tbuckley/cabot-search huggingface dataset:
Induction TPF followed by chemoradiation or radiotherapy-cetuximab in nonresectable advanced head and neck squamous cell carcinoma: A retrospective study in 164 patients.
Authors: Delphine Borchiellini, Charlotte Dupuis, Jocelyn Gal, Benjamin Lallemant, Marc Alfonsi, Karen Benezery, Christian Righini, Bruno Guelfucci, Michel Beltran, Alexandre Bozec, Gilles Poissonnet, Olivier Dassonville, Antoine Giovanni, Francois Morvan, Frederic Peyrade
Journal: Journal of Clinical Oncology (2012)

e16044 Background: Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced head and neck squamous cell carcinoma (LASCC). Radiotherapy (RT) associated with cetuximab (RT-cetux) is superior to RT alone and has less systemic toxicity than CRT. Recent data suggest RT-cetux could be an alternative treatment to CRT after induction TPF. The aim of this study was to report the outcome of these pts in clinical practice. Methods: A multicentric retrospective analysis was conducted in LASCC pts treated with induction TPF (T 75mg/m 2 day 1, P 75mg/m 2 day 1, F 750mg/m 2 /d day 1 to 4 – q3w), followed by CRT (cisplatin 100mg/m 2 – q3w) or RT-cetux (400mg/m 2 loading dose and 250mg/m 2 – q1w). Exploratory endpoints were progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Results: 164 pts treated from October 2005 to June 2010 were eligible. 113 pts had TPF followed by CRT and 51 pts had TPF followed by RT-cetux. Clinical characteristics were similar in each group, regarding gender (men 84% vs 92%), mean age (56 vs 57 yrs), BMI (23.4 vs 23 kg/m 2 ), alcohol consumption under treatment (41% vs 49%), non laryngeal tumor site (77% vs 73%), T3-T4 tumor size (84% vs 80%) and N+ status (71% vs 77%). There was a difference in performance status 0 and 1 between pts in CRT group (73% and 26%) and RT-cetux group (47% and 51%) (p=0.005). 2-yr PFS rate was 68% in CRT group vs 42% in RT-cetux group (p=0.002). After a median follow-up of 23 months, the median PFS was not reached in CRT pts vs 13 months (95% CI : 8.1-17.9 months) for RT-cetux group. At 2 years, CSS and OS rate was 84% and 78% vs 54% and 50%, respectively (p&lt;0.0001). Median CSS ans OS were not reached in CRT group as compared to 25 months (95% CI : 14.6-35.4 months) and 23 months (95% CI : 10.7-35.3 months) in the RT-cetux group, respectively. Conclusions: In daily practice, outcome after induction TPF for LASCC pts seems to be superior with standard CRT than RT-cetux. The higher proportion of PS 1 pts in the RT-cetux group could explain this difference. These data suggest that selection of pts should be carefully considered.
Introduction of Chromosomal Translocation t(11; 14) and a p53 Deletion into Normal B Cell-Derived iPSCs to Elucidate the Cellular Origin of Myeloma Cells
Authors: Aki Yanagi, Naohiro Tsuyama, Misaki Sugai, Yu Abe, Yusuke Azami, Yukari Yanai, Akinobu Ota, Karnan Sivasundaram, Moe Muramatsu, Tomonari Shigemura, Megumi Sasatani, Yuko Hashimoto, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai
Journal: Blood (2019)
Separate Roles of Asparagine and Glutamine in Cytostatic Effect of L-Asparaginase - Stable Isotope Tracing Approach
Authors: Katerina Hlozkova, Alpesh Thakker, Natividad Alquézar-Artieda, Marketa Zaliova, Jan Trka, Daniel A Tennant, Julia Starkova
Journal: Blood (2019)
DNA Methylation As a Biomarker of Outcome in JMML: An International Effort Towards Clinical Implementation
Authors: Julia Meyer, Maximillian Schönung, Christian Flotho, Adam B. Olshen, Mark Hartmann, Christoph Plass, Yusuke Okuno, Yoshiyuki Takahashi, Norihiro Murakami, Manabu Wakamatsu, Mignon L. Loh, Charlotte M. Niemeyer, Hideki Muramatsu, Daniel B. Lipka, Elliot Stieglitz
Journal: Blood (2019)
ATIM-27. TUMOR MUTATIONAL BURDEN PREDICTS RESPONSE TO ONCOLYTIC POLIO/RHINOVIRUS RECOMBINANT (PVSRIPO) IN MALIGNANT GLIOMA PATIENTS: ASSESSMENT OF TRANSCRIPTIONAL AND IMMUNOLOGICAL CORRELATES
Authors: Matthias Gromeier, Michael Brown, Nike Beuabier, Hai Yan, Yiping He, Gao Zhang, Annick Desjardins, James Herndon, Dani Bolognesi, Allan Friedman, Henry Friedman, Frances McSherry, Xiang Lin, Zhi Wei, Smita Nair, Katherine Peters, Dina Randazzo, John Sampson, Roger McLendon, Darell Bigner, David Ashley
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The live attenuated oral poliovirus vaccine was modified to contain a heterologous internal ribosomal entry site stemming from human rhinovirus type 2, creating PVSRIPO. PVSRIPO recognizes CD155, an oncofetal cell adhesion molecule and tumor antigen widely expressed ectopically in malignancy. We have previously reported that deep sequencing of biopsy material obtained prior to PVSRIPO infusion confirmed that a very low mutational load is associated with longer survival. METHODS Patient tumor material from both phase I and 2 clinical trials was collected pre PVSRIPO. When available, post-treatment tissue from longitudinal samples were also collected. Tissue was subjected to RNA sequencing, histological analysis, and flow cytometry analysis. RNAseq analyses were performed comparing pre- and post- treatment expression profiles and computational predictions of tumor immune composition deciphered changes after PVSRIPO therapy. Histology and flow cytometry quantitated myeloid, CD8/4/regulatory T cell densities, and other immune cell types after treatment and compared to baseline tissue similarly analyzed to detect changes. RESULTS To date, analysis of phase 1 trial data has demonstrated a correlation between low TMB and increased markers of immunological gene expression profiles. This trend was not observed in TCGA samples that were almost exclusively primary GBM suggesting and interplay with prior therapy or evolution with recurrence. CONCLUSION Our findings presented here suggest that response to PVSRIPO therapy, and possibly that of other modalities engaging innate antiviral signatures in situ, may be dependent upon prevailing tumor microenvironment composition/status at the time of treatment.
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability
Authors: Viktoriya Dubrovskaya, Karen Tran, Gabriel Ozorowski, Javier Guenaga, Richard Wilson, Shridhar Bale, Christopher A. Cottrell, Hannah L. Turner, Gemma Seabright, Sijy O’Dell, Jonathan L. Torres, Lifei Yang, Yu Feng, Daniel P. Leaman, Néstor Vázquez Bernat, Tyler Liban, Mark Louder, Krisha McKee, Robert T. Bailer, Arlette Movsesyan, Nicole A. Doria-Rose, Marie Pancera, Gunilla B. Karlsson Hedestam, Michael B. Zwick, Max Crispin, John R. Mascola, Andrew B. Ward, Richard T. Wyatt
Journal: Immunity (2019)

The elicitation of broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer remains a major vaccine challenge. Most cross-conserved protein determinants are occluded by self-N-glycan shielding, limiting B cell recognition of the underlying polypeptide surface. The exceptions to the contiguous glycan shield include the conserved receptor CD4 binding site (CD4bs) and glycoprotein (gp)41 elements proximal to the furin cleavage site. Accordingly, we performed heterologous trimer-liposome prime:boosting in rabbits to drive B cells specific for cross-conserved sites. To preferentially expose the CD4bs to B cells, we eliminated proximal N-glycans while maintaining the native-like state of the cleavage-independent NFL trimers, followed by gradual N-glycan restoration coupled with heterologous boosting. This approach successfully elicited CD4bs-directed, cross-neutralizing Abs, including one targeting a unique glycan-protein epitope and a bNAb (87% breadth) directed to the gp120:gp41 interface, both resolved by high-resolution cryoelectron microscopy. This study provides proof-of-principle immunogenicity toward eliciting bNAbs by vaccination.
T Cell Determinants of Response and Resistance to PD-1 Blockade in Richter's Transformation
Authors: Erin Parry, Camilla K Lemvigh, Annabelle J Anandappa, Shuqiang Li, Lillian Werner, Ana Lako, Noelia Purroy, Satyen H Gohil, Giacomo Oliveira, Pavan Bachireddy, Teddy Huang, Ignaty Leshchiner, Aina Zurita Martinez, Lars Ronn Olsen, Kenneth Livak, Gad Getz, Donna S Neuberg, Scott J Rodig, William G. Wierda, Peter Kharchenko, Nitin Jain, Catherine J. Wu
Journal: Blood (2019)
Sparing of the Lower Gastrointestinal Tract Microbiota Is Associated with Reduced Acute Graft-Versus-Host Disease
Authors: Doris M Ponce, Marina D Burgos da Silva, Antonio L.C. Gomes, Gillian Moore, John B. Slingerland, Eric G. Pamer, Ying Taur, Jonathan U. Peled, Marcel R.M. van den Brink
Journal: Blood (2019)
Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity
Authors: Lyra O. Randzavola, Katharina Strege, Marie Juzans, Yukako Asano, Jane C. Stinchcombe, Christian M. Gawden-Bone, Matthew N.J. Seaman, Taco W. Kuijpers, Gillian M. Griffiths
Journal: Journal of Clinical Investigation (2019)

CD8 cytotoxic T lymphocytes (CTLs) rely on rapid reorganization of the branched F-actin network to drive the polarized secretion of lytic granules, initiating target cell death during the adaptive immune response. Branched F-actin is generated by the nucleation factor actin-related protein 2/3 (Arp2/3) complex. Patients with mutations in the actin-related protein complex 1B (ARPC1B) subunit of Arp2/3 show combined immunodeficiency, with symptoms of immune dysregulation, including recurrent viral infections and reduced CD8+ T cell count. Here, we show that loss of ARPC1B led to loss of CTL cytotoxicity, with the defect arising at 2 different levels. First, ARPC1B is required for lamellipodia formation, cell migration, and actin reorganization across the immune synapse. Second, we found that ARPC1B is indispensable for the maintenance of TCR, CD8, and GLUT1 membrane proteins at the plasma membrane of CTLs, as recycling via the retromer and WASH complexes was impaired in the absence of ARPC1B. Loss of TCR, CD8, and GLUT1 gave rise to defects in T cell signaling and proliferation upon antigen stimulation of ARPC1B-deficient CTLs, leading to a progressive loss of CD8+ T cells. This triggered an activation-induced immunodeficiency of CTL activity in ARPC1B-deficient patients, which could explain the susceptibility to severe and prolonged viral infections.
Identifying Patterns of Inappropriate Plasma Transfusion Practices Using a Novel Multicenter Electronic Data Audit: Over 80 Percent of Plasma Transfused Is Inappropriate
Authors: Leigh Minuk, Jeannie Callum, Alan T. Tinmouth, Robert Skeate, Nancy Heddle, Donald M. Arnold, Troy Thompson, Ziad Sohl, Nadine Shehata, Cyrus C. Hsia, Rebecca Barty, Yang Liu
Journal: Blood (2019)
NCMP-08. CLINICAL FEATURES OF CAR T-CELL THERAPY NEUROTOXICITY AS POTENTIAL SURROGATE MARKERS FOR PROGRESSION AND OUTCOME
Authors: Carlen Yuen, Andrew Artz, Thomas Kelly, Shasha Wu, Anthony Reder, Kourosh Rezania, Betty Soliven, Tao Xie, James Mastrianni, Deric Park, Satyajit Kosuri, Peter Riedell, Wesley Klejch, Saad Ali, Michael Bishop
Journal: Neuro-Oncology (2019)

Abstract CAR T-cell therapy related neurotoxicity (NT) is common and can lead to fatalities. Early recognition may improve its management and treatment. METHODS Twenty-six patients with relapsed/refractory diffuse large B cell lymphoma who received commercial CAR T-cell therapy (25 axicabtagene ciloleucel [Yescarta®], 1 tisagenlecleucel [Kymriah®]) between December 2017 and September 2018 were assessed for NT based on CARTOX-10 score and Common Terminology Criteria for Adverse Events (CTCAE) version 4. RESULTS Twenty-three of 26 (88%) of patients developed NT, which was severe (Grade III-IV) in 8/26 (31%). Severe NT was associated with complete remission compared to progressive disease by both CTCAE (2.4 ±1.1 vs. 1.4 ± 1.3, p = 0.050) and CARTOX-10 score (8.3 ± 1.6 vs. 9.4 ± 1.5, p = 0.040). CARTOX-10 scores were lower for those transferred to the ICU compared to those transferred, respectively, on Days 8 (2.71 ± 4.78 vs. 9.28 ± 2.31, p = 0.010), 9 (2.71 ± 3.96 vs. 9.06 ± 2.50, p = 0.003) and 10 (2.86 ± 4.27 vs. 8.83 ± 3.37, p = 0.002). Depression was associated with poor overall survival (deceased 67% vs. alive 20%, p = 0.00004) and severe NT (severe NT 63% vs. non-severe NT 20%, p = 0.040). EEG findings of frontal intermittent rhythmic delta activity (FIRDA) in 22% (2/9) and triphasic waves in 33% (3/9) were exclusive found in severe NT. Tremulousness was present in 100% of severe NT compared to 67% of non-severe NT patients (p = 0.060). Delirium occurred in 2 patients, both of whom expired with severe NT. CONCLUSION Depression, tremor, delirium, encephalopathy, and EEG features of FIRDA and triphasic waves may represent early clinical signs that predict the development of severe NT in off-protocol CAR T-cell therapy. Paradoxically, severe NT is positively correlated with progression free survival and may indicate effective therapeutic response.
Physicians' and Patients' Perspectives on Treatments in ITP - a Multi-Country Perspective: Results from the ITP World Impact Survey (I-WISh)
Authors: James B. Bussel, Waleed Ghanima, Yoshiaki Tomiyama, Donald M. Arnold, Drew Provan, Ming Hou, Cristina Santoro, Serge Laborde, Alexandra Kruse, Caroline Kruse, Mervyn Morgan, Barbara Lovrencic, John Waller, Jens Haenig, Nichola Cooper
Journal: Blood (2019)
Targeted-Capture Sequencing Is a Useful Method for MRD Markers Screening in KMT2A (MLL) Rearranged Leukemia
Authors: Masashi Sanada, Tomomi Yamada, Yuka Iijima-Yamashita, Dai Nishijima, Takashi Kanamori, Daisuke Tomizawa, Toshinori Hori, Keizo Horibe
Journal: Blood (2019)
Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population‐based sample
Authors: Annemarie G. Hirsch, Cara Nordberg, Karen Bandeen‐Roche, Bruce K. Tan, Robert P. Schleimer, Robert C. Kern, Agnes Sundaresan, Jayant M. Pinto, Thomas L. Kennedy, Joseph Scott Greene, Jordan R. Kuiper, Brian S. Schwartz
Journal: Allergy (2019)

Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings.To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample.We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS ) was based on guideline criteria, and objective radiologic inflammation (CRSO ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRSS+O . Using weighted analysis, we calculated estimates for the source population.The proportion of women with L-M scores ≥ 3, 4, or 6 (CRSO ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses.In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O .
Impact of Neurocognitive Dysfunction in a Veteran Population Undergoing First Outpatient Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma
Authors: Shakira J. Grant, Lindsay M. Hannan, Jessica L. Brand, Robert E. Richard, Daniel Y. Wu, Solomon A. Graf, Jonathan Grim, Nicholas Burwick, Thomas R. Chauncey
Journal: Blood (2019)
Rare Germline Mutations in Complement Regulatory Genes Make the Antiphospholipid Syndrome Catastrophic
Authors: Shruti Chaturvedi, Evan M Braunstein, Xuan Yuan, Hang Chen, Ravi Kumar Alluri, Michael B. Streiff, Michelle Petri, Mark Crowther, Keith R McCrae, Robert A. Brodsky
Journal: Blood (2019)
Pharmacological Perturbation of the Immunoproteasome in Hematologic Neoplasias: Therapeutic Implications
Authors: Sondra L. Downey-Kopyscinski, Ricardo De Matos Simoes, Megan Bariteau, Minasri L. Borah, Sam Bender, Janaka Foneska, Jennifer Roth, Richard Groen, Gina Walter, Manja Friese-Hamim, Samantha M. Goodstal, Michael Sanderson, Constantine S. Mitsiades
Journal: Blood (2019)
Incidence and Predictors of Respiratory Viral Infections By Multi-Plex PCR in Allogeneic Hematopoietic Cell Transplant (HCT) Recipients 50 Years and Older Including Geriatric Assessment (GA)
Authors: Christopher R D'Angelo, Masha Kocherginsky, Michael R Bishop, Lucy A Godley, Justin Kline, Richard A. Larson, Hongtao Liu, Olatoyosi Odenike, Jennifer Pisano, Wendy Stock, Andrew Artz
Journal: Blood (2014)
Next Generation Sequencing May be Helpful in Designing Novel Combinations Among Heavily Pretreated Myeloma Patients, Refractory to All Available Approved Anti-Myeloma Drugs
Authors: Guldane Cengiz Seval, Isinsu Kuzu, Seher Yuksel, Gulsah Kaygusuz, Klara Dalva, Muhit Ozcan, Meral Beksac
Journal: Blood (2019)
CMET-19. QUESTIONING THE PARADIGM: DO CSF CYTOLOGY AND MRI SCANNING IDENTIFY THE SAME DISEASE IN PATIENTS WITH NEOPLASTIC MENINGITIS (NM) – DATA FROM AN INTERNATIONAL NM REGISTRY AND A META-ANALYSIS
Authors: Christopher Messner, Morris Groves, Silvia Hofer, David Roberge, Dawit Aregawi, Suriya Jeyapalan, Roberta Rudà, Michael Glantz
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION CSF cytology and neuraxis MRI scanning are complementary examinations for diagnosing NM. Positive cytology is the current gold standard despite relatively low sensitivity. Although MRI is an accepted alternative diagnostic tool for both treatment and clinical trial inclusion, its sensitivity and specificity are poorly understood. METHODS We conducted an exhaustive, PRISMA-compliant systematic review of the literature from January 1990 to September 2016 comparing MRI to CSF cytology (the gold standard) for the diagnosis of NM. Relevant studies were assigned a level of evidence using AAN criteria. Pre-specified data was extracted, and summary statistics were calculated using the inverse variance method and random effects model. Survival of patients diagnosed with various combinations of CSF cytology and MRI was also extracted and summary statistics were calculated. RESULTS Thirteen studies (2 class-I, 5 class-II, 5 class-III, 1 class-IV, 1646 solid and hematologic tumor patients) provided data sufficient to calculate the diagnostic characteristics of MRI. Sensitivity and specificity were low (63.4% [56.5–71.2] and 40.1% [30.2–53.1] respectively). False positive and false negative rates were high (59.9% [46.9–69.8] and 36.6% [28.8–43.5] respectively). Various sensitivity analyses (recent studies, class I/II studies, only class I studies, specific tumor histologies) yielded very similar results. Overall survival in patients with MRI (+)/CSF (+), MRI (+)/CSF (-), and MRI (-)/CSF (+) disease (3 studies, 347 patients) were 50.8 [39.8–64.8], 115.4 [70.4–189.4] and 228.7 [130.5–400.7] days respectively (p &lt; 0.001). CONCLUSIONS MRI scanning can diagnose leptomeningeal metastases, but is a very poor surrogate for CSF cytology. Patients with NM diagnosed by various combinations CSF cytology and MRI positivity have dramatically different survivals, suggesting that these categories define subsets of patients with NM with different natural histories. This finding has important implications for patient care and clinical trial design and interpretation. Novel diagnostic strategies for NM should be subjected to similar analysis.
Dynamics of Activated CD8+ T-cells and Decreased Osteoclasts in the Tumor Microenvironment are Associated with Clinical Efficacy of Anti-PD-L1 and Anti-CD38 Combination Treatment in Relapsed or Refractory Multiple Myeloma
Authors: Aparna Raval, Hearn Jay Cho, Cherie Green, Elisabeth Wassner Fritsch, Connie Ma, Naomi Chang, Mark Yan, Mark Kockx, Shine Shen, Ling-Yuh Huw, Emily Balestiere, Marina Lipkind, Huang Huang, Michelle Byrtek, Dawn Colburn, Sandy W. Wong, Jeffrey M. Venstrom, Joanne I Adamkewicz
Journal: Blood (2019)
Long-Term Proteasome Inhibitor (PI) Therapy in Community Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Transitioning from Bortezomib (Btz)-Based to Ixazomib-Based Induction: Results from the US MM-6 Study in the Real World (RW) Setting
Authors: Robert M. Rifkin, Sudhir Manda, Stephen J Noga, Habte A Yimer, Saulius K. Girnius, Ruemu Ejedafeta Birhiray, Christopher A. Yasenchak, Roger M. Lyons, Presley Whidden, Robert L. Schlossman, Bingxia Wang, Ralph V. Boccia
Journal: Blood (2019)
Presenting symptoms of cancer and stage at diagnosis: evidence from a cross-sectional, population-based study
Authors: Minjoung Monica Koo, Ruth Swann, Sean McPhail, Gary A Abel, Lucy Elliss-Brookes, Greg P Rubin, Georgios Lyratzopoulos
Journal: The Lancet Oncology (2019)

BackgroundEarly diagnosis interventions such as symptom awareness campaigns increasingly form part of global cancer control strategies. However, these strategies will have little impact in improving cancer outcomes if the targeted symptoms represent advanced stage of disease. Therefore, we aimed to examine associations between common presenting symptoms of cancer and stage at diagnosis.MethodsIn this cross-sectional study, we analysed population-level data from the English National Cancer Diagnosis Audit 2014 for patients aged 25 years and older with one of 12 types of solid tumours (bladder, breast, colon, endometrial, laryngeal, lung, melanoma, oral or oropharyngeal, ovarian, prostate, rectal, and renal cancer). We considered 20 common presenting symptoms and examined their associations with stage at diagnosis (TNM stage IV vs stage I–III) using logistic regression. For each symptom, we estimated these associations when reported as a single presenting symptom and when reported together with other symptoms.FindingsWe analysed data for 7997 patients. The proportion of patients diagnosed with stage IV cancer varied substantially by presenting symptom, from 1% (95% CI 1–3; eight of 584 patients) for abnormal mole to 80% (71–87; 84 of 105 patients) for neck lump. Three of the examined symptoms (neck lump, chest pain, and back pain) were consistently associated with increased odds of stage IV cancer, whether reported alone or with other symptoms, whereas the opposite was true for abnormal mole, breast lump, postmenopausal bleeding, and rectal bleeding. For 13 of the 20 symptoms (abnormal mole, breast lump, post-menopausal bleeding, rectal bleeding, lower urinary tract symptoms, haematuria, change in bowel habit, hoarseness, fatigue, abdominal pain, lower abdominal pain, weight loss, and the "any other symptom" category), more than 50% of patients were diagnosed at stages other than stage IV; for 19 of the 20 studied symptoms (all except for neck lump), more than a third of patients were diagnosed at stages other than stage IV.InterpretationDespite specific presenting symptoms being more strongly associated with advanced stage at diagnosis than others, for most symptoms, large proportions of patients are diagnosed at stages other than stage IV. These findings provide support for early diagnosis interventions targeting common cancer symptoms, countering concerns that they might be simply expediting the detection of advanced stage disease.FundingUK Department of Health's Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis; and Cancer Research UK.