This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from October 1 through October 15.
If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing ericd_schuller@dfci.harvard.edu.
For more about Dana-Farber science, tune in to our Unraveled podcast, available at dana-farber.org/unraveled, or wherever you get your podcasts.
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Annals of Oncology
Circulating Tumor DNA Association with Residual Cancer Burden After Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer in TBCRC 030
Parsons HA, Blewett T, Chu X, Sridhar S, Santos K, Xiong K, Patel A, Cheng J, Rhoades J, Liu R, Burstein HJ, Winer EP, Tayob N, Krop IE, Makrigiorgos GM, Golub TR, Mayer EL, Adalsteinsson VA
BACKGROUND: We aimed to examine circulating tumor DNA (ctDNA) and its association with residual cancer burden (RCB) using an ultrasensitive assay in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant chemotherapy.
PATIENTS AND METHODS: We identified responders (RCB 0/1) and matched non-responders (RCB 2/3) from the phase II TBCRC 030 prospective study of neoadjuvant paclitaxel versus cisplatin in TNBC. We collected plasma samples at baseline, 3 weeks and 12 weeks (end of therapy). We created personalized ctDNA assays utilizing MAESTRO mutation enrichment sequencing. We explored associations between ctDNA and RCB status and disease recurrence.
RESULTS: Of 139 patients, 68 had complete samples and no additional neoadjuvant chemotherapy. Twenty-two were responders and 19 of those had sufficient tissue for whole-genome sequencing. We identified an additional 19 non-responders for a matched case-control analysis of 38 patients using a MAESTRO ctDNA assay tracking 319-1000 variants (median 1000 variants) to 114 plasma samples from 3 timepoints. Overall, ctDNA positivity was 100% at baseline, 79% at week 3 and 55% at week 12. Median tumor fraction (TFx) was 3.7 × 10-4 (range 7.9 × 10-7-4.9 × 10-1). TFx decreased 285-fold from baseline to week 3 in responders and 24-fold in non-responders. Week 12 ctDNA clearance correlated with RCB: clearance was observed in 10 of 11 patients with RCB 0, 3 of 8 with RCB 1, 4 of 15 with RCB 2 and 0 of 4 with RCB 3. Among six patients with known recurrence, five had persistent ctDNA at week 12.
CONCLUSIONS: Neoadjuvant chemotherapy for TNBC reduced ctDNA TFx by 285-fold in responders and 24-fold in non-responders. In 58% (22/38) of patients, ctDNA TFx dropped below the detection level of a commercially available test, emphasizing the need for sensitive tests. Additional studies will determine whether ctDNA-guided approaches can improve outcomes.
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Blood
DDX41: Here, There…And Everywhere
Reilly CR, Lane AA
In this issue of Blood, Cheloor Kovilakam et al report a comprehensive population-level analysis of >450 000 adults in the UK Biobank assessing the epidemiologic characteristics, clinical features, and malignancy risk associated with germ line pathogenic variants in the DEAD box RNA helicase 41 gene (DDX41-GPV).
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Blood
MYD88L265P Augments Proximal B-Cell Receptor Signaling in Large B-Cell Lymphomas Via an Interaction with DOCK8
Mandato E, Yan Q, Ouyang J, Paczkowska J, Qin Y, Hao Y, Bojarczuk K, Hansen J, Chapuy B,
Rodig SJ, Khan SJ, Redd RA, Shipp MA
Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease with at least 5 recognized molecular subtypes. Cluster 5 (C5)/MCD tumors frequently exhibit concurrent alterations in the toll-like receptor (TLR) and B-cell receptor (BCR) pathway members, MYD88L265P and CD79B, and have a less favorable prognosis. In healthy B cells, the synergy between TLR and BCR signaling pathways integrates innate and adaptive immune responses and augments downstream NF-κB activation. In addition, physiologic TLR9 pathway engagement via MYD88, protein tyrosine kinase 2 (PYK2), and dedicator of cytokinesis 8 (DOCK8) increases proximal BCR signaling in healthy murine B cells. Although C5/MCD DLBCLs are selectively sensitive to Bruton tyrosine kinase (BTK) inhibition in in vitro studies and certain clinical trials, the role of mutated MYD88 in proximal BCR signaling remains undefined. Using engineered DLBCL cell line models, we found that concurrent MYD88L265P and CD79B alterations significantly increased the magnitude and duration of proximal BCR signaling, at the level of spleen tyrosine kinase and BTK, and augmented PYK2-dependent DOCK8 phosphorylation. MYD88L265P DLBCLs have significantly increased colocalization of DOCK8 with both MYD88 and the proximal BCR-associated Src kinase, LYN, in comparison with MYD88WT DLBCLs, implicating DOCK8 in MYD88L265P/proximal BCR cross talk. Additionally, DOCK8 depletion selectively decreased proximal BCR signaling, cellular proliferation, and viability of DLBCLs with endogenous MYD88L265P/CD79BY196F alterations and increased the efficacy of BTK blockade in these lymphomas. Therefore, MYD88L265P/DOCK8-enhanced proximal BCR signaling is a likely mechanism for the increased sensitivity of C5/MCD DLBCLs to BTK blockade.
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Cancer Cell
Genetically Informed Therapy for Lymphoma: The Discomfiting Benefit of Lumping Splits
Hahn CK
Zhang et al. report a randomized phase 2 trial for diffuse large B cell lymphoma (DLBCL) that compared standard of care (R-CHOP) to R-CHOP combined with one of 5 agents matched to an individual lymphoma's genetics. Overall, the matching strategy significantly outperformed R-CHOP, laying the foundation for a paradigm-shifting phase 3 trial.
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Cancer Cell
ZNF683 Marks a CD8(+) T Cell Population Associated with Anti-Tumor Immunity Following Anti-PD-1 Therapy for Richter Syndrome
Parry EM, Lemvigh CK, Deng S, Dangle N, Ruthen N, Knisbacher BA, Li S, Zhang W, Johnson C,
Long JM, Yin S, Werner L, Anandappa A, Purroy N, Gohil S, Oliveira G, Huang T, Livak KJ, Getz G, Neuberg D, Kharchenko P, Wu CJ
Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells. This signature overlaps with that of tumor-infiltrating populations from anti-PD-1 responsive solid tumors. ZNF683 is found to directly target key T cell genes (TCF7, LMO2, CD69) and impact pathways of T cell cytotoxicity and activation. Analysis of pre-treatment peripheral blood from 10 independent patients with RS treated with anti-PD-1, as well as patients with solid tumors treated with anti-PD-1, supports an association of ZNF683high T cells with response.
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Gastroenterology
Transforming Growth Factor-β Blockade in Pancreatic Cancer Enhances Sensitivity to Combination Chemotherapy
Qiang L, Hoffman MT, Ali LR, Castillo JI, Kageler L, Temesgen A, Lenehan P, Wang SJ, Bello E,
Cardot-Ruffino V, Uribe GA, Yang A, Dougan M, Aguirre AJ, Raghavan S, Dougan SK
BACKGROUND & AIMS: Transforming growth factor-b (TGFb) plays pleiotropic roles in pancreatic cancer, including promoting metastasis, attenuating CD8 T-cell activation, and enhancing myofibroblast differentiation and deposition of extracellular matrix. However, single-agent TGFb inhibition has shown limited efficacy against pancreatic cancer in mice or humans.
METHODS: We evaluated the TGFβ-blocking antibody NIS793 in combination with gemcitabine/nanoparticle (albumin-bound)-paclitaxel or FOLFIRINOX (folinic acid [FOL], 5-fluorouracil [F], irinotecan [IRI] and oxaliplatin [OX]) in orthotopic pancreatic cancer models. Single-cell RNA sequencing and immunofluorescence were used to evaluate changes in tumor cell state and the tumor microenvironment.
RESULTS: Blockade of TGFβ with chemotherapy reduced tumor burden in poorly immunogenic pancreatic cancer, without affecting the metastatic rate of cancer cells. Efficacy of combination therapy was not dependent on CD8 T cells, because response to TGFβ blockade was preserved in CD8-depleted or recombination activating gene 2 (RAG2-/-) mice. TGFβ blockade decreased total α-smooth muscle actin-positive fibroblasts but had minimal effect on fibroblast heterogeneity. Bulk RNA sequencing on tumor cells sorted ex vivo revealed that tumor cells treated with TGFβ blockade adopted a classical lineage consistent with enhanced chemosensitivity, and immunofluorescence for cleaved caspase 3 confirmed that TGFβ blockade increased chemotherapy-induced cell death in vivo.
CONCLUSIONS: TGFβ regulates pancreatic cancer cell plasticity between classical and basal cell states. TGFβ blockade in orthotropic models of pancreatic cancer enhances sensitivity to chemotherapy by promoting a classical malignant cell state. This study provides scientific rationale for evaluation of NIS793 with FOLFIRINOX or gemcitabine/nanoparticle (albumin-bound) paclitaxel chemotherapy backbone in the clinical setting and supports the concept of manipulating cancer cell plasticity to increase the efficacy of combination therapy regimens.
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Journal of Clinical Oncology
Adolescent and Young Adult Germ Cell Tumors: Epidemiology, Genomics, Treatment, and Survivorship
Frazier AL
Innovations in the care of adolescent and young adult (AYA) germ cell tumors (GCTs) are needed for one of the most common AYA cancers for which treatment has not significantly changed for several decades. Testicular GCTs (TGCTs) are the most common cancers in 15- to 39-year-old men, and ovarian GCTs (OvGCTs) are the leading gynecologic malignancies in women younger than 25 years. Excellent outcomes, even in widely metastatic disease using cisplatin-based chemotherapy, can be achieved since Einhorn and Donohue's landmark 1977 study in TGCT. However, as the severity of accompanying late effects (ototoxicity, neurotoxicity, cardiovascular disease, second malignant neoplasms, nephrotoxicity, and others) has emerged, efforts to deintensity treatment and find alternatives to cisplatin have taken on new urgency. Current innovations include the collaborative design of clinical trials that accrue GCTs across all ages and both sexes, including adolescents (previously on pediatric trials), and OvGCT (previously on gynecologic-only trials). Joint trials accrue larger sample sizes at a faster rate and therefore evaluate new approaches more rapidly. These joint trials also allow for biospecimen collection to further probe GCT etiology and underlying mechanisms of tumor growth, thus providing new therapeutic options. This AYA approach has been fostered by The Malignant Germ Cell International Consortium, which includes over 115 GCT disease experts from pediatric, gynecologic, and genitourinary oncologies in 16 countries. Trials in development incorporate, to our knowledge, for the first time, molecular risk stratification and precision oncology approaches on the basis of specific GCT biology. This collaborative AYA approach pioneering successfully in GCT could serve as a model for impactful research for other AYA cancer types.
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Journal of Clinical Oncology
Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study
Versluis J, Tsai HK, Gibson CJ, Cutler C, Lindsley RC
PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study.
METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity).
RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P < .001). Among those with a TP53 mutation, OS was similar between TP53single versus TP53multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001).
CONCLUSION: HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.
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Journal of Clinical Oncology
Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial
Zhao F, Lee JW, Graham N, Gray R
PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation.
METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI).
RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89).
CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.
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Journal of Clinical Oncology
Reply to Z.R. McCaw et al
Matulonis UA
We thank McCaw et al for their thoughtful comments and interest in our study. We acknowledge that constructing a concurrent response curve over time to calculate a mean duration of response (DOR) can be one way to represent efficacy in an intent-to-treat population. Time-to-event analyses such as event-free survival and progression-free survival (PFS) are others that account for time on therapy for both responders and nonresponders. In the context of the single-arm SORAYA trial which tested the antibody-drug conjugate mirvetuximab soravtansine in patients with folate receptor alpha–positive platinum-resistant recurrent ovarian cancer, the efficacy and safety profile of mirvetuximab soravtansine in this population led the US Food and Drug Administrative (FDA) to grant this agent accelerated approval on November 14, 2022, with regular approval pending review of the confirmatory MIRASOL trial (ClinicalTrials.gov identifier: NCT04209855). The regulatory granting of an accelerated approval by the FDA is dependent on several factors which have been updated in agency documents. In a single-arm study, efficacy is defined by confirmed objective response rate and DOR. The DOR is defined as the time from initial complete or partial response until progressive disease or death, as assessed by the investigator (or blinded independent review) per RECIST v1.1. Time to response is not considered in this metric. The Kaplan-Meier curve for DOR provides the distribution of responses and contextualizes the point estimate of median DOR. To give context to clinical benefit, the agency considers the DOR seen among the fraction of patients achieving objective response from standardized assessment guidelines, such as RECIST v1.1, as well as other factors such as time-dependent end points, including PFS and safety.
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Journal of Clinical Oncology
Too Much, Too Little, or Just Right? Obesity and Dosing of Targeted Therapies in Breast Cancer
Cao C, Ligibel JA
Obesity, a global pandemic, is a well-established prognostic factor in early breast cancer. A recent review from the World Cancer Research Fund including 64 studies evaluating the relationship between obesity and cancer outcomes in early breast cancer found that each 5-kg/m increase in BMI was associated with a concomitant increase in the risk of all-cause mortality, breast cancer–specific mortality, and second cancers. Notably, the poor outcomes associated with obesity have been seen in both pre- and postmenopausal women and across tumor subtypes and treatments.
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Journal of the National Cancer Institute
Disparities in Parental Distress in a Multicenter Clinical Trial for Pediatric Acute Lymphoblastic Leukemia
Umaretiya PJ, Koch VB, Flamand Y, Aziz-Bose R, Ilcisin L, Valenzuela A, Wolfe J, Silverman LB,
Bona K
BACKGROUND: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001.
METHODS: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status.
RESULTS: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1.
CONCLUSIONS: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.
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Nature Communications
Genomic Signatures of Past and Present Chromosomal Instability in Barrett's Esophagus and Early Esophageal Adenocarcinoma
Bao C, Tourdot RW, Brunette GJ, Stewart C, Sun L, Agoston AT, Jajoo K, Getz G, Odze R, Bass AJ, Stachler MD, Zhang CZ
The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we perform haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.
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Nature Genetics
Systematic Profiling of Conditional Pathway Activation Identifies Context-Dependent Synthetic Lethalities
Chang L, Jung NY, Atari A, Rodriguez DJ, Kesar D, Song TY, Rees MG, Ronan M, Li R, Ruiz P, Chaturantabut S, Ito T, van Tienen LM, Tseng YY, Roth JA, Sellers WR
The paradigm of cancer-targeted therapies has focused largely on inhibition of critical pathways in cancer. Conversely, conditional activation of signaling pathways as a new source of selective cancer vulnerabilities has not been deeply characterized. In this study, we sought to systematically identify context-specific gene-activation-induced lethalities in cancer. To this end, we developed a method for gain-of-function genetic perturbations simultaneously across ~500 barcoded cancer cell lines. Using this approach, we queried the pan-cancer vulnerability landscape upon activating ten key pathway nodes, revealing selective activation dependencies of MAPK and PI3K pathways associated with specific biomarkers. Notably, we discovered new pathway hyperactivation dependencies in subsets of APC-mutant colorectal cancers where further activation of the WNT pathway by APC knockdown or direct β-catenin overexpression led to robust antitumor effects in xenograft and patient-derived organoid models. Together, this study reveals a new class of conditional gene-activation dependencies in cancer.
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New England Journal of Medicine
Atezolizumab for Advanced Alveolar Soft Part Sarcoma
Sharon E, Merriam P
Background: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported.
Methods: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action.
Results: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1.
Conclusions: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.).
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Academic Emergency Medicine
The Differences in Code Status Conversation Approaches Reported by Emergency Medicine and Palliative Care Clinicians: A Mixed Method Study
Ouchi K, Prachanukool T, Aaronson EL, Lakin JR, Higuchi M, Liu SW, Kennedy M, Revette AC, Kaithamattam J, Lee B, Hasdianda MA, Schonberg MA, Tulsky JA, Block SD
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Cancer Epidemiology, Biomarkers, and Prevention
Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival
Babic A, Wang QL, Lee AA, Yuan C, Rifai N, Tabung FK, Kim J, Kraft P, Sesso HD, Buring JE, Giovannucci EL, Manson JE, Stampfer MJ, Ng K, Wolpin BM
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Cancer Research
Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer
Hermida-Prado F, Xie Y, Sherman S, Nagy Z, Russo D, Akhshi T, Feit A, Campisi M, Chen M, Nardone A, Guarducci C, Lim K, Font-Tello A, Lee I, Agudo J, Huang Y, Sella T, Jin Q, Tayob N, Mittendorf EA, Tolaney SM, Qiu X, Long H, Lin JR, Santagata S, Richardson ET, Oliveira G, Wu CJ, Barbie D,
Metzger O, Jeselsohn R
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Clinical Cancer Research
A Phase 1 Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-Dose Gemcitabine in Metastatic Pancreatic Adenocarcinoma Patients
Huffman BM, Feng H, Parmar K, Wang J, Kapner KS, Kochupurakkal B, Martignetti DB, Sadatrezaei G, Abrams TA, Biller LH, Giannakis M, Ng K, Patel AK, Perez KJ, Singh H, Rubinson DA, Schlechter BL, Andrews E, Hannigan AM, Dunwell S, Getchell Z, Raghavan S, Wolpin BM, D'Andrea AD, Aguirre AJ, Shapiro GI, Cleary JM
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European Radiology
Advanced Non-Small-Cell Lung Cancer Treated with First-Line Pembrolizumab Plus Chemotherapy: Tumor Response Dynamics as a Marker for Survival
Nishino M, Wang X, Ricciuti B, Tseng SC, Park H, Alessi JV, Vaz VR, Hatabu H, Lin X, Christiani DC, Awad MM
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Hematology/Oncology Clinics of North America
Renal Cell Cancer
McGregor BA, Choueiri TK
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Journal of Palliative Medicine
Top Ten Tips Palliative Care Clinicians Should Know About Delivering Specialty-Aligned Palliative Care
Leiter RE, Gelfand SL, Jain N, Lally K, Landzberg MJ, Lever N, O'Donnell A, Sciacca KR, Snaman JM, Tulsky JA, Lakin JR
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JTO Clinical and Research Reports
Pneumonitis in Patients Receiving Thoracic Radiotherapy and Osimertinib: A Multi-Institutional Study
Banla LI, Tzeng A, Baillieul JP, Kandekhar MJ, Fitzgerald KJ, LoPiccolo J, Poitras HA, Soto DE,
Rotow JK, Willers H, Kozono DE, Janne PA, Mak RH, Piotrowska Z, Keane FK, Kann BH
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Medical Physics
Observer Preference of Artificial Intelligence-Generated Versus Clinical Prostate Contours for Ultrasound-Based High Dose Rate Brachytherapy
King MT, Kehayias CE, Chaunzwa T, Rosen DB, Mahal AR, Wallburn TD, Milligan MG, Dyer MA,
Nguyen PL, Orio PF, Harris TC, Buzurovic I, Guthier CV
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Transplantation and Cellular Therapy
Medication Adherence in Patients with Hematologic Malignancies Who Are Hematopoietic Stem Cell Transplantation Survivors: A Qualitative Study
Amonoo HL, Deary EC, Wang A, Newcomb RA, Daskalakis E, Weber D, Holmbeck KE, Choe JJ,
Nabily A, Cutler C, Traeger LN, El-Jawahri A
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