Rxivist logo

Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 173,299 papers from 715,551 authors.

Most downloaded biology preprints, all time

in category oncology

646 results found. For more information, click each entry to expand.

61: SARS-CoV-2 antigen and antibody prevalence among UK staff working with cancer patients during the COVID-19 pandemic.
more details view paper

Posted 20 Sep 2020

SARS-CoV-2 antigen and antibody prevalence among UK staff working with cancer patients during the COVID-19 pandemic.
767 downloads medRxiv oncology

David M Favara, Karen McAdam, Anthony Cooke, Alex Bordessa-Kelly, Ieva Budriunaite, Sophie Bossingham, Sally Houghton, Rainer Doffinger, Nicola Ainsworth, Pippa Corrie

Background International guidelines for testing potentially immunosuppressed cancer patients receiving non-surgical anticancer therapies for SARS-CoV-2 (COVID-19) are currently lacking. The value of routinely testing staff treating cancer patients is not known. Methods: Patient-facing oncology department staff at work during the COVID-19 pandemic consented to have a nasopharyngeal swab SARS-CoV-2 antigen test by polymerase chain reaction (PCR) and blood tests for SARS-CoV-2 antibody using a laboratory Luminex-based assay and a rapid point-of-care (POC) assay on 2 occasions 28 days apart in June and July 2020. Results 434 participants were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%) and administrators (10.1%). 82% were female; median age 40-years (range 19-66). 26.3% reported prior symptoms suggestive of SARS-CoV-2 infection and 1.4% tested PCR-positive prior to June 2020. All were PCR-negative at both study day 1 and 28. 18.4% were SARS-CoV-2 sero-positive on day 1 by Luminex, of whom 42.5% also tested positive by POC. 47.5% of Luminex sero-positives had antibodies to both nucleocapsid (N) and surface (S) antigens. Nurses (21.3%) and doctors (17.4%) had higher prevalence trends of Luminex sero-positivity compared with administrators (13.6%) and radiographers (8.9%) (p=0.2). 38% of sero-positive participants reported previous symptoms suggestive of SARS-CoV-2 infection, a 1.9-fold higher odds than sero-negative participants (p=0.01). 400 participants re-tested on day 28: 13.3% were Luminex sero-positive of whom 92.5% were previously positive and 7.5% newly positive. Nurses (16.5%) had the highest seroprevalence trend amongst staff groups (p=0.07). 32.5% of day 1 sero-positives became sero-negative by day 28: the majority being previously reactive to the N-antigen only (p<0.0001). Conclusion The high prevalence of SARS-CoV-2 IgG sero-positivity in oncology nurses, and the high decline of positivity over 4 weeks supports regular antigen and antibody testing in this staff group for SARS-CoV-2 as part of routine patient care prior to availability of a vaccine.

62: Griffin: Framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
more details view paper

Posted 03 Sep 2021

Griffin: Framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA
766 downloads medRxiv oncology

Anna-Lisa Doebley, Minjeong Ko, Hanna Liao, A Eden Cruikshank, Caroline Kikawa, Katheryn Santos, Joseph Hiatt, Robert D Patton, Navonil De Sarkar, Anna C Hoge, Katharine Chen, Zachary T Weber, Mohamed Adil, Jonathan Reichel, Paz Polak, Viktor A Adalsteinsson, Peter S Nelson, Heather A. Parsons, Daniel A Stover, David MacPherson, Gavin Ha

Cell-free DNA (cfDNA) has the potential to inform tumor subtype classification and help guide clinical precision oncology. Here we developed Griffin, a new method for profiling nucleosome protection and accessibility from cfDNA to study the phenotype of tumors using as low as 0.1x coverage whole genome sequencing (WGS) data. Griffin employs a novel GC correction procedure tailored to variable cfDNA fragment sizes, which improves the prediction of chromatin accessibility. Griffin achieved excellent performance for detecting tumor cfDNA in early-stage cancer patients (AUC=0.96). Next, we applied Griffin for the first demonstration of estrogen receptor (ER) subtyping in metastatic breast cancer from cfDNA. We analyzed 254 samples from 139 patients and predicted ER subtype with high performance (AUC=0.89), leading to insights about tumor heterogeneity. In summary, Griffin is a framework for accurate clinical subtyping and can be generalizable to other cancer types for precision oncology applications.

63: Proteogenomics of glioblastoma associates molecular patterns with survival
more details view paper

Posted 03 May 2020

Proteogenomics of glioblastoma associates molecular patterns with survival
765 downloads medRxiv oncology

Gali Yanovich-Arad, Paula Ofek, Eilam Yeini, Artem Danilevsky, Noam Shomron, Rachel Grossman, Ronit Satchi-Fainaro, Tamar Geiger

Glioblastoma (GBM) is the most aggressive form of glioma, with poor prognosis exhibited by most patients, and a median survival time of less than two years. To examine survival-associated patterns, we assembled a cohort of 87 GBM patients whose survival ranges from less than 3 months and up to 10 years, most of which are not bearing isocitrate-dehyderogenase (IDH)-1 mutation and did not undergo prior treatment. We integrated high-resolution mass-spectrometry proteomics and RNA-sequencing to examine the yet unresolved proteomic contribution to poor patient outcome, and compared it to the more established transcriptomic contribution and to published single-cell RNA-sequencing data. Discovering both layer-specific and shared processes, we found that immune, metabolic and developmental processes distinguish short and long survival periods. Additionally, we observed a significant discrepancy in tumor classification between expression layers. Overall, our integrative findings establish proteomic heterogeneity in GBM as a gateway to understanding poor patient survival.

64: COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area
more details view paper

Posted 05 May 2020

COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area
762 downloads medRxiv oncology

Perrine Vuagnat, Maxime Frelaut, Toulsie Ramtohul, Clemence Basse, Sarah Diakite, Aurelien Noret, Audrey Bellesoeur, Vincent Servois, Delphine Hequet, Enora Laas, Youlia Kirova, Luc Cabel, Jean-Yves Pierga, Institut Curie Breast Cancer and COVID Group, Laurence Bozec, Xavier Paoletti, Paul Cottu, Francois-Clement Bidard

Background: Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods: An IRB-approved prospective registry was set up at ICH on March 13th, 2020 for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features and outcome. Data extraction was done on April 25th, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT-scan abnormalities. Results: Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N=41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (>70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions: This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.

65: Single-cell transcriptomics predicts relapse in MLL-rearranged acute lymphoblastic leukemia in infants
more details view paper

Posted 17 Apr 2020

Single-cell transcriptomics predicts relapse in MLL-rearranged acute lymphoblastic leukemia in infants
756 downloads medRxiv oncology

Tito Candelli, Pauline Schneider, Patricia Garrido Castro, Luke A. Jones, Rob Pieters, Thanasis Margaritis, Ronald W. Stam, Frank C. P. Holstege

Infants with MLL-rearranged acute lymphoblastic leukemia (ALL) undergo intense therapy to counter a highly aggressive leukemia with survival rates of only 30-40%. The majority of patients initially show therapy response, but in two-thirds of cases the leukemia returns, typically during treatment. Accurate relapse prediction would enable treatment strategies that take relapse risk into account, with potential benefits for all patients. Through analysis of diagnostic bone marrow biopsies, we show that single-cell RNA sequencing can predict future relapse occurrence. By analysing gene modules derived from an independent study of the gene expression response to the key drug prednisone, individual leukemic cells are predicted to be either resistant or sensitive to treatment. Quantification of the proportion of cells classified by single-cell transcriptomics as resistant or sensitive, accurately predicts the occurrence of future relapse in individual patients. Strikingly, the single-cell based classification is even consistent with the order of relapse timing. These results lay the foundation for risk-based treatment of MLL-rearranged infant ALL, through single-cell classification. This work also sheds light on the subpopulation of cells from which leukemic relapse arises. Leukemic cells associated with high relapse risk are characterized by a smaller size and a quiescent gene expression program. These cells have significantly fewer transcripts, thereby also demonstrating why single-cell analyses may outperform bulk mRNA studies for risk stratification. This study indicates that single-cell RNA sequencing will be a valuable tool for risk stratification of MLL-rearranged infant ALL, and shows how clinically relevant information can be derived from single-cell genomics.

66: Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients
more details view paper

Posted 21 May 2020

Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients
754 downloads medRxiv oncology

Maria Gonzalez-Cao, Monica Antonazas-Basa, Teresa Puertolas, Eva Munoz-Couselo, Jose Luis Manzano, Cristina Carrera, Ivan Marquez-Rodas, Pilar Lopez-Criado, Juan Francisco Rodriguez-Moreno, Almudena Garcia-Castano, Juan Martin-Liberal, Pedro Rodriguez-Jimenez, Susana Puig, Pablo Cerezuela, Marta Feito-Rodriguez, Belen Rubio-Viqueira, Guillermo Crespo, Pablo Luna-Fra, Cristina Aguayo, Pablo Ayala de Miguel, Rosa Feltes, Lara Valles, Ana Drozdowskyj, Ainara Soria, Cayetana Maldonado, Luis Fernandez-Morales, Rafael Rosell, Mariano Provencio, Alfonso Berrocal

Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic

67: Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis
more details view paper

Posted 06 May 2020

Cancer is associated with the severity and mortality of patients with COVID-19: a systematic review and meta-analysis
751 downloads medRxiv oncology

Ya Gao, Ming Liu, Shuzhen Shi, Yamin Chen, Yue Sun, Ji Chen, Jinhui Tian

Background: Cancer patients are considered a highly vulnerable population in the COVID-19 epidemic, but the relationship between cancer and the severity and mortality of patients with COVID-19 remains unclear. This study aimed to explore the prevalence of cancer in patients with COVID-19 and to examine whether cancer patients with COVID-19 may be at an increased risk of severe illness and mortality. Methods: A comprehensive electronic search in seven databases was performed, to identified studies reporting the prevalence of cancer in COVID-19 patients, or providing data of cancer between patients with severe or non-severe illness or between non-survivors and survivors. Meta-analyses were performed to estimate the pooled prevalence and odds risk (OR) using the inverse variance method with the random-effects model. Results: Thirty-four studies with 8080 patients were included. The pooled prevalence of cancer in patients with COVID-19 was 2.0% (95% CI: 2.0% to 3.0%). The prevalence in Italy (5.0%), France (6.0%), and Korea (4.0%) were higher than that in China (2.0%). Cancer was associated with a 2.84-fold significantly increased risk of severe illness (OR = 2.84, 95%CI: 1.75 to 4.62, P < 0.001) and a 2.60-fold increased risk of death (OR = 2.60, 95%CI: 1.28 to 5.26, P = 0.008) in patients with COVID-19. Sensitivity analyses showed that the results were stable after excluding studies with a sample size of less than 100. Conclusions: Cancer patients have an increased risk of COVID-19 and cancer was associated with a significantly increased risk of severity and mortality of patients with COVID-19.

68: Everolimus improves the efficacy of dasatinib in the treatment of PDGFRA-driven glioma
more details view paper

Posted 02 Jan 2020

Everolimus improves the efficacy of dasatinib in the treatment of PDGFRA-driven glioma
751 downloads medRxiv oncology

Zachary Miklja, Vivek Nand Yadav, Rodrigo Cartaxo, Ruby Siada, Chase C. Thomas, Jessica R Cummings, Brendan Mullan, Stefanie Stallard, Alyssa Paul, Amy K. Bruzek, Kyle Wierzbicki, Tao Yang, Taylor Garcia, Ian Wolfe, Marcia Leonard, Patricia L. Robertson, Hugh Garton, Daniel R Wahl, Hemant Parmar, Jann N. Sarkaria, Cassie Kline, Sabine Mueller, Theodore Nicolaides, Chandan Glasser, Sarah E.S. Leary, Sriram Venneti, Chandan Kumar-Sinha, Arul Chinnaiyan, Rajen Mody, Pai P. Manjunath, Timothy N. Phoenix, Bernard L. Marini, Carl Koschmann

BackgroundPediatric and adult high-grade glioma (HGG) frequently harbor PDGFRA alterations. Treatment of PDGFRA-driven HGG with targeted agents, such as the tyrosine kinase inhibitor dasatinib, has failed in the clinic. We hypothesized that co-treatment with everolimus may improve the efficacy of dasatinib in PDGFRA-driven glioma through combinatorial synergism and increased tumor accumulation of dasatinib. MethodsDose response, synergism studies, P-gp inhibition and pharmacokinetic studies were performed on in vitro and in vivo human and mouse models of HGG. De novo tumors were generated in mice using intra-uterine electroporation (IUE) by injecting PB plasmids of TP53 mutation, PDGFRA mutation and H3K27M mutation (PPK) in the lateral vertical of mice embryos. Two children with recurrent PDGFRA-driven HGG were treated with dasatinib and everolimus with correlate CSF analysis. ResultsDasatinib effectively inhibited the proliferation of mouse and human primary HGG cells with a dose-dependent reduction of PDGFRA and pPDGFRA. Dasatinib exhibited synergy with everolimus in the treatment of HGG cells at low nanomolar concentrations of both agents. Prolonged exposure to everolimus significantly improved the CNS retention of dasatinib and extended survival of PPK tumor bearing mice. Two children with recurrent PDGFRA-driven HGG treated with dasatinib and everolimus survived six months and nine months after progression. A paired CSF sample from the patient with PDGFRA-amplified HGG showed 50% increase in CSF dasatinib levels after the addition of everolimus. ConclusionEfficacy of dasatinib treatment of PDGFRA-driven HGG is improved with everolimus and suggests a promising route for improving targeted therapy for this patient population. Trial RegistrationClinicalTrials.gov NCT03352427 FundingThe authors thank the patients and their families for participation in this study. CK is supported by NIH/NINDS K08-NS099427-01, the University of Michigan Chad Carr Pediatric Brain Tumor Center, the Chad Tough Foundation, Hyundai Hope on Wheels and Catching up with Jack. The PEDS-MIONCOSEQ study was supported by grant 1UM1HG006508 from the National Institutes of Health Clinical Sequencing Exploratory Research Award (PI: Arul Chinnaiyan).

69: Emotional health concerns of oncology physicians in the United States: fallout during the COVID-19 pandemic
more details view paper

Posted 12 Jun 2020

Emotional health concerns of oncology physicians in the United States: fallout during the COVID-19 pandemic
748 downloads medRxiv oncology

Lauren Thomaier, Deanna Teoh, Patricia Jewett, Heather Beckwith, Helen Parsons, Jianling Yuan, Anne H. Blaes, Emil Lou, Jane Yuet Ching Hui, Rachel I. Vogel

Introduction: Cancer care is significantly impacted by the Coronavirus Disease 2019 (COVID-19) pandemic. Our objective was to evaluate the effect of the pandemic on the emotional well-being of oncology providers across the United States and explore factors associated with anxiety and depression symptoms. Methods and Materials: A cross-sectional survey was administered to United States cancer-care physicians recruited over a two-week period (3/27/2020-4/10/2020) using snowball-convenience sampling through social media. Symptoms of anxiety and depression were measured using the Patient Health Questionnaire (PHQ-4). Results: Of 486 participants, 374 (77.0%) completed the PHQ-4: mean age 45.7 +/- 9.6 years; 63.2% female; all oncologic specialties were represented. The rates of anxiety and depression symptoms were 62.0% and 23.5%, respectively. Demographic factors associated with anxiety included female sex, younger age, and less time in clinical practice. Perception of inadequate PPE (68.6% vs. 57.4%, p=0.03) and practicing in a state with more COVID-19 cases (65.8% vs. 51.1%, p=0.01) were associated with anxiety symptoms. Factors significantly associated with both anxiety and depression included: degree to which COVID-19 has interfered with the ability to provide treatment to cancer patients and concern that patients will not receive the level of care needed for non-COVID-19 illness (all p-values <0.01). Conclusion: The prevalence of anxiety and depression symptoms among oncology physicians in the United States during the COVID-19 pandemic is high. Our findings highlight factors associated with and sources of psychological distress to be addressed to protect the well-being of oncology physicians.

70: Early Outcomes of Preoperative 5-fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection
more details view paper

Posted 23 Mar 2020

Early Outcomes of Preoperative 5-fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection
747 downloads medRxiv oncology

Shireen Parsai, Joshua Lawrenz, Scott Kilpatrick, Brian Rubin, Cory Hymes, Michele Gray, Nathan Mesko, Chirag Shah, Lukas Nystrom, Jacob G Scott

Purpose/ObjectivesThere are limited data regarding the use of hypofractionated radiation therapy (RT) for soft tissue sarcoma. We report early oncologic outcomes and wound complications of patients undergoing preoperative hypofractionated (5 fraction) RT followed by immediate surgical resection. Materials/MethodsAn IRB-approved database of patients treated with preoperative RT for soft tissue sarcoma was queried. Patients treated with a hypofractionated dosing regimen followed by immediate (within 7 days) planned wide surgical resection were identified. ResultsBetween 2016 to 2019, sixteen patients met eligibility criteria. The median clinical follow-up was 10.7 months (range 1.7-33.2). The median patient age was 64 years old (range 33-88). Ten of the sarcomas were located in the lower extremity, 4 in the upper extremity, and two were located in the trunk. Five patients had metastatic disease at diagnosis. The majority of the patients received a total radiation dose of 30 Gy in 5 fractions (range 27.5-40 Gy) on consecutive days. All patients were planned with IMRT/VMAT. The median time to surgical resection following the completion of RT was 1 day (range 0-7 days). The median time from initial biopsy results to completion of primary oncologic therapy was 20 days (range 16-35). Ten patients achieved R0 resection, whereas the remaining 6 patients achieved R1 resection. Of the 13 patients assessed for local control, no patients developed local failure. Five patients developed wound healing complications (31%), of which only three patients (19%) required return to the operating room. ConclusionsTreatment of soft tissue sarcoma with preoperative hypofractionated RT followed by immediate resection resulted in a median of 20 days from biopsy results to completion of oncologic therapy. Early outcomes demonstrate favorable wound healing. Further prospective data with long-term follow-up is required to determine the oncologic outcomes and toxicity of hypofractionated preoperative RT.

71: Seroconversion rates following COVID-19 vaccination amongst patients with malignant disease- the impact of diagnosis and cancer-directed therapies
more details view paper

Posted 14 May 2021

Seroconversion rates following COVID-19 vaccination amongst patients with malignant disease- the impact of diagnosis and cancer-directed therapies
742 downloads medRxiv oncology

Astha Thakkar, Jesus Gonzalez Lugo, Niyati Goradia, Radhika Gali, Lauren C. Shapiro, Kith Pradhan, Shafia Rahman, So Yeon Kim, Brian Ko, R.Alejandro Sica, Noah Kornblum, Lizamarie Bachier-Rodriguez, Margaret McCort, Sanjay Goel, Roman Perez-Soler, Stuart Packer, Joseph Sparano, Benjamin Gartrell, Della Makower, Yitz D Goldstein, Lucia Wolgast, Amit Verma, Balazs Halmos

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post-vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.

72: Efficacy of SARS-CoV-2 vaccine in thoracic cancer patients: a prospective study supporting a third dose in patients with minimal serologic response after two vaccine doses
more details view paper

Posted 13 Aug 2021

Efficacy of SARS-CoV-2 vaccine in thoracic cancer patients: a prospective study supporting a third dose in patients with minimal serologic response after two vaccine doses
736 downloads medRxiv oncology

Valerie GOUNANT, Valentine Marie FERRE, Ghassen SOUSSI, Charlotte charpentier, Heloise FLAMENT, Nadhira FIDOUH, Gilles COLLIN, Celine NAMOUR, Sandra ASSOUN, Alexandra BIZOT, Zohra BROUK, Eric VICAUT, Luis TEXEIRA, Diane DESCAMPS, Gerard ZALCMAN

Hypothesis Coronavirus disease 2019 (COVID-19) resulted in a 30% mortality rate in thoracic cancer patients. Given that cancer patients were excluded from serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine registration trials, it is still unknown whether they would develop a protective anti-spike antibody response following vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to SARS-CoV2 vaccine in thoracic cancer patients. Methods SARS-CoV2-spike antibodies were measured using Abbot ARCHITECT SARS-CoV-2 IgG immunoassay, prior to first injection of BNT162b2 mRNA vaccine, as well as at Week 4, and two-to-sixteen weeks after second vaccine dose. The factors associated with antibody response were analyzed. Results Overall, 306 patients, with a median age of 67.0 years (IQR=58-74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After 4.7-month median follow-up, seven patients (2.3%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of 269 serological results available beyond Day 14 post-second vaccine dose, 17 (6.3%) were still negative (<50 AU/mL) (arbitrary units/mL), while 34 (11%) were <300 AU/mL (12.5th percentile). In multivariate analysis, only age and chronic corticosteroid treatment were significantly associated with a lack of immunization. Thirty patients received a third vaccine dose, with only three patients showing persistent negative serology thereafter, whereas the others demonstrated clear seroconversion. Conclusion SARS-CoV2 vaccines were shown to be efficient in thoracic cancer patients, most of them being immunized after two doses. A third shot given to 11% of patients with persistent low antibody titers resulted in a 88% immunization rate.

73: Obesity paradox in patients with cancer: A systematic review and meta-analysis of 6,320,365 patients
more details view paper

Posted 02 May 2020

Obesity paradox in patients with cancer: A systematic review and meta-analysis of 6,320,365 patients
731 downloads medRxiv oncology

Fausto Petrelli, Alessio Cortellini, Alice Indini, Gianluca Tomasello, Michele Ghidini, Olga Nigro, Massimiliano Salati, Lorenzo Dottorini, Alessandro Iaculli, Antonio Varricchio, Valentina Rampulla, Sandro Barni, Antonio Bossi, Antonio Ghidini, Alberto Zaniboni

BACKGROUND. Obesity, defined as a body mass index (BMI) [&ge;] 30 kg/m2, is associated with a significant increase in risk of many cancers. In last years, various studies suggested that obese cancer patients have better outcomes than non obese patients. This phenomenon, also known as the obesity paradox, is not well understood and presents controversial explanations. We performed a systematic review and metaanalysis to assess the association between obesity and outcome after a diagnosis of cancer. PATIENTS AND METHODS. PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020, for studies reporting prognosis of patients with obesity and cancer. Risk of death, cancer specific survival (CSS) and progression were pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI). The primary outcome of the study refers to overall survival (OS) in obese vs non obese patients with malignancies. Secondary endpoints were CSS and progression or disease free survival (PFS or RFS). RESULTS. Mortality and relapse associated with obesity in patients with cancer were evaluated among n=6,320,365 participants (n=203 studies). Overall, association of obesity and cancer was associated with a reduced OS (HR =1.14, 95% CI: 1.09 1.19; P<.01) and CSS (HR=1.17, 95%CI 1.12 1.23; P<.01). Patients were also at increased risk for relapse (HR=1.13, 95%CI 1.07 1.19; P<.01). Patients with breast, colorectal and uterine tumors were at increased risk of death. Conversely, obese with lung cancer, renal cell carcinoma and melanoma survived longer that non obese. CONCLUSIONS. In many cancer patients, obesity reduces survival and increases the risk of relapse. In lung cancer, renal cell carcinoma and melanoma obesity was protective in terms of outcome. More intensive follow up, adequate dosing of oncological treatments, calories intake restrictions, physical activity and monitoring of obesity related complications are effective measures for reducing mortality in these subjects.

74: Mindfulness-Based Stress Reduction for Breast Cancer Survivors (MBSR (BC)): Evaluating Mediators of Psychological and Physical Outcomes in a Large Randomized Controlled Trial
more details view paper

Posted 09 May 2020

Mindfulness-Based Stress Reduction for Breast Cancer Survivors (MBSR (BC)): Evaluating Mediators of Psychological and Physical Outcomes in a Large Randomized Controlled Trial
730 downloads medRxiv oncology

Cecile A. Lengacher, L. Forest Gruss, Kevin E Kip, Richard R. Reich, Manolete S. Moscoso, Katterine G. Chauca, Anisha Joshi, Pinky Budhrani Shani, Lakeshia Cousin, Carly Paterson Khan, Matthew Goodman, Jong Y. Park

MBSR(BC) is known to have a positive impact on psychological and physical symptoms among breast cancer survivors (BCS). However, the cognitive mechanisms of how MBSR(BC) works are unknown. The purpose of this study, as part of a larger R01 trial, was to test whether positive effects achieved from the MBSR(BC) program were mediated through changes in increased mindfulness, decreased fear of breast cancer recurrence, and perceived stress. Female BCS >21 years diagnosed with Stage 0-III breast cancer were randomly assigned to a 6-week MBSR(BC) or a Usual Care(UC) regimen. Potential outcome mediators were identified by use of an analysis of covariance (ANCOVA), comparing mean values of outcome variables and potential mediating variables followed by mediational and bootstrap analyses. Among 322 BCS (167 MBSR(BC) and 155 UC), fear of recurrence and perceived stress, but not mindfulness, mediated reductions in anxiety and fatigue at weeks 6 and 12, partially supporting our hypothesis of cognitive mechanisms of MBSR(BC).

75: Network-based assessment of HDAC6 activity is highly predictive of pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat
more details view paper

Posted 28 Apr 2020

Network-based assessment of HDAC6 activity is highly predictive of pre-clinical and clinical responses to the HDAC6 inhibitor ricolinostat
725 downloads medRxiv oncology

tizita zeleke, Qingfei Pan, Cody Chiuzan, Maika Onishi, Mariano Alvarez, Erin Honan, Min Yang, Pei Ling Chia, Partha Mukhopadhyay, Sean Kelly, Ruby Wu, Kathleen Fenn, Meghna Trivedi, Melissa Accordino, Katherine Crew, Dawn Hershman, Matthew Maurer, P. Simon Jones, Andrea Califano, Kevin Kalinsky, Jiyang Yu, jose silva

Despite the anticancer activity of pan-histone deacetylase (HDAC) inhibitors, their clinical use has been limited due to toxicity. However, the development of more specific inhibitors that selectively inhibit individual HDACs is emerging as a novel and well-tolerated alternative. Here, we present the results of the first clinical trial evaluating the activity of ricolinostat (the leading HDAC6 inhibitor) in breast cancer (BC) patients. We have developed a computational network-based algorithm to evaluate the activity of the HDAC6 protein, based on the enrichment of its transcriptional targets in differentially expressed genes (HDAC6 score). Through preclinical in vitro and in vivo studies, we confirmed that the HDAC6 score can stratify the sensitivity of BC cells to ricolinostat treatment and may thus have value as a predictive biomarker. Moreover, analysis of ~3,000 primary human breast cancers showed that ~30% of them present high HDAC6 scores. Based on these results, we designed a phase Ib clinical trial to evaluate the activity of ricolinostat plus nab-paclitaxel in metastatic BC patients. Study results showed that the two agents can be safely combined, that clinical activity is identified specifically in patients with HR+/HER2- disease, and that the HDAC6 score was predictive of response. Expansion of our analysis to other tumor types identified multiple cohorts enriched in high HDAC6 score samples. These results suggest that the HDAC6 score may provide an effective, CLIA certified predictive biomarker of ricolinostat sensitivity in multiple human cancers.

76: Predicting the effect of statins on cancer risk using genetic variants: a Mendelian randomization study in UK Biobank
more details view paper

Posted 29 Feb 2020

Predicting the effect of statins on cancer risk using genetic variants: a Mendelian randomization study in UK Biobank
723 downloads medRxiv oncology

Paul Carter, Mathew Vithayathil, Siddhartha Kar, Rahul Potluri, Amy M Mason, Susanna C Larsson, Stephen Burgess

Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. We here assess the potential effect of statin therapy on cancer risk in Mendelian randomization analyses. We obtained genetic associations with the risk of overall and 22 site-specific cancers for 367,703 individuals in UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (OR per 1 standard deviation increase in LDL-cholesterol 1.32, 95% CI 1.13-1.53, p=0.0003), but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically-predicted LDL-cholesterol was not associated with overall cancer risk (OR 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk, but other lipid-lowering treatments do not. This suggests that statins reduce cancer risk through a cholesterol independent pathway.

77: Clinical phenotypes and prognostic features of ETMRs (Embryonal Tumor with Multi-layered Rosettes) a new CNS tumor entity: A Rare Brain Tumor Registry study
more details view paper

Posted 15 Aug 2020

Clinical phenotypes and prognostic features of ETMRs (Embryonal Tumor with Multi-layered Rosettes) a new CNS tumor entity: A Rare Brain Tumor Registry study
703 downloads medRxiv oncology

Annie Huang

Background ETMRs are a newly recognized rare paediatric brain tumor with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and limited clinical data, disease features and determinants of outcome are poorly defined. We performed an integrated clinico-pathologic and molecular analyses of 159 primary ETMRs to define clinical phenotypes, identify predictors of survival and critical treatment modalities for this orphan disease. Methods Primary ETMR patients were identified from the Rare Brain Tumor Consortium (rarebraintumorconsortium.ca) global registry using histopathologic and molecular assays. Event-Free (EFS) and Overall Survival (OS) for 108 patients treated with curative multi-modal regimens were determined using Cox proportional hazard and log rank analyses. Findings ETMRs were predominantly non-metastatic (73%) tumors arising from multiple sites; 55% were cerebral tumors, 45% arose at sites characteristic of other brain tumors. Hallmark C19MC alterations were seen in 91%; 9% were ETMR-NOS. Survival and hazard analyses showed a 6 month median EFS and 2-4yr OS of 27-29% with metastatic disease (HR=0.44, 95% CI 0.26-0.74; p=0.002) and brainstem location (HR=0.40, 95% CI 0.021-0.75; p=0.005) correlating with adverse OS. Gross total resection (GTR: HR=0.38, 95% CI 0.21-0.68; p=0.001), high dose chemotherapy (HDC: HR=0.55, 95% CI 0.31-0.97; p=0.04) and radiation (RT: HR=0.32, 95% CI 0.16-0.60; p=<0.001) correlated with improved EFS and OS in multi-variable analyses. EFS and OS for patients treated with only conventional dose chemotherapy (CC) was 0% and respectively 37%+/-14% and 32%+/-13% for patients treated with HDC. Patients with GTR or sub-total resection (STR) treated with HDC and RT had superior EFS (GTR 73%+/-14%, p=0.018; STR 67%+/-19% p=0.009) and OS (GTR 66%+/-17%, p=0.05; STR 67%+/-16%, p=0.005). Amongst 21 long-term survivors (OS 24-202 months); 38%, 24% and 24% respectively received craniospinal, focal or no RT. Interpretation: Prompt molecular diagnosis and post-surgical treatment with multi-modal therapy tailored to patient-specific risk features improves ETMR survival.

78: Discriminative Subtyping of Lung Cancers from Histopathology Images via Contextual Deep Learning
more details view paper

Posted 26 Jun 2020

Discriminative Subtyping of Lung Cancers from Histopathology Images via Contextual Deep Learning
676 downloads medRxiv oncology

Benjamin J Lengerich, Maruan Al-Shedivat, Amir Alavi, Jennifer Williams, Sami Labbaki, Eric P Xing

When designing individualized treatment protocols for cancer patients, clinicians must synthesize the information from multiple data modalities into a single parsimonious description of the patient's personal disease. However, such a description of a patient is never observed. In this work, we propose to model these patient descriptions as latent \emph{discriminative subtypes}---sample representations which can be learned from one data modality and used to contextualize predictions based on another data modality. We apply contextual deep learning to learn these sample-specific discriminative subtypes from lung cancer histopathology imagery. Based on these subtypes, we produce sample-specific transcriptomic models which accurately classify samples as adenocarcinoma, squamous cell carcinoma, or healthy tissue (F1 score of 0.97, outperforming previous state-of-the-art multimodal approaches). Combining these data modalities in a single pipeline not only improves the predictive accuracy, but also gives biological interpretations of the discriminative subtypes and ties the phenotypic patterns present in histopathology images to biological processes.

79: Metabolic characterization of plasma and cyst fluid from cystic precursors to pancreatic cancer patients reveal metabolic signatures of bacterial infection
more details view paper

Posted 04 Nov 2020

Metabolic characterization of plasma and cyst fluid from cystic precursors to pancreatic cancer patients reveal metabolic signatures of bacterial infection
663 downloads medRxiv oncology

Ann Morgell, Julie A Reisz, Zeeshan Ateeb, Haleh Davanian, Susanne E. Reinsbach, Asif Halimi, Rogier Gaiser, Roberto Valente, Urban Arnelo, Marco Del Chiaro, Margaret Sällberg Chen, Angelo D'Alessandro

Pancreatic cancer is the seventh leading cause of cancer-related death worldwide, with a 5-year survival rate as low as 9%. One factor complicating the management of pancreatic cancer is the lack of reliable tools for early diagnosis. While up to 50% of the adult population has been shown to develop precancerous pancreatic cysts, limited and insufficient approaches are currently available to determine whether a cyst is going to progress into pancreatic cancer. Recently, we used metabolomics approaches to identify candidate markers of disease progression in patients diagnosed with intraductal papillary mucinous neoplasms (IPMNs) undergoing pancreatic resection. Here we enrolled an independent cohort to verify the candidate markers from our previous study with orthogonal quantitative methods in plasma and cyst fluid from serous cystic neoplasm and IPMN (either low- or high-grade dysplasia or pancreatic ductal adenocarcinoma). We thus validated these markers with absolute quantitative methods through the auxilium of stable isotope-labelled internal standards in a new independent cohort. Finally, we identified novel markers of IPMN status and disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products and TMAO. We show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. Overall, our findings are interesting per se, owing to the validation of previous markers and identification of novel small molecule signatures of IPMN and disease progression. In addition, our findings further fuel the provoking debate as to whether bacterial infections may represent an etiological contributor to the development and severity of the disease in pancreatic cancer, in like fashion to other cancers (e.g., Helicobacter pylori and gastric cancer). Key pointsO_LIWe identified and quantified novel markers of IPMN cyst status and pancreatic cancer disease progression - including amino acids, carboxylic acids, conjugated bile acids, free and carnitine-conjugated fatty acids, purine oxidation products and TMAO. C_LIO_LIWe show that the levels of these metabolites of potential bacterial origin correlated with the degree of bacterial enrichment in the cyst, as determined by 16S RNA. C_LI

80: Meningioma epigenetic grouping reveals biologic drivers and therapeutic vulnerabilities
more details view paper

Posted 27 Nov 2020

Meningioma epigenetic grouping reveals biologic drivers and therapeutic vulnerabilities
656 downloads medRxiv oncology

Abrar Choudhury, Stephen T Magill, Charlotte D Eaton, Briana C Prager, William C Chen, Kyounghee Seo, Calixto-Hope G Lucas, Javier E Villaneuva-Meyer, Tai-Chung Lam, Jenny Kan-Suen Pu, Lai-Fung Li, Gilberto Ka-Kit Leung, Harish N. Vasudevan, S. John Liu, Jason W Chan, Zhixin Qiu, Michael Y Zhang, Michael V Martin, Matthew S Susko, Steve E Braunstein, Nancy Ann Oberheim Bush, Jessica Schulte, Nicholas Butowski, Penny K Sneed, Mitchel S Berger, Arie Perry, Joanna J. Phillips, David A. Solomon, Joseph F Costello, Michael W McDermott, Jeremy N Rich, David R. Raleigh

Meningiomas arising from the meningothelial central nervous system lining are the most common primary intracranial tumors, and a significant cause of neurologic morbidity and mortality. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of meningioma biology. DNA methylation profiling provides robust classification of central nervous system tumors, and can elucidate targets for molecular therapy. Here we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, and single-cell approaches to show meningiomas are comprised of 3 epigenetic groups with distinct clinical outcomes and biological features informing new treatments for meningioma patients. Merlin-intact meningiomas (group A, 34%) have the best outcomes and are distinguished by a novel apoptotic tumor suppressor function of NF2/Merlin. Immune-enriched meningiomas (group B, 38%) have intermediate outcomes and are distinguished by immune cell infiltration, HLA expression, and lymphatic vessels. Hypermitotic meningiomas (group C, 28%) have the worst outcomes and are distinguished by convergent genetic mechanisms misactivating the cell cycle. Consistently, we find cell cycle inhibitors block meningioma growth in cell culture, organoids, xenografts, and patients. Our results establish a framework for understanding meningioma biology, and provide preclinical rationale for new therapies to treat meningioma patients.

Previous page 1 2 3 4 5 6 7 8 . . . 33 Next page

PanLingua

News