known
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Update on Genetic Counselor Practice and Recommendations for Pediatric Cancer Predisposition Evaluation and Surveillance Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-22 Kristin Zelley, Jaclyn Schienda, Bailey Gallinger, Wendy K. Kohlmann, Rose B. McGee, Sarah R. Scollon, Kami Wolfe. Schneider
In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop at which international experts in pediatric cancer predisposition met to update the previously published 2017 consensus statements on pediatric cancer predisposition syndromes. Since 2017, advances in tumor and germline genetic testing and increased understanding of cancer predisposition
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Phase II trial of HER-Vaxx, a B cell peptide-based vaccine, in HER2-overexpressing advanced gastric cancer patients under platinum-based chemotherapy (HERIZON) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-19 Joshua Tobias, Marina Maglakelidze, Zoran Andrić, Dinara Ryspayeva, Iurie Bulat, Ivan Nikolić, Zoran Petrovic, Tanuj Chawla, Rajnish Nagarkar, Erika Garner-Spitzer, Christoph C. Zielinski, Leslie Mi Ok. Chong, Bonnie Nixon, Nicholas J. Ede, Sharon Yavrom, Michael Kundi, Ursula Wiedermann
Purpose: A multicenter, randomized, open-label, Phase II study (HERIZON; NCT02795988) was conducted to evaluate the clinical and immunological efficacy of HER-Vaxx (IMU-131), a B-cell, peptide-based vaccine targeting HER2 overexpressed in 6%-30% of gastroesophageal adenocarcinomas (GEAs). Patients and Methods: Patients (n=36) with GEA were treated with standard-of-care chemotherapy (n=17) or HER-Vaxx
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Cryoablation does not significantly contribute to systemic effector immune responses in poorly immunogenic B16F10 melanoma model Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Chakradhar Yakkala, Jesus Corria-Osorio, Lana Kandalaft, Alban Denys, Bhanu Koppolu, Rafael Duran
Purpose: Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Pre-clinical studies employing immunogenic tumor models have shown that cryoablation evokes anti-tumor immune responses. How cryoablation impacts immune responses in poorly immunogenic tumors has not been sufficiently explored.
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Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Yazi Yang, Sen Qin, Mengyu Yang, Ting Wang, Ru Feng, Chunli Zhang, Enrun Zheng, Qinghua Li, Pengyu Xiang, Shangyong Ning, Xiaodong Xu, Xin Zuo, Shuai Zhang, Xiaoya Yun, Xuehong Zhou, Yue Wang, Lin He, Yongfeng Shang, Luyang Sun, Hui Liu
Purpose: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. Experimental Design: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day −4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. Results: Our analysis
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The innate immune landscape of dMMR/MSI cancers predicts outcome of nivolumab treatment: results from the Drug Rediscovery Protocol Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-18 Laurien J. Zeverijn, Birgit S. Geurts, Thomas W. Battaglia, Jade M. van Berge Henegouwen, Gijs F. de Wit, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Paul Roepman, Wendy W.J. de Leng, Anne M.L. Jansen, Myriam Chalabi, Carla M.L. van Herpen, Lot A. Devriese, Frans L.G. Erdkamp, Mariette Labots, Maja J. A. de Jonge, Emile D. Kerver, Adriaan D. Bins, Lindsay V.M. Leek, Jessica C
Purpose: Treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid dMMR/MSI tumors and in-depth biomarker analyses were performed to inform precision immunotherapy approaches. Patients and methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol (DRUP), a pan-cancer clinical trial
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Oral and gut microbiome alterations in oral chronic graft-versus-host disease: results from Close Assessment and Testing for Chronic GVHD (CATCH study) Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Armin Rashidi, Joseph Pidala, Betty K. Hamilton, Steven Z. Pavletic, Katie Kim, Alex Zevin, Jacqueline W. Mays, Stephanie J. Lee
Purpose: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic graft-versus-host disease (cGVHD) pathogenesis is unknown. In addition, while the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown. Experimental
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PIKing up and AKTing on resistance mutations in osimertinib-treated EGFR-mutated NSCLC Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Natalie I. Vokes, Xiuning Le, Timothy A. Yap
A recent study identified high rates of PI3K-AKT pathway mutations from the FLAURA and AURA3 osimertinib trials and pre-clinically validated that these mutations decreased osimertinib sensitivity in EGFR-mutated NSCLC. The AKT inhibitor capivasertib was found to overcome this resistance, providing important rationale for the development of AKT inhibitors in NSCLC.
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Novel Combinations of Immunotherapies or DNA Damage Repair Inhibitors in Platinum-Refractory Extensive-Stage Small-Cell Lung Cancer: The Phase II BALTIC Study Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Niels Reinmuth, Oscar Juan-Vidal, Dariusz Kowalski, Maciej Bryl, Anna Kryzhanivska, David Vicente, Zsolt Horváth, Gabriella Gálffy, Eszter Csánky, Zsolt Pápai Székely, Ihor Vynnychenko, Jon Armstrong, Tapashi Dalvi, Mingchao Xie, Sonia Iyer, Yashaswi Shrestha, Haiyi Jiang, Igor Bondarenko
Purpose: The phase II, multiarm, signal-searching BALTIC study (NCT02937818) assessed novel treatment combinations for platinum-refractory/resistant extensive-stage small-cell lung cancer (ES-SCLC). Experimental Design: Patients with ES-SCLC with progressive disease during or within 90 days of completing first-line platinum-based chemotherapy received one of three regimens: durvalumab plus tremelimumab
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Precision oncology and systemic targeted therapy in Pseudomyxoma Peritonei Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Jordi Martínez-Quintanilla, Débora Cabot, Doménico Sabia, Oriol Arqués, Jordi Vergés, Irene Chicote, Lana Bijelic, Laia Cabellos, Anna M. Alcántara, Isabel Ramos, Pedro Barrios, Oriol Crusellas, Lina M. Palacio, Juan A. Cámara, Jorge Barriuso, Juan J. Jiménez, Pau Muñoz-Torres, Lara Nonell, Raquel Flores, Enzo Médico, Marcello Guaglio, Javier Ros, Elena Élez, Josep Tabernero, Omer Aziz, Marcello Deraco
Purpose: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in PMP patients. New therapeutic strategies are therefore urgently needed for these
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Targeting AKR1B10 by drug repurposing with epalrestat overcomes chemoresistance in non-small cell lung cancer patient-derived tumor organoids Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-17 Kanve N. Suvilesh, Yariswamy Manjunath, Yulia I. Nussbaum, Mohamed Gadelkarim, Murugesan Raju, Akhil Srivastava, Guangfu Li, Wesley C. Warren, Chi-Ren Shyu, Feng Gao, Matthew A. Ciorba, Jonathan B. Mitchem, Satyanarayana Rachagani, Jussuf T. Kaifi
Purpose: Systemic treatments given to non-small cell lung cancer (NSCLC) patients are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTOs) and matched tumor tissues from surgically treated NSCLC patients to identify drug repurposing targets to overcome resistance towards standard-of-care platinum-based doublet chemotherapy. Experimental
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Interim Phase II Results Using Panitumumab-IRDye800CW During Transoral Robotic Surgery in Patients with Oropharyngeal Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-16 Logan D. Stone, Benjamin B. Kasten, Shilpa Rao, Manuel L. Gonzalez, Todd M. Stevens, Diana Lin, William Carroll, Benjamin Greene, Lindsay S. Moore, Andrew Fuson, Sherin James, Yolanda E. Hartman, Susan McCammon, Bharat Panuganti, Lisle M. Nabell, Yufeng Li, Mei Li, Luke Bailey, Eben L. Rosenthal, Harishanker Jeyarajan, Carissa M. Thomas, Jason M. Warram
Purpose: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence guided surgery (FGS) strategies to aid
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Spatial heterogeneity of immune regulators drives dynamic changes of local immune responses, affecting disease outcomes in pancreatic cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Eva Karamitopoulou, Anna Silvia Wenning, Animesh Acharjee, Pauline Aeschbacher, Ilaria Marinoni, Inti Zlobec, Beat Gloor, Aurel Perren
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is considered a low immunogenic tumor with “cold” tumor microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies. Here we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response. Experimental Design: We performed spatial proteomic and transcriptomic analyses and multiplexed immunofluorescence
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NETosis Impact on Tumor Biology, Radiation, and Systemic Therapy Resistance Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Yvonne M. Mowery, Jason J. Luke
NETosis via lytic neutrophil death or neutrophil activation is associated with standard cancer therapies, notably including radiotherapy, is immunosuppressive, and may enhance metastasis and treatment resistance. This emerging area of research should be prioritized in drug development and standard of care treatment paradigms including radiation, chemo- and immunotherapy.
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Associations of immune checkpoint predictive biomarkers MHC-I and MHC-II with clinical and molecular features in a diverse breast cancer cohort Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-15 Xiaopeng Sun, Laura C. Kennedy, Paula I. Gonzalez-Ericsson, Violeta Sanchez, Melinda Sanders, Charles M. Perou, Melissa A. Troester, Justin M. Balko, Sonya A. Reid
Purpose: Immunotherapy (IO) in triple negative breast cancer (TNBC) has improved survival outcomes, with promising improvements in pCR rates among early high-risk HR+/HER2- breast cancers. However, biomarkers are needed to select patients likely to benefit from IO. MHC-I and tumor-specific MHC-II (tsMHC-II) expression are candidate biomarkers for PD-(L)1 checkpoint inhibition, but existing data from
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Circulating tumor DNA dynamics reveal KRAS G12C mutation heterogeneity and response to treatment with the KRAS G12C inhibitor divarasib in solid tumors Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Yoonha Choi, Neekesh V. Dharia, Tomi Jun, Julie Chang, Stephanie Royer-Joo, Kenneth K. Yau, Zoe June. Assaf, Junko Aimi, Smruthy Sivakumar, Meagan Montesion, Adrian Sacher, Patricia LoRusso, Jayesh Desai, Jennifer L. Schutzman, Zhen Shi
Purpose: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study. Experimental design: Plasma samples were collected for serial ctDNA profiling at baseline (Cycle 1
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A Phase II study assessing Long-Term Response to Ibrutinib Monotherapy in recurrent or refractory CNS Lymphoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Christian Grommes, Subhiksha Nandakumar, Lauren R. Schaff, Igor Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Jacqueline Stone, Alissa A. Thomas, Sarah S. Tang, Julia Wolfe, Alexis Bozza, Venissala Wongchai, Allison Hyde, Emma Barrett, Elizabeth A. Lynch, Juli T. Madzsar, Andrew Lin, Anna F. Piotrowski, Elena Pentsova, Jasmine H. Francis, Vaios Hatzoglou, Nikolaus Schultz, Anne S. Reiner, Katherine
Background: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase (BTK). We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary (PCNSL) or secondary CNS lymphoma (SCNSL). Patients and Methods: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined
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CSF1R Inhibition in Patients With Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase 1 Study of Vimseltinib Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Hans Gelderblom, Albiruni Abdul. Razak, Matthew H. Taylor, Todd M. Bauer, Breelyn Wilky, Javier Martín-Broto, Alejandro Falcón. Gonzalez, Piotr Rutkowski, Bartlomiej Szostakowski, Thierry Alcindor, Ramy Saleh, Sofia Genta, Silvia Stacchiotti, Michiel van de Sande, Andrew J. Wagner, Nicholas Bernthal, Lara E. Davis, Jacqueline Vuky, Christopher Tait, Bahar Matin, Supraja Narasimhan, Maitreyi G. Sharma
Purpose: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control
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Eftilagimod alpha (soluble LAG-3 protein) combined with pembrolizumab as second-line therapy for patients with metastatic head and neck squamous cell carcinoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Martin Forster, Irene Brana, Antonio Lopez Pousa, Bernard Doger, Patricia Roxburgh, Pawan Bajaj, Julio Peguero, Matthew Krebs, Enric Carcereny, Grisma Patel, Christian Mueller, Chrystelle Brignone, Frederic Triebel
Purpose: Eftilagimod alpha (efti), a soluble LAG-3 protein, activates antigen-presenting cells (APC) and downstream T-cells. TACTI-002 (Part C) evaluated whether combining efti with pembrolizumab led to strong anti-tumor responses in 2nd line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, while demonstrating good tolerability. Methods: In this multinational phase
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HER2DX Genomic Assay in HER2-positive Early Breast Cancer Treated with Trastuzumab and Pertuzumab: A Correlative Analysis from PHERGain Phase II Trial Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-12 Antonio Llombart-Cussac, José Pérez-García, Fara Brasó-Maristany, Laia Paré, Guillermo Villacampa, Maria Gion, Peter Schmid, Marco Colleoni, Manuel Ruiz. Borrego, Patricia Galván, Joel S. Parker, Wesley Buckingham, Charles M. Perou, Patricia Villagrasa, Jose Antonio. Guerrero, Miguel Sampayo-Cordero, Mario Mancino, Aleix Prat, Javier Cortés
Purpose: To assess the predictive capability of HER2DX assay following (neo)adjuvant trastuzumab-pertuzumab (HP)-based therapy in HER2-positive (HER2+) early breast cancer (EBC). Experimental Design: HER2DX was analyzed in baseline pre-treatment tumors from PHERGain trial. Patients with stage I-IIIA HER2+ EBC were randomized to group A (docetaxel, carboplatin, and HP [TCHP]) and group B (HP ± endocrine
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Increased PVR Expression on Bone Marrow Macrophages May Promote Resistance to TIGIT Blockade in Multiple Myeloma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Ester Lozano, Mari-Pau Mena, Glòria Garrabou, Oriol Cardus, Tania Díaz, David F. Moreno, Joan Mañé Pujol, Aina Oliver-Caldés, Anthony Battram, Natalia Tovar, Maria Teresa Cibeira, Luis Gerardo Rodríguez-Lobato, Joan Bladé, Carlos Fernández de Larrea, Laura Rosinol
Purpose: TIGIT blockade in our ex vivo models of bone marrow (BM) reduced the number of malignant plasma cells (PCs) in only half of patients with multiple myeloma (MM). Here we wanted to investigate whether increased expression of TIGIT ligands may inhibit T cell immune response promoting resistance to TIGIT blockade. Experimental Design: We first characterized the number and phenotype of BM macrophages
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Differences in the prognostic role of age, extent of resection and tumor grade between astrocytoma IDHmt and oligodendroglioma: a single center cohort study Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Thijs van der Vaart, Maarten M.J. Wijnenga, Karin van Garderen, Hendrikus Jan Dubbink, Pim J. French, Marion Smits, Clemens M.F. Dirven, Johan M. Kros, Arnaud J.P.E. Vincent, Martin J. van den Bent
Purpose: IDH-mutant glioma are classified as oligodendroglioma or astrocytoma on the basis of 1p19q-codeletion. Whether prognostic factors are similar between these tumor types is not well understood. Experimental Design: Retrospective cohort study. Molecular characterization was performed with targeted next-generation sequencing. Tumor volumes were calculated using semi-automatic 3D segmentation on
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Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration Resistant Prostate Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-11 Christopher J. Sweeney, Russell Petry, Chang Xu, Merrida Childress, Jie He, David Fabrizio, Ole Gjoerup, Samantha Morley, Timothy Catlett, Zoe June. Assaf, Kobe Yuen, Matthew Wongchenko, Kalpit Shah, Pratyush Gupta, Priti Hegde, Lincoln W. Pasquina, Sanjeev Mariathasan, Ryon P. Graf, Thomas Powles
Purpose: Enzalutamide after abiraterone progression is commonly used in metastatic castration resistant prostate cancer (mCRPC) despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients
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Tumor-localized interleukin-2 and interleukin-12 combine with radiation therapy to safely potentiate regression of advanced malignant melanoma in pet dogs Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-09 Jordan A. Stinson, Matheus Moreno P. Barbosa, Allison Sheen, Noor Momin, Elizabeth Fink, Jordan Hampel, Kim A. Selting, Rebecca L. Kamerer, Keith L. Bailey, K. Dane Wittrup, Timothy M. Fan
Purpose: Interleukin-2 and -12 cytokines have potent anti-cancer activity, but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability to bind and associate with tumor collagen after intratumoral injection potentiated response without toxicity in mice, and was previously safe in pet dogs with sarcoma. Here we sought to test the efficacy of
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Transcriptional phenocopies of deleterious KEAP1 mutations correlate with survival outcomes in lung cancer treated with immunotherapy Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-09 Stefano Scalera, Biagio Ricciuti, Daniele Marinelli, Marco Mazzotta, Laura Cipriani, Giulia Bon, Giulia Schiavoni, Irene Terrenato, Alessandro Di Federico, Joao V. Alessi, Maurizio Fanciulli, Ludovica Ciuffreda, Francesca De Nicola, Frauke Goeman, Giulio Caravagna, Daniele Santini, Ruggero De Maria, Federico Cappuzzo, Gennaro Ciliberto, Mariam Jamal-Hanjani, Mark M. Awad, Nicholas McGranahan, Marcello
Purpose: Co-occurring mutations in KEAP1 and STK11KRAS have emerged as determinants of survival outcomes in non-small cell lung cancer (NSCLC) patients treated with immunotherapy. However, these mutational contexts identify a fraction of non-responders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations, and that
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Tumor Mutational Load: A Novel Predictor for Clinical Benefit of Pembrolizumab Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-08 Fang-Chi Hsu, Yun Yen
A recent study evaluated the efficacy of pembrolizumab across various cancers, classified according to tumor mutational load (TML) defined by whole-genome sequencing. Tumors exhibiting intermediate to high TML showed improved clinical benefit from pembrolizumab. This proof-of-concept study highlights clinical value of TML in patient selection, advancing precision immunotherapy and treatment strategies
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Novel Therapies in Cancer: Trials and Tribulations Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-08 Saiama N. Waqar, Ramaswamy Govindan
Clinical trials are the backbone for advancing therapeutic options for patients diagnosed with cancer. Yet only 7.1% of patients with cancer participate in clinical trials in the United States. We review some of the reasons for poor accrual and discuss potential solutions.
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Streamlined intraoperative brain tumor classification and molecular subtyping in stereotactic biopsies using stimulated Raman histology and deep learning Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-08 David Reinecke, Daniel Ruess, Anna-Katharina Meissner, Gina Fürtjes, Niklas von Spreckelsen, Adrian Ion-Margineau, Florian Khalid, Tobias Blau, Thomas Stehle, Abdulkader Al-Shughri, Reinhard Büttner, Roland Goldbrunner, Maximilian I. Ruge, Volker Neuschmelting
Purpose: Recent artificial intelligence (AI) algorithms aided intraoperative decision-making via stimulated Raman histology (SRH) during craniotomy. This study assesses deep-learning algorithms for rapid intraoperative diagnosis from SRH images in small stereotactic-guided brain biopsies. It defines a minimum tissue sample size threshold to ensure diagnostic accuracy. Experimental Design: A prospective
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Perspectives on drug development for the treatment of chronic myeloid leukemia in pregnant patients and patients who are breastfeeding Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-05 Jorge E. Cortes, Elisabetta Abruzzese, Elyce H. Cardonick, Sonia Hernandez-Diaz, Jamie Gutierrez, Mary Sullivan. Sardegna, Erica Torres-Chavez, Miriam Dinatale, Catherine C. Lerro, Brenda J. Gehrke, Stacy S. Shord, R. Angelo de Claro, Marc R. Theoret, Peter J. DeMaria, Kelly J. Norsworthy
Tyrosine kinase inhibitors (TKI) have improved the outcome and life expectancy of patients with chronic myeloid leukemia (CML). Patients are diagnosed with CML at younger ages, and patients treated for CML may become pregnant or choose to breastfeed. The information available to date on the safety of TKIs during pregnancy and lactation and the optimal management of these patients is largely anecdotal
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PI3K inhibitors in hematology: When one door closes… Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-05 Sigrid S. Skånland, Klaus Okkenhaug, Matthew S. Davids
The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110g and p110d are highly enriched in leukocytes, providing additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kd inhibitor idelalisib was the first of four PI3K inhibitors
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Multiplexed spatial profiling of Hodgkin Reed-Sternberg cell neighborhoods in classic Hodgkin lymphoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-01 Maryam Pourmaleki, Caitlin J. Jones, Sabrina D. Mellinghoff, Brian D. Greenstein, Priyadarshini Kumar, Miguel Foronda, Daniel A. Navarrete, Carl Campos, Mikhail Roshal, Nikolaus Schultz, Sohrab P. Shah, Andrea Schietinger, Nicholas D. Socci, Travis J. Hollmann, Ahmet Dogan, Ingo K. Mellinghoff
Purpose: Classic Hodgkin lymphoma (cHL) is a B cell lymphoma that occurs primarily in young adults and, less frequently, in elderly individuals. A hallmark of cHL is the exceptional scarcity (1-5%) of the malignant Hodgkin Reed-Sternberg (HRS) cells within a network of non-malignant immune cells. Molecular determinants governing the relationship between HRS cells and their proximal microenvironment
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Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-07-01 Andrew T. Lenis, Vignesh Ravichandran, Samantha Brown, Syed M. Alam, Andrew Katims, Hong Truong, Peter A. Reisz, Samantha Vasselman, Barbara Nweji, Karen A. Autio, Michael J. Morris, Susan F. Slovin, Dana Rathkopf, Daniel Danila, Howard I. Scher, Sungmin Woo, Hebert Alberto. Vargas, Vincent P. Laudone, Behfar Ehdaie, Victor Reuter, Maria Arcila, Michael F. Berger, Agnes Viale, Nikolaus Schultz, Anuradha
Purpose: Patients with microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI (TMB-H/MSS). Methods: We sequenced 3,244 tumors from
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A phase I/II study of valemetostat (DS-3201b), an EZH1/2 inhibitor, in combination with irinotecan in patients with recurrent small cell lung cancer Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-28 Noura J. Choudhury, W. Victoria. Lai, Alex Makhnin, Glenn Heller, Juliana Eng, Bob Li, Isabel Preeshagul, Fernando C. Santini, Michael Offin, Kenneth Ng, Paul Paik, Christina Larsen, Michelle S. Ginsberg, Yvonne Lau, Xinyuan Zhang, Marina K. Baine, Natasha Rekhtman, Charles M. Rudin
Purpose: Recurrent small cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted. Patients and Methods: This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety and a recommended phase II dose (RP2D)
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Apalutamide and Goserelin for Androgen Receptor-Positive Salivary Gland Carcinoma: A Phase 2 Nonrandomized Clinical Trial, YATAGARASU Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-28 Yoshitaka Honma, Nobuya Monden, Keisuke Yamazaki, Satoshi Kano, Hironaga Satake, Shigenori Kadowaki, Yoshitaka Utsumi, Tomohiko Nakatogawa, Ryo Takano, Koji Fujii, Yosuke Koroki, Junya Aoyama, Shohei Ouchi, Tetsuro Ogawa, Sharon McCarthy, Sabine D. Brookman-May, Suneel Mundle, Jinhui Li, Daksh Thaper, Toshitaka Nagao, Yuichiro Tada
Purpose: To assess efficacy and safety of apalutamide plus goserelin for androgen receptor (AR)-positive, unresectable or recurrent/metastatic salivary gland carcinoma (URM-SGC). Patients and Methods: This was an open-label, single-arm, multicenter phase II study for patients with AR-positive URM-SGC. The primary endpoint was the overall response rate (ORR) by an independent central radiology review
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A dual-armed oncolytic virus shows clinical efficacy in advanced solid cancers Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-27 Noelia Silva-Pilipich, Cristian Smerdou
An oncolytic adenovirus armed with tumor necrosis factor-α and interleukin-2 was tested in patients with advanced solid tumors. Antitumor effects were observed in both treated and non-treated lesions, leading to long-term survival in some patients. This clinical trial shows the potential of oncolytic virotherapy for patients refractory to standard therapies.
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Maximizing treatment opportunities: assessing protocol waivers’ impact on safety and outcome in the Drug Rediscovery Protocol Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-27 Jade M. van Berge Henegouwen, Laurien J. Zeverijn, Birgit S. Geurts, Louisa R. Hoes, Hanneke van der Wijngaart, Vincent van der Noort, Alwin D.R. Huitema, Filip Y.F. De Vos, Katrien Grünberg, Haiko J. Bloemendal, Henk M.W. Verheul, Emile E. Voest, Hans Gelderblom
Purpose: Although eligibility criteria are essential in trial design, overly restrictive criteria contribute to low accrual and limited generalizability. To enhance trial inclusivity, there has been growing interest in broadening eligibility criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In the Drug Rediscovery Protocol
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Facts and hopes in the systemic therapy of biliary tract carcinomas Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-27 Angela Lamarca, Teresa Macarulla
Biliary tract cancers (BTC) are a heterogeneous group of cancers that continue to present a particularly poor prognosis. Treatment of BTC is rapidly evolving but faces many challenges to improving patient outcomes and maximising benefit from treatment. Only a minority of patients are diagnosed with early-stage disease, and are suitable for curative resection. Current surgical strategies are limited
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Playing Russian Roulette: Parent and Adolescent Perspectives on Tumor Surveillance for Adolescents with Cancer Predisposition Syndromes Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-26 Rachel Elias, Alise Blake, Lori Dean, Jessica S. Flynn, Leila Sachner, Lynn Harrison, Rose McGee, Kim E. Nichols, Katianne M. Howard Sharp
Purpose: Cancer predisposition syndrome (CPS) surveillance allows for the early detection and treatment of neoplasms; however, the psychosocial impact of tumor surveillance is poorly understood for cancer-affected adolescents with a CPS and their parents. To gain insight, we qualitatively characterized the affective and cognitive experience of undergoing CPS tumor surveillance. Experimental Design:
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Combination Targeted Therapy with Lenvatinib and Pembrolizumab in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-26 Jena D. French, Bryan R. Haugen, Francis P. Worden, Daniel W. Bowles, Andrew G. Gianoukakis, Bhavana Konda, Ramona Dadu, Eric J. Sherman, Shaylene McCue, Nathan R. Foster, Yuri E. Nikiforov, Ticiana D. J. Farias, Paul J. Norman, Lori J. Wirth
Purpose: Lenvatinib, a potent multi-kinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC); however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of combination lenvatinib plus pembrolizumab (LP) in these patients. Patients and Methods: We enrolled
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Computational model predicts patient outcomes in Luminal B breast cancer treated with endocrine therapy and CDK4/6 inhibition Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-26 Leonard Schmiester, Fara Brasó-Maristany, Blanca González-Farré, Tomas Pascual, Joaquín Gavilá, Xavier Tekpli, Jürgen Geisler, Vessela N. Kristensen, Arnoldo Frigessi, Aleix Prat, Alvaro Köhn-Luque
Purpose: Development of a computational biomarker to predict, prior to treatment, the response to CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy in patients with breast cancer. Experimental design: A mechanistic mathematical model that accounts for protein signaling and drug mechanisms of action was developed and trained on extensive, publicly available data from breast cancer cell
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Tumor-agnostic genomic and clinical analysis of BRAF fusions identify actionable targets Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-26 Monica F. Chen, Soo-Ryum Yang, Jessica J. Tao, Antoine Desilets, Eli L. Diamond, Clare Wilhelm, Ezra Rosen, Yixiao Gong, Kerry Mullaney, Jean Torrisi, Robert J. Young, Romel Somwar, Helena A. Yu, Mark G. Kris, Gregory J. Riely, Maria E. Arcila, Marc Ladanyi, Mark T.A. Donoghue, Neal Rosen, Rona Yaeger, Alexander Drilon, Yonina R. Murciano-Goroff, Michael Offin
Background: Even though BRAF fusions are increasingly detected in standard multigene next-generation sequencing panels, few reports have explored their structure and impact on clinical course. Patients/methods: We collected data from patients with BRAF fusion-positive cancers identified through a genotyping protocol of 97,024 samples. Fusions were characterized and reviewed for oncogenic potential
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Long-term follow-up of levonorgestrel intrauterine device for atypical hyperplasia and early endometrial cancer reveals relapse characterized by immune exhaustion Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-26 Mikayla Borthwick. Bowen, Brenda Melendez, Qian Zhang, Richard K. Yang, Bryan M. Fellman, Barrett C. Lawson, Naomi N. Adjei, Joseph Celestino, Khalida M. Wani, Bhavana Singh, Diana L. Urbauer, Alexander J. Lazar, Karen H. Lu, Jennifer A. Wargo, Shannon N. Westin, Melinda S. Yates
Background: Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited. Methods: Follow-up data from patients in our prospective phase II trial of LIUD for AH/G1EEC were collected from medical records. Spatial transcriptomics
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TGFβ in pancreas and colorectal cancer: opportunities to overcome therapeutic resistance Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-25 Allan M. Johansen, Steven D. Forsythe, Callum Thomas. McGrath, Grayson Barker, Hugo Jimenez, Ravi K. Paluri, Boris C. Pasche
TGFβ is a pleiotropic signaling pathway, which plays a pivotal role in regulating a multitude of cellular functions. TGFβ has a dual role in cell regulation where it induces growth inhibition and cell death; however, it can switch to a growth-promoting state under cancerous conditions. TGFβ is upregulated in CRC and pancreatic cancer, altering the tumor microenvironment, immune system, and promoting
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Detecting small cell transformation in patients with advanced EGFR mutant lung adenocarcinoma through epigenomic cfDNA profiling Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-24 Talal El Zarif, Catherine B. Meador, Xintao Qiu, Ji-Heui Seo, Matthew P. Davidsohn, Hunter Savignano, Gitanjali Lakshminarayanan, Heather M. McClure, John Canniff, Brad Fortunato, Rong Li, Mandeep K. Banwait, Karl Semaan, Marc Eid, Henry Long, Yin P. Hung, Navin R. Mahadevan, David A. Barbie, Matthew G. Oser, Zofia Piotrowska, Toni K. Choueiri, Sylvan C. Baca, Aaron N. Hata, Matthew L. Freedman, Jacob
Purpose: Histologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sought to develop an epigenomic cell-free (cf)DNA-based approach to non-invasively detect small cell transformation in patients with EGFR mutant (EGFRm) LUAD
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Identification of therapy-induced clonal evolution and resistance pathways in minimal residual clones in multiple myeloma through single-cell sequencing Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-20 Jian Cui, Xiaoyun Li, Shuhui Deng, Chenxing Du, Huishou Fan, Wenqiang Yan, Jingyu Xu, Xiaoqing Li, Tengteng Yu, Shuaishuai Zhang, Rui Lv, Weiwei Sui, Mu Hao, Xin Du, Yan Xu, Shuhua Yi, Dehui Zou, Tao Cheng, Lugui Qiu, Xin Gao, Gang An
Purpose: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA-sequencing (scRNA-seq) to paired diagnostic and post-treatment bone marrow (BM) samples. Experimental Design: scRNA-seq
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Ibrutinib and R-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma of non-GCB type: Phase II clinical trial of the Spanish GELTAMO group Clin. Cancer Res. (IF 10.0) Pub Date : 2024-06-20 Beatriz Rey Búa, Carlos Grande, Jose Javier Sánchez Blanco, Pau Abrisqueta, Antonio Gutiérrez, Ángel Ramírez Páyer, Eva Giné, Izaskun Zeberio Etxetxipia, Maria Jose Terol, Fátima de la Cruz Vicente, Rafael Andreu, María José Ramírez, Adolfo de la Fuente, María Cruz Viguria, María Jesus Peñarrubia, Ana Jiménez-Ubieto, Santiago Montes-Moreno, Armando Lopez-Guillermo, María Dolores Caballero, Alejandro
Purpose: This phase II clinical trial evaluated the combination of Ibrutinib with rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with non-germinal centre B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods: The IBDCL trial (NCT02692248) included patients with histological diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for
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Oral estrogen receptor PROTAC® vepdegestrant (ARV-471) is highly efficacious as monotherapy and in combination with CDK4/6 or PI3K/mTOR pathway inhibitors in preclinical ER+ breast cancer models Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-31 Sheryl M. Gough, John J. Flanagan, Jessica Teh, Monica Andreoli, Emma Rousseau, Melissa Pannone, Mark Bookbinder, Ryan Willard, Kim Davenport, Elizabeth Bortolon, Gregory Cadelina, Deborah Gordon, Jennifer Pizzano, Jennifer Macaluso, Leofal Soto, John Corradi, Katherine Digianantonio, Ieva Drulyte, Alicia Morgan, Connor Quinn, Miklós Békés, Caterina Ferraro, Xin Chen, Gan Wang, Hanqing Dong, Jing Wang
Purpose: Estrogen Receptor (ER) alpha signaling is a known driver of ER-positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Combining endocrine therapy (ET) such as fulvestrant with CDK4/6, mTOR or PI3K inhibitors is now a central strategy for the treatment of ER+ advanced breast cancer. However, suboptimal ER inhibition and resistance resulting from ESR1 mutation
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Intraperitoneal Nivolumab After Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-31 Pauline Corbaux, Gilles Freyer, Olivier Glehen, Benoit You, Naoual Bakrin, Audrey Gelot, David Dayde, Christophe Sajous, Max Piffoux, Julien Peron, Gaelle Lescuyer, Léa Payen, Vahan Kepenekian
Purpose: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be synergistic with intraperitoneal (IP) immunotherapy by increasing tumor antigen expression and mutational load. We assessed the feasibility and safety of IP nivolumab following complete CRS and HIPEC in pretreated patients with recurrent ovarian cancer (ClinicalTrials.gov identifier: NCT03959761)
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CHIPing away at proteomics to find correlations with myeloid neoplasms Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-31 Avni M. Bhalgat, Justin Taylor
Plasma proteomic profiling to identify associations with myeloid neoplasm (MN) risk, highlights the potential of integrating protein and genetic biomarkers for detection individuals at high-risk of developing MN. These proteins also offer valuable insights into biological pathways and inflammatory mechanisms involved in the progression of clonal hematopoiesis (CH) to MN.
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A 5-hydroxymethylcytosine-based non-invasive model for early detection of colorectal carcinomas and advanced adenomas: the METHOD-2 study Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-30 Wenju Chang, Zhou Zhang, Baoqing Jia, Ke-Feng Ding, Zhizhong Pan, Guoqiang Su, Wei Zhang, Tianyu Liu, Yunshi Zhong, Guodong He, Li Ren, Ye Wei, Dongdong Li, Xiaolong Cui, Jun Yang, Yixiang Shi, Marc Bissonnette, Chuan He, Wei Zhang, Jia Fan, Jianmin Xu
Purpose: Detection of colorectal carcinomas (CRC) at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of CRC and advanced adenomas (AA) Experimental Design: Plasma cfDNA samples from 2,576 study participants from the multi-center
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Ultrasound-guided quantitative fluorescence molecular endoscopy for monitoring response in patients with esophageal cancer following neoadjuvant chemoradiotherapy Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-30 Iris Schmidt, Xiaojuan Zhao, Anne M. van der Waaij, Gert Jan Meersma, Frederieke A. Dijkstra, Jan Willem Haveman, Boudewijn van Etten, Dominic J. Robinson, Gursah Kats-Ugurlu, Wouter B. Nagengast
Purpose: The ability to identify residual tumor tissues in patients with locally advanced esophageal cancer (EC) following neoadjuvant chemoradiotherapy (nCRT) is essential for monitoring the treatment response. Using the fluorescent tracer bevacizumab-800CW, we evaluated whether ultrasound-guided quantitative fluorescent molecular endoscopy (US-qFME), which combines quantitative fluorescence molecular
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Exposure-Response and Subgroup Analyses to Support Body Weight-Based Dosing of Brentuximab Vedotin in Children and Young Adults with Newly Diagnosed High-Risk Classical Hodgkin Lymphoma Clin. Cancer Res. (IF 10.0) Pub Date : 2024-05-29 Zufei Zhang, Daping Zhang, Wenchuan Guo, Keenan Fenton, Sujata Narayanan, Shweta Jain, Joy Jiang, Sharon M. Castellino, Kara M. Kelly, Peter D. Cole, Frank G. Keller, Amit Garg, Yen Lin Chia
Purpose: To evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma (cHL) in the phase 3 AHOD1331 study. Patients and Methods: Overall, 296 patients (age 2–21 years) in the overall population were randomized to and received BV