bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma
Authors: Berger Barry M. , Hanna Glenn J. , Posner Marshall R. , Genden Eric M. , Lautersztain Julio , Naber Stephen P. , Del Vecchio Fitz Catherine , Kuperwasser Charlotte 
Published: May 2022

Abstract

Purpose:
Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine posttreatment surveillance among a large population of real-world patients.

Experimental Design:
This retrospective clinical case series included 1,076 consecutive patients across 108 U.S. sites who were ≥ 3 months posttreatment for HPV-driven OPSCC and who had one or more TTMV-HPV DNA tests (NavDx, Naveris Laboratories) obtained during surveillance between February 6, 2020, and June 29, 2021. Test results were compared with subsequent clinical evaluations.

Results:
Circulating TTMV-HPV DNA was positive in 80 of 1,076 (7.4%) patients, with follow-up available on all. At first positive surveillance testing, 21 of 80 (26%) patients had known recurrence while 59 of 80 (74%) patients were not known to have recurrent disease. Among these 59 patients, 55 (93%) subsequently had a confirmed recurrence, 2 patients had clinically suspicious lesions, and 2 had clinically “no evidence of disease” (NED) at last follow-up. To date, the overall positive predictive value of TTMV-HPV DNA testing for recurrent disease is 95% (N = 76/80). In addition, the point-in-time negative predictive value is 95% (N = 1,198/1,256).

Conclusions:
These findings highlight the clinical potential for circulating TTMV-HPV DNA testing in routine practice. As a surveillance tool, TTMV-HPV DNA positivity was the first indication of recurrence in the majority of cases, pre-dating identification by routine clinical and imaging exams. These data may inform future clinical and guideline-endorsed strategies for HPV-driven malignancy surveillance.
See related commentary by Colevas, p. 4171
PD-1 Inhibition—Trouble for Subsequent TIL Therapy in Patients with Melanoma?
Authors: Blass Eryn , Ott Patrick A. 
Published: May 2022

SummaryTo explore the lower efficacy of adoptive cell transfer (ACT) therapy in patients with anti–PD-1 experienced melanoma, tumor mutational burden (TMB), predicted neoantigen frequencies, and tumor-infiltrating lymphocyte (TIL) neoantigen reactivity were assessed. Reduced neoantigen-specific TIL frequencies correlated with lower ACT response even in patients with similar TMB, suggesting a potentially harmful effect of PD-1 inhibition on T-cell outgrowth.See related article by Levi et al., p. 3042
Abstract A012: Advanced melanoma exhibits a diversity of evolutionary routes to lethality
Authors: Coulton Alexander , Lobon Irene , Spain Lavinia , Rowan Andrew , Shnidrig Desiree , Shepherd Scott , Shum Ben , Byrne Fiona , Au Lewis , Edmonds Kim , Carlyle Ellie , Renn Alexandra , Messiou Christina , Spencer Charlotte , Schmidt Andreas M. , Tippu Zayd , Rogiers Aljosja , Emmerich Max , Gerard Camille , Pallikonda Husayn , Naceur-Lombardelli Cristina , Foijer Floris , van den Bos Hilda , Wardenaar René , Spierings Diana , Young Kate , Pickering Lisa , Furness Andrew , Borg Elaine , Mitchison Miriam , Moore David , Falzon Mary , Proctor Ian , Stewart Ruby , Mahadeva Ula , Green Anna , Larkin James , Swanton Charles , Jamal-Hanjani Mariam , Litchfield Kevin , Turajlic Samra 
Published: May 2022

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR002) of the Conference Proceedings.
Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A012.
Abstract A016: Mapping of subclonal events in multi-region multi-omics oncogenomics studies
Authors: Tran Mark , McGranahan Nicholas , Barnes Chris , Herrero Javier 
Published: May 2022

Abstract
Advanced cancer genomics relies on multi-region sequencing to detect intra-tumor heterogeneity. These data allow for backtracking tumor’s evolutionary history by inferring its clonal population structure (Roth et al. 2014) and reconstructing a phylogenetic tree (Malikic et al. 2015). However, methods for mapping subclonal copy number changes onto tumor evolutionary trees are still lacking. McGranahan et al. 2017 presented LOHHLA, a tool for estimation of allele-specific HLA loss from sequencing data, which demonstrated the effects of loss of heterozygosity of HLA on early-stage non-small-cell lung cancer. Here, we present MAPping SubClonal Events (MAPSCE), a tool for mapping subclonal copy number events on the tumor evolutionary trees. Similar to LOHHLA, MAPSCE uses Quadratic Programming for the branch test, where copy-number states before and after a branch are estimated, one branch at a time. Additionally, it relies on the Bayesian Information Criterion from bootstrapped samples to compare the results for each branch and the null hypothesis (H0 = no subclonal event). While mapping loss of heterozygosity events of HLA allele in TRACERx 100 cohort (Jamal-Hanjani et al. 2017) MAPSCE pre-empts the need for manual review on LOHHLA’s initial results, can take into account multiple possible solutions and maintains high accuracy of the results. Using simulated data sets we tested the robustness of MAPSCE to the addition of noise to the cluster CCFs that define each tumor clone. MAPSCE outperforms LOHHLA’s mapping of subclonal LOH events when adding noise up to ±25% CCF. Sub-clonal LOH affecting larger clones are easier to detect and both LOHHLA and MAPSCE produce similar results. However, only MAPSCE maintains high accuracy in detecting events affection smaller clones. In data sets with simulated amplification and duplication events, MAPSCE can also identify duplication and amplification events with at least 70% accuracy up to ±20% CCF noise range. In the future, we are planning to extend this approach to other data types such as gene expression and methylation data, a combination of which would allow us to identify the biological events underlying the formation of new tumor clones, to ultimately integrate these in a comprehensive model of cancer evolution.
Citation Format: Mark Tran, Nicholas McGranahan, Chris Barnes, Javier Herrero. Mapping of subclonal events in multi-region multi-omics oncogenomics studies [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A016.
Abstract A017: In vivo tracking of clonal dynamics during UV-induced skin carcinogenesis
Authors: Avdieiev Stanislav , Tordesillas Leticia , Chiang Omar Chavez , Chen Zhihua , Simoes Luiza Silva , Chen Y. Ann , Andor Noemi , Gatenby Robert , Flores Elsa R. , Brown Joel S. , Tsai Kenneth Y. 
Published: May 2022

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR004) of the Conference Proceedings.
Citation Format: Stanislav Avdieiev, Leticia Tordesillas, Omar Chavez Chiang, Zhihua Chen, Luiza Silva Simoes, Y. Ann Chen, Noemi Andor, Robert Gatenby, Elsa R. Flores, Joel S. Brown, Kenneth Y. Tsai. In vivo tracking of clonal dynamics during UV-induced skin carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A017.
Abstract A022: Effects of chemotherapy on the peripheral immune-cellome in patients with pancreatic cancer
Authors: Svensson Maja , Petersson Alexandra , Sincic Viktor , Hau Sofie Olsson , Eberhard Jakob , Nord David Gisselsson , Leandersson Karin , Lundberg Kristina , Jirström Karin 
Published: May 2022

Abstract
Pancreatic cancer (PC) has become one of the leading causes of cancer related deaths. Late detection and resistance to therapy are two reasons for the dismal prognosis of this disease. Hence, there is an immense need for novel treatment options as well as predictive biomarkers, to prolong the life of these patients. The Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer, the CHAMP study (clinical trial nr NCT03724994), is an ongoing observational, prospective clinical study that includes newly diagnosed patients with PC or other periampullary cancers receiving adjuvant or first-line palliative chemotherapy. The present study aims to investigate the peripheral immune-cellome in serial blood samples obtained during treatment from 24 patients, of whom 8 had resectable tumors. Buffy coat was isolated from blood samples taken at baseline (before treatment), after one month and after three to four months of treatment. Flow cytometry with two panels of antibodies was applied to detect major immune populations in both the innate and the adaptive immune system, as well as subpopulations of T cells. Immune cell frequencies were compared between patients with progression and no progression during treatment, and the associations of different immune cell subsets with overall survival were examined. As B cells have been highlighted as being of particular clinical relevance, single-cell transcriptomics and proteomics will be applied to further delineate the dynamics and prognostic impact of individual subtypes within this lineage. The results will provide important real-world data on the longitudinal dynamics of circulating immune cells under the pressure of chemotherapy in patients with PC. These results will in the future be related to analyses of circulating tumor DNA in matched blood samples, and together they will provide a foundation for forthcoming adaptive treatment trials based on results from the CHAMP study.
Citation Format: Maja Svensson, Alexandra Petersson, Viktor Sincic, Sofie Olsson Hau, Jakob Eberhard, David Gisselsson Nord, Karin Leandersson, Kristina Lundberg, Karin Jirström. Effects of chemotherapy on the peripheral immune-cellome in patients with pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A022.
Abstract A025: Agency of the Cell: Convergence between Origin of Life, Evolution, Cognition and Cancer
Authors: Marshall Perry S. 
Published: May 2022

Abstract
All cells exhibit agency and evolve purposefully. This is why cancer has outwitted doctors for 100 years and why Stage 3-4 patients are no better in 2022 than in 1930. Evolution was presumed to be random and purposeless, yet all cells possess cognition (Shapiro 2020). Cell behavior is normally algorithmic, but uniquely responds to novel situations. This is what makes evolution (and cancer) possible. Cognition—sensing and responding to the environment—is the unifying principle behind the genetic code, origin of life, evolution, consciousness, artificial intelligence, and cancer. Thus the central question in biology is: What is the nature and origin of cognition? A solution to the origin of the genetic code, for which the presenter’s organization offers a $10 million prize (announced at the Royal Society in 2019) is an unsolved cognition problem. This choice is a non-deterministic action of a free agent with sensory capacity and memory. It is not computable from prior states. As well as reading and reacting to its environment, it anticipates future threats, chooses goals and reasons inductively. Computers do none of these things. This new model explains the futility of reducing cancer to a single random or algorithmic component, and suggests we should treat cancer as an autonomous purposeful agent with unique identity and capacity to choose.
Citation Format: Perry S. Marshall. Agency of the Cell: Convergence between Origin of Life, Evolution, Cognition and Cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A025.
Abstract A032: Integrating spatial analysis and agent-based modeling for studies of stroma sheltering effects in NSCLC
Authors: Miti Tatiana , Miller Anna , Myroshnychenko Daria , Desai Bina , Marusyk Andriy , Basanta David 
Published: May 2022

Abstract
Background: Stroma plays a crucial role in shaping tumor growth dynamics, invasion, and metastasis. High stroma to tumor ratio in the clinic is associated with poor outcomes and shorter remission periods for lung cancer patients. Recent studies suggest that stroma shelters tumor cells during drug administration, but the precise mechanisms to confer this protection remain unclear. We hypothesize that stroma secretes paracrine factors that enhance tumor cells' proliferation rate in proximity, hence outcompeting the death rate due to therapies. In this context, the residual disease is an inherent stage in tumors' eco-evolutionary dynamics under treatment. Therefore, understanding the nature of stroma-tumor cell interactions is crucial for designing effective therapies. Methods: The spatial relationship between the stroma and proliferating tumor cells was interrogated via spatial analysis of 2D samples from mouse xenograft models and subsequent spatial agent-based modeling (ABM). Results: First, we built a pipeline to quantify the spatial extent and amplitude of stroma shielding the presence or absence of treatment. The spatial distributions of tumor cells, their proliferating rates, and the spatial extent of stroma protective effects are used to parametrize the ABM and simulate the spatio-temporal dynamics of tumor growth with and without treatment. Our preliminary results show moderately higher clustering of proliferating and stroma cells than stroma and non-proliferating cells or random distribution in the absence of treatment. In contrast, during therapy, stroma-proliferating tumor cell clustering is considerably higher than stroma-non proliferating tumor cells and stroma-random distribution. Moreover, stroma's protective effect during treatment seems limited to cells either in direct contact with stromal cells or in their immediate proximity. Conclusions: We expect our results to lead to novel therapeutic interventions that aim to shift eco-evolutionary dynamics rather than maximize short-term tumor cell killing efficiency.
Citation Format: Tatiana Miti, Anna Miller, Daria Myroshnychenko, Bina Desai, Andriy Marusyk, David Basanta. Integrating spatial analysis and agent-based modeling for studies of stroma sheltering effects in NSCLC [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A032.
Abstract B011: P300 histone acetyltransferase mediates glioma stem cell adaptive response to therapeutic stress
Authors: Muthukrishnan Sree Deepthi , Kawaguchi Riki , Nair Pooja , Alvarado Alvaro , Kornblum Harley 
Published: May 2022

Abstract
Glioma stem-like and tumor cells exhibit phenotypic plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. In this study, we employed single-cell and whole transcriptomic analyses to uncover that radiation-stress induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular gene regions allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity using a small molecule inhibitor C646 or gene knockdown reverses the epigenetic changes induced by radiation, inhibits the adaptive conversion of GSC into vascular-like cells, reduces tumor growth and enhances animal survival. Our findings highlight an important role for P300 in mediating adaptive response of glioma stem cells to therapeutic-stress, and opens a new therapeutic avenue for preventing glioma recurrence.
Citation Format: Sree Deepthi Muthukrishnan, Riki Kawaguchi, Pooja Nair, Alvaro Alvarado, Harley Kornblum. P300 histone acetyltransferase mediates glioma stem cell adaptive response to therapeutic stress [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B011.
Abstract B013: Dissecting cell states that enable multi-stressor resistance in cancer
Authors: Schaff Dylan L. , Fasse Aria J. , Shaffer Sydney M. 
Published: May 2022

Abstract
In this work, we investigate how single-cell differences in melanoma lead to resistance to multiple diverse and therapeutically relevant stressors. Targeted small-molecule inhibitors and immunotherapy have shown incredible success in the clinic. However, most patients still only partially respond to a given treatment, succumbing to recurrent, treatment-resistant tumors. As a result, oncologists must resort to sequentially treating tumors with new drugs or co-treating with multiple drugs from the beginning. Despite such a complex clinical paradigm, researchers are still studying the root of treatment resistance one drug at a time. We believe that by more broadly studying how certain cells adapt to and survive a multitude of stressful conditions, we can identify treatment strategies that more effectively overcome many resistant behaviors at once. Here, we use lentiviral cell barcoding to simultaneously trace cells that survive stress from microenvironmental factors (extracellular acidosis and hypoxia), inhibition of specific signaling pathways (with Dabrafenib and Trametinib), and chemotherapy (Cisplatin and Doxorubicin) back to their cells of origin and characterize them by scRNA-seq. Strikingly, we have found that there is a rare population of stress-naïve cells that is resistant to our entire panel of stressors. We are exploring two complementary approaches for overcoming this multi-stressor resistance. First, we have combined cell barcoding and scRNA-seq to identify the initial differences in gene expression that allow certain lineages of cells to survive across stressful conditions. Our goal is to use small-molecule inhibitors and genetic knockouts to target these differences in gene expression in stress-naïve cells, eliminating multi-stressor resistance at its source. Second, we are tracking lineages of cells as they undergo a series of cellular changes needed to ultimately survive our panel of stressors. Using scRNA-seq and cell barcoding, we are identifying these crucial changes as cells reprogram into full resistance. We will look to prevent this reprogramming by simultaneously stressing cells and targeting core reprogramming genes and pathways. Overall, this work uncovers single-cell gene expression differences that allow cancer cells to survive under many stressful conditions. We will work to overcome this resistance by directly eliminating the multi-stressor resistant cells and disrupting their ability to reprogram.
Citation Format: Dylan L. Schaff, Aria J. Fasse, Sydney M. Shaffer. Dissecting cell states that enable multi-stressor resistance in cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B013.
Abstract B017: Homotypic cell-cell fusion in TNBC cells downregulates cancer testis antigen MAGEC2 and increases therapeutic sensitivity to paclitaxel and doxorubicin
Authors: Gardner Andrea , Zheng Lan , Howland Kennedy , Iloegbunam Chisom , Barrera Patrik , De Santiago Carolina , Brock Amy 
Published: May 2022

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR007) of the Conference Proceedings.
Citation Format: Andrea Gardner, Lan Zheng, Kennedy Howland, Chisom Iloegbunam, Patrik Barrera, Carolina De Santiago, Amy Brock. Homotypic cell-cell fusion in TNBC cells downregulates cancer testis antigen MAGEC2 and increases therapeutic sensitivity to paclitaxel and doxorubicin [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B017.