Welcome to Dana-Farber's Research News
July 1, 2023
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 June 1 through June 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.
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Annals of Oncology
Tarantino P, Bardia A, Burstein HJ, Schnitt SJ, Tolaney SM
HER2-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from 9 different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were: (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the developed statements, including findings from the expert panel discussions, expert opinion and a summary of evidence supporting each statement.
Blood
Merrill MH, Redd RA, McDonough M, Chen YB, DeFilipp Z, Fisher DC, LaCasce AS, Odejide OO,
Ng SY, Jacobson CA, Merryman RW, Kim AI, Armand P, Jacobsen ED
Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for post-transplant maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We therefore conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary endpoint was progression-free survival (PFS) at 18 months post-ASCT. Twenty-one patients were treated on this study and (14) 67% completed 8 cycles of treatment. Among all evaluable patients, 13/21 were alive and progression-free at 18-months post-ASCT, meeting the study's primary endpoint. The estimated 18-month PFS was 83.6% (95% CI: 68 - 100), and OS 94.4% (95% CI: 84 - 100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov (NCT02362997).
Blood
CDK7 Controls E2F- and MYC-Driven Proliferative and Metabolic Vulnerabilities in Multiple Myeloma
Yao Y, Ng JF, Samur M, Morelli E, Chyra Z, Xu Y, Derebail S, Epstein C, Mitsiades C, Anderson KC, Munshi NC, Fulciniti M
Therapeutic targeting of CDK7 has proven beneficial in preclinical studies, yet the off-target effects of currently available CDK7 inhibitors make it difficult to pinpoint the exact mechanisms behind MM cell death mediated by CDK7 inhibition. Here, we show that CDK7 expression positively correlates with E2F and MYC transcriptional programs in cells from patients with multiple myeloma (MM); its selective targeting counteracts E2F activity via perturbation of the cyclin-dependent kinases/Rb axis and impairs MYC-regulated metabolic gene signatures translating into defects in glycolysis and reduced levels of lactate production in MM cells. CDK7 inhibition using the covalent small-molecule inhibitor YKL-5-124 elicits a strong therapeutic response with minimal effects on normal cells, and causes in vivo tumor regression, increasing survival in several mouse models of MM including a genetically engineered mouse model of MYC-dependent MM. Through its role as a critical cofactor and regulator of MYC and E2F activity, CDK7 is therefore a master regulator of oncogenic cellular programs supporting MM growth and survival, and a valuable therapeutic target providing rationale for development of YKL-5-124 for clinical use.
Blood
Five-Year Follow-Up of KEYNOTE-087: Pembrolizumab Monotherapy in Relapsed/Refractory Classical Hodgkin Lymphoma
Armand P, Shipp MA
Previous analyses from the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), but longer-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplant (ASCT) and brentuximab vedotin (BV; cohort 1); after salvage chemotherapy and BV without ASCT (cohort 2); or after ASCT without subsequent BV (cohort 3) received pembrolizumab for ?2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were objective response rate (ORR) by blinded central review and safety. Median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained response ?4 years. Median overall survival was not reached. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 in 12.9%; no treatment-related deaths occurred. Single-agent pembrolizumab can induce very durable responses, especially in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.
Blood
Higher Abatacept Exposure Decreases Acute GVHD Risk Without Increasing Adverse Events
Takahashi T, Bratrude B, Betz KM, Yu A, Neuberg DS, Duncan C, Horan JT, Kean LS
In the "ABA2" study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (AGVHD) after unrelated-donor hematopoietic cell transplantation (URD HCT), leading to FDA approval. Here, we performed a detailed determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response (E-R) relationships impacted key clinical outcomes. To accomplish this, we performed a population PK analysis of intravenous abatacept using nonlinear mixed-effect modeling, and assessed the association between abatacept exposure (dosed at 10 mg/kg on Days -1,+5,+14,+28) and key transplant outcomes. We tested the association between the trough concentration after dose 1 (Ctrough_1) and Grade 2-4 acute GVHD (Gr 2-4 AGVHD) through Day+100 as the primary outcome in 184 HCT patients. An optimal Ctrough_1 threshold was identified by recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a two-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 ?g/mL. However, a higher Ctrough_1 (?39?g/mL, attained in ~60% of ABA2 patients) was associated with a favorable Gr 2-4 AGVHD risk (HR:0.35, 95%CI:0.19-0.65, p<0.001), with a Ctrough_1 <39?g/mL associated with Gr 2-4 AGVHD risk indistinguishable from placebo (p=0.37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, CMV viremia, and EBV viremia. These data demonstrate that, compared to a previously reported target Ctrough_1 of 10 ?g/mL, a higher abatacept Ctrough_1 (?39 ?g/mL) was associated with a favorable Gr 2-4 AGVHD risk, without any observed exposure-toxicity relationships. Clinical trial NCT01743131.
Blood
Improved Survival in cHL with Novel Agents
Merryman RW, LaCasce AS
In this issue of Blood, Spinner et al compare outcomes in patients with relapsed classic Hodgkin lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) in the modern era (2011-2020) with those treated from 2000 to 2010 and find a significant improvement in 4-year overall survival (OS) among patients in the modern era (89.1% vs 79.0%) (see figure). These improved outcomes appear to be driven by an increased use of the novel agents, brentuximab vedotin and PD-1 inhibitors (nivolumab, pembrolizumab), both as part of salvage therapy before ASCT and for relapse after ASCT. In a multivariable analysis, receipt of a PD-1 inhibitor before ASCT was associated with improved OS. In addition, the 4-year OS of patients who developed recurrent disease after ASCT improved from 43.3% to 71.4% in the modern era.
Cancer
Weiss A, Waks AG, Laws A, McGrath M, Tarantino P, Portnow L, Winer E, Partridge AH, Tolaney SM, Mittendorf EA, King TA
BACKGROUND: The optimal treatment strategy for patients with small human epidermal growth factor receptor 2 (HER2)-positive tumors is based on nodal status. The authors' objective was to evaluate pathologic nodal disease (pathologic lymph node-positive [pN-positive] and pathologic lymph node-positive after preoperative systemic therapy [ypN-positive]) rates in patients who had clinical T1-T2 (cT1-cT2)N0M0, HER2-positive breast cancer treated with upfront surgery or neoadjuvant chemotherapy (NAC).
METHODS: Two databases were queried for patients who had cT1-cT2N0M0, HER2-positive breast cancer: (1) the Dana-Farber Brigham Cancer Center (DF/BCC) from February 2015 to October 2020 and (2) the Hospital Clinic of Barcelona and the Hospital Clinico of Valencia (HCB/HCV) from January 2012 to September 2021. The pN-positive/ypN-positive and axillary lymph node dissection (ALND) rates were compared between patients who underwent upfront surgery versus those who received NAC.
RESULTS: Among 579 patients from the DF/BCC database, 368 underwent upfront surgery, and 211 received NAC; the rates of nodal positivity were 19.8% and 12.8%, respectively (p = .021). The pN-positive rates increased by tumor size (p < .001), reaching 25% for those with cT1c tumors. The ypN-positive rates did not correlate with tumor size. NAC was associated with decreased nodal positivity (odds ratio, 0.411; 95% confidence interval, 0.202-0.838), but the ALND rates were similar (22 of 368 patients [6.0%] who underwent upfront surgery vs. 18 of 211 patients [8.5%] who received NAC; p = .173). Among 292 patients from the HCB/HCV database, 119 underwent upfront surgery, and 173 received NAC; the rates of nodal positivity were 21% and 10.4%, respectively (p = .012). The pN-positive rates increased with tumor size (p = .011). The ALND rates were equivalent by treatment strategy (23 of 119 patients [19.3%] who underwent upfront surgery vs. 24 of 173 patients [13.9%] who received NAC; p = .213).
CONCLUSIONS: Among patients who had cT1-cT2N0M0, HER2-positive breast cancer, approximately 20% who underwent upfront surgery were pN-positive, and the rate reached 25% for those with cT1c tumors. Given the opportunity for tailored therapy among lymph node-positive, HER2-positive patients, these data provide rationale for future analyses investigating the utility of routine axillary imaging in patients with HER2-positive breast cancer.
Cancer Discovery
Pancreatic Neoplasms Are Frighteningly Common: A Role for Immune Surveillance?
Hoffman MT, Dougan SK
Carpenter and colleagues analyze organ donors to find that pancreatic intraepithelial neoplasia (PanIN), the precursor lesions of pancreatic ductal adenocarcinoma, are highly prevalent in the average healthy adult starting from a young age. Why these precursor lesions do not progress to cancer in most people is a mystery. See related article by Carpenter et al., p. 1324 (1).
Cancer Discovery
Gunn K, Huang B, Rouaisnel B, Doench JG, Ligon KL, Losman JA
Oncogenic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 occur in a wide range of cancers, including acute myeloid leukemia (AML) and glioma. Mutant IDH enzymes convert 2-oxoglutarate (2OG) to (R)-2-hydroxyglutarate [(R)-2HG], an oncometabolite that is hypothesized to promote cellular transformation by dysregulating 2OG-dependent enzymes. The only (R)-2HG target that has been convincingly shown to contribute to transformation by mutant IDH is the myeloid tumor suppressor TET2. However, there is ample evidence to suggest that (R)-2HG has other functionally relevant targets in IDH-mutant cancers. Here, we show that (R)-2HG inhibits KDM5 histone lysine demethylases and that this inhibition contributes to cellular transformation in IDH-mutant AML and IDH-mutant glioma. These studies provide the first evidence of a functional link between dysregulation of histone lysine methylation and transformation in IDH-mutant cancers.
SIGNIFICANCE: Mutant IDH is known to induce histone hypermethylation. However, it is not known if this hypermethylation is functionally significant or is a bystander effect of (R)-2HG accumulation in IDH-mutant cells. Here, we provide evidence that KDM5 inhibition by (R)-2HG contributes to mutant IDH-mediated transformation in AML and glioma. This article is highlighted in the In This Issue feature, p. 1275.
Journal of Clinical Oncology
At a Loss: Patient Deaths and Clinical Research Coordinators
Deary EC, Daskalakis E, Abrahm JL, Morris SE, Amonoo HL
As clinical research coordinators (CRCs) working on health outcomes research in patients with hematologic malignancies, we frequently navigate a patient's chart to coordinate study appointments and collect clinical information. When opening a patient's electronic health record, a snapshot immediately appears on the screen with the patient's medical information: demographics, problem list, medical history, allergies, medications, and so on. However, there are times when the chart does not open immediately, and our stomachs drop. A small gray pop-up box that we know all too well reads: “You are opening the chart of [patient's name], who is deceased. Date of death: [date].”
Journal of Clinical Oncology
Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer
Wala J, Nguyen P, Pomerantz M
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.For generations, oncologists and urologists have used androgen deprivation therapy (ADT) to manage metastatic hormone-sensitive prostate cancer (mHSPC). Until recently, ADT monotherapy was standard. Within the past decade, a series of trials have clearly demonstrated improved outcomes with a more aggressive up-front approach. Doublet intensification therapy, involving either ADT plus docetaxel or ADT plus any of several second-generation oral androgen-receptor pathway inhibitors (ARPIs), provide considerable survival advantages compared with ADT alone. In 2022, two trials, PEACE-1 and ARASENS, demonstrated the potential of triplet therapy, adding an ARPI to an ADT-docetaxel doublet. In this issue of the journal, Hussain et al provide a post hoc analysis of ARASENS (ADT plus docetaxel, with or without darolutamide), identifying the subpopulations of patients with mHSPC who might benefit most from a triplet regimen. They segment the ARASENS cohort by disease volume and disease risk profile, finding that triplet therapy is associated with improved outcomes regardless of category (although with limited power in the low-volume cohort). Meanwhile, trials are ongoing examining the role of radiotherapy (RT) in mHSPC, a modality previously reserved for localized disease or isolated, symptomatic metastases. Here, we present a mHSPC case and discuss our approach to mHSPC considering recent studies. We recommend triplet therapy for patients who are suitable candidates for chemotherapy, especially for patients with high-volume disease. We also favor aggressive use of RT, when feasible, for patients with low-volume mHSPC.
Journal of Clinical Oncology
Laws A, Punglia RS
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. Patients with high-risk breast lesions (HRLs) or preinvasive breast cancers face an elevated risk of future breast cancer diagnoses. Endocrine therapy in this setting reduces the risk of a future diagnosis but does not confer improved survival, thus the side effects of primary/secondary prevention must be considered relative to the benefits. Here, we discuss the available chemoprevention regimens for patients with HRLs and considerations for selecting a regimen, as well as the decision making surrounding use of adjuvant endocrine therapy for patients with ductal carcinoma in situ (DCIS). For patients with HRLs, available chemoprevention regimens differ by menopausal status, including tamoxifen 20 mg once daily for 5 years and more recently tamoxifen 5 mg once daily for 3 years in both premenopausal and postmenopausal women as well as raloxifene or aromatase inhibitors for postmenopausal women. We recommend a shared decision-making approach with attention to patient preferences related to risk tolerance and side-effect profiles. Low-dose tamoxifen appears to be a particularly favorable choice that is well tolerated, without risk of serious adverse events and offers comparable risk reduction to other regimens. For DCIS, the benefit of endocrine therapy in addition to radiation is small, and appears to be driven mainly by a reduction in contralateral breast diagnoses or new breast cancers. A strategy that reduces the side-effect profile of chemoprevention such as low-dose tamoxifen may be especially appealing in the setting of secondary prevention.
Journal of Clinical Oncology
Youssef G, Rahman R, Bay C, Wang W, Arnaout O, Bi WL, Chang YS, DeSalvo M, Flood TF,
Gerstner ER, Gonzalez Castro LN, Guenette JP, Kim AE, Lee EQ, McFaline-Figueroa JR, Potter CA, Reardon DA, Huang RY, Wen PY
PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria are widely used in high-grade glioma clinical trials. We compared the RANO criteria with updated modifications (modified RANO [mRANO] and immunotherapy RANO [iRANO] criteria) in patients with newly diagnosed glioblastoma (nGBM) and recurrent GBM (rGBM) to evaluate the performance of each set of criteria and inform the development of the planned RANO 2.0 update.
MATERIALS AND METHODS: Evaluation of tumor measurements and fluid-attenuated inversion recovery (FLAIR) sequences were performed by blinded readers to determine disease progression using RANO, mRANO, iRANO, and other response assessment criteria. Spearman's correlations between progression-free survival (PFS) and overall survival (OS) were calculated.
RESULTS: Five hundred twenty-six nGBM and 580 rGBM cases were included. Spearman's correlations were similar between RANO and mRANO (0.69 [95% CI, 0.62 to 0.75] v 0.67 [95% CI, 0.60 to 0.73]) in nGBM and rGBM (0.48 [95% CI, 0.40 to 0.55] v 0.50 [95% CI, 0.42 to 0.57]). In nGBM, requirement of a confirmation scan within 12 weeks of completion of radiotherapy to determine progression was associated with improved correlations. Use of the postradiation magnetic resonance imaging (MRI) as baseline scan was associated with improved correlation compared with use of the pre-radiation MRI (0.67 [95% CI, 0.60 to 0.73] v 0.53 [95% CI, 0.42 to 0.62]). Evaluation of FLAIR sequences did not improve the correlation. Among patients who received immunotherapy, Spearman's correlations were similar among RANO, mRANO, and iRANO.
CONCLUSION: RANO and mRANO demonstrated similar correlations between PFS and OS. Confirmation scans were only beneficial in nGBM within 12 weeks of completion of radiotherapy, and there was a trend in favor of the use of postradiation MRI as the baseline scan in nGBM. Evaluation of FLAIR can be omitted. The iRANO criteria did not add significant benefit in patients who received immune checkpoint inhibitors.
Journal of Clinical Oncology
Quality Surgical Care and Outcomes for Patients With Non-Small-Cell Lung Cancer
Kehl KL, Jaklitsch MT
The curative potential of surgical resection for non–small-cell lung cancer (NSCLC) was established nearly a century ago, with pneumonectomy initially constituting the primary operative approach. As surgical techniques became more refined, lobectomy when feasible became the standard of care and less invasive techniques including video-assisted thoracic surgery and robotic-assisted thoracoscopic surgery have reduced surgical morbidity. Despite the evolving role of systemic therapy in the treatment of early-stage NSCLC, now including cytotoxic chemotherapy, targeted therapy, and immunotherapy, surgical resection still plays a critical role in curative treatment.
Journal of Clinical Oncology
D'Amico AV
We thank Mai et al for giving us the opportunity to provide clarification on our recently published article. We agree that the preradical prostatectomy prostate-specific antigen (PSA) level (>20, 10-20, v 4-10 ng/mL [reference]), prostatectomy Gleason score (8-10, 7 v 6 [reference]), tumor category (T3b/4, T3a v T2 [reference]), and margin status (positive v negative [reference]) are all important predictors of both prostate cancer-specific and all-cause mortalities (PCSM, ACM). We mention in the statistical methods section that the model was adjusted for known prostate cancer prognostic factors, which included these factors. These adjustments were made to account for any differences that may exist between treatment groups as noted in Table 1 (Distribution of patient characteristics stratified by treatment). We did perform the same analyses evaluating for the end point of PCSM as mentioned in the results section. We found a very similar adjusted hazard ratio for PCSM as we did for ACM when comparing treatment initiating salvage radiation therapy at a PSA level of >0.25 ng/mL with 0.25 ng/mL or less. Specifically, these respective adjusted hazard ratios and 95% CIs were 1.43 (95% CI, 0.80 to 2.55) and 1.49 (95% CI, 1.11 to 2.00), but given a smaller number of prostate cancer as compared with all-cause deaths being 109 versus 1,269, respectively, the 95% CI for the adjusted hazard ratio for PCSM included 1.0. However, ACM is the most robust end point given that it is not subject to the potential for misclassification or ascertainment bias, which can exist when specifying a specific cause of death.
Journal of Clinical Oncology
Bender HG, Kao PC, London WB
PURPOSE: In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.
PATIENTS AND METHODS: Children
RESULTS: For 12-18mo/Stage4/FavBiology, 5-year EFS/OS (± SE) before (?2006; n = 40) versus after (>2006; n = 55) assigned reduction in therapy was similar: 89% ± 5.1%/89% ± 5.1% versus 87% ± 4.6%/94% ± 3.2% (P = .7; P = .4, respectively). For 12-18mo/Stage3/MYCN-NA/Unfav, the 5-year EFS and OS were both 100%, before (n = 6) and after (n = 4) 2006. The 12- 18mo/Stage4/FavBiology plus 12-18mo/Stage3/MYCN-NA/Unfav classified as high-risk ?2006 had an EFS/OS of 91% ± 4.4%/91% ± 4.5% versus 38% ± 1.3%/43% ± 1.3% for all other high-risk patients2006 had an EFS/OS of 88% ± 4.3%/95% ± 2.9% versus 88% ± 0.9%/95% ± 0.6% for all other intermediate-risk patients
CONCLUSION: Excellent outcome was maintained among subsets of toddlers with neuroblastoma assigned to reduced treatment after reclassification of risk group from high to intermediate on the basis of new age cutoffs. Importantly, as documented in prior trials, intermediate-risk therapy is not associated with the degree of acute toxicity and late effects commonly observed with high-risk regimens.
Journal of the National Cancer Institute
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 ages 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 ?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.
CONCLUSION: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared to unexposed parents-experienced 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.
JAMA Oncology
Assessment and Prognostic Value of Inflammatory Biomarkers in Patients with Colon Cancer - Reply
Meyerhardt JA
In Reply We thank McGovern et al for their interest in our analysis of inflammatory biomarkers and survival among patients with stage III colon cancer (CALGB/SWOG 80702).1 In this cohort study, we reported the levels of plasma inflammatory biomarkers, including interleukin 6 (IL-6), soluble tumor necrosis factor ? receptor 2 (sTNF-?R2), and high-sensitivity C-reactive protein (CRP). We found that higher inflammation after diagnosis was significantly associated with worse survival among patients with stage III colon cancer.
JAMA Oncology
Waks AG, Ogayo ER, Tarantino P, Desai N, Guerriero J, Metzger O, Tung NM, Krop IE, Winer EP, Tolaney SM, Mittendorf EA
IMPORTANCE: Patients with early-stage ERBB2 (formerly HER2)-positive breast cancer (ERBB2+ BC) who experience a pathologic complete response (pCR) after receiving neoadjuvant therapy have favorable survival outcomes. Predicting the likelihood of pCR may help optimize neoadjuvant therapy.
OBJECTIVE: To test the ability of the HER2DX assay to predict the likelihood of pCR in patients with early-stage ERBB2+ BC who are receiving deescalated neoadjuvant therapy.
DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic/prognostic study, the HER2DX assay was administered on pretreatment tumor biopsy samples from patients enrolled in the single-arm, multicenter, prospective phase 2 DAPHNe clinical trial who had newly diagnosed stage II to III ERBB2+ BC that was treated with neoadjuvant paclitaxel weekly for 12 weeks plus trastuzumab and pertuzumab every 3 weeks for 4 cycles.
INTERVENTIONS AND EXPOSURES: The HER2DX assay is a classifier derived from gene expression and limited clinical features that provides 2 independent scores to predict prognosis and likelihood of pCR in patients with early-stage ERBB2+ BC. The assay was administered on baseline tumor samples from 80 of 97 patients (82.5%) in the DAPHNe trial.
MAIN OUTCOMES AND MEASURES: The primary aim was to test the ability of the HER2DX pCR likelihood score (as a continuous variable from 0-100) to predict pCR (ypT0/isN0).
RESULTS: Of 80 participants, 79 (98.8%) were women and there were 4 African American (5.0%), 6 Asian (7.5%), 4 Hispanic (5.0%), and 66 White individuals (82.5%); the mean (range) age was 50.3 (26.0-78.0) years. The HER2DX pCR score was significantly associated with pCR (odds ratio, 1.05; 95% CI, 1.03-1.08; P?
CONCLUSIONS AND RELEVANCE: The results of this diagnostic/prognostic study suggest that the HER2DX pCR score assay could predict pCR following treatment with deescalated neoadjuvant paclitaxel with trastuzumab and pertuzumab in patients with early-stage ERBB2+ BC. The HER2DX pCR score might guide therapeutic decisions by identifying patients who are candidates for deescalated or escalated approaches.
JAMA Oncology
Diagnosis and Management of Tropomyosin Receptor Kinase Fusion-Positive Thyroid Carcinomas: A Review
Haddad R, Sadow PM
IMPORTANCE: Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions.
OBSERVATIONS: The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy.
CONCLUSIONS AND RELEVANCE: This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.
JAMA Oncology
Haddad R
IMPORTANCE: There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
OBJECTIVE: To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN.
DESIGN, SETTING, AND PARTICIPANTS: The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock).
INTERVENTIONS: Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal.
MAIN OUTCOMES AND MEASURES: The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety.
RESULTS: Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n?=?159; nivolumab, n?=?82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n?=?123; nivolumab, n?=?61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P?=?.29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease.
CONCLUSIONS AND RELEVANCE: The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.
JAMA Oncology
Is Appendiceal Cancer a Lynch Syndrome-Associated Cancer?
Yurgelun MB, Papke DJ Jr, Redston MS
To the Editor We read with interest the cohort study by Holowatyj et al1 examining the prevalence and spectrum of cancer susceptibility gene pathogenic germline variants (PGVs) among individuals with appendiceal cancer referred for germline testing. We want to congratulate the authors on their study, especially since appendiceal cancers have historically been understudied. As has now become common in the genetic testing literature,2 probands were ascertained from a genetic testing laboratory,1 suggesting elevated pretest suspicion for inherited cancer risk, so the findings are not generalizable to all patients with appendiceal cancer.
Lancet
Choueiri TK
BACKGROUND: Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment.
METHODS: CONTACT-03 was a multicentre, randomised, open-label, phase 3 trial, done in 135 study sites in 15 countries in Asia, Europe, North America, and South America. Patients aged 18 years or older with locally advanced or metastatic renal cell carcinoma whose disease had progressed with immune checkpoint inhibitors were randomly assigned (1:1) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus cabozantinib (60 mg orally once daily) or cabozantinib alone. Randomisation was done through an interactive voice-response or web-response system in permuted blocks (block size four) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk group, line of previous immune checkpoint inhibitor therapy, and renal cell carcinoma histology. The two primary endpoints were progression-free survival per blinded independent central review and overall survival. The primary endpoints were assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT04338269, and is closed to further accrual.
FINDINGS: From July 28, 2020, to Dec 27, 2021, 692 patients were screened for eligibility, 522 of whom were assigned to receive atezolizumab-cabozantinib (263 patients) or cabozantinib (259 patients). 401 (77%) patients were male and 121 (23%) patients were female. At data cutoff (Jan 3, 2023), median follow-up was 15·2 months (IQR 10·7-19·3). 171 (65%) patients receiving atezolizumab-cabozantinib and 166 (64%) patients receiving cabozantinib had disease progression per central review or died. Median progression-free survival was 10·6 months (95% CI 9·8-12·3) with atezolizumab-cabozantinib and 10·8 months (10·0-12·5) with cabozantinib (hazard ratio [HR] for disease progression or death 1·03 [95% CI 0·83-1·28]; p=0·78). 89 (34%) patients in the atezolizumab-cabozantinib group and 87 (34%) in the cabozantinib group died. Median overall survival was 25·7 months (95% CI 21·5-not evaluable) with atezolizumab-cabozantinib and was not evaluable (21·1-not evaluable) with cabozantinib (HR for death 0·94 [95% CI 0·70-1·27]; p=0·69). Serious adverse events occurred in 126 (48%) of 262 patients treated with atezolizumab-cabozantinib and 84 (33%) of 256 patients treated with cabozantinib; adverse events leading to death occurred in 17 (6%) patients in the atezolizumab-cabozantinib group and nine (4%) in the cabozantinib group.
INTERPRETATION: The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials.
FUNDING: F Hoffmann-La Roche and Exelixis.
Lancet Oncology
Dieffenbach BV, Diller LR, Weil BR, Weldon CB
BACKGROUND: Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions.
METHODS: We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in the USA, with a comparison group of nearest-age siblings of survivors selected by simple random sampling. The primary outcome was any self-reported late, major surgical intervention (defined as any anaesthesia-requiring operation) occurring 5 years or more after the primary cancer diagnosis. The cumulative burden was assessed with mean cumulative counts (MCC) of late, major surgical interventions. Piecewise exponential regression models with calculation of adjusted rate ratios (RRs) evaluated associations between treatment exposures and late, major surgical interventions.
FINDINGS: Between Jan 1, 1970, and Dec 31, 1999, 25?656 survivors were diagnosed (13?721 male, 11?935 female; median follow-up 21·8 years [IQR 16·5-28·4]; median age at diagnosis 6·1 years [3·0-12·4]); 5045 nearest-age siblings were also included as a comparison group. Survivors underwent 28?202 late, major surgical interventions and siblings underwent 4110 late, major surgical interventions. The 35-year MCC of a late, major surgical intervention was 206·7 per 100 survivors (95% CI 202·7-210·8) and 128·9 per 100 siblings (123·0-134·7). The likelihood of a late, major surgical intervention was higher in survivors versus siblings (adjusted RR 1·8, 95% CI 1·7-1·9) and in female versus male survivors (1·4; 1·4-1·5). Survivors diagnosed in the 1990s (adjusted RR 1·4, 95% CI 1·3-1·5) had an increased likelihood of late surgery compared with those diagnosed in the 1970s. Survivors received late interventions more frequently than siblings in most anatomical regions or organ systems, including CNS (adjusted RR 16·9, 95% CI 9·4-30·4), endocrine (6·7, 5·2-8·7), cardiovascular (6·6, 5·2-8·3), respiratory (5·3, 3·4-8·2), spine (2·4, 1·8-3·2), breast (2·1, 1·7-2·6), renal or urinary (2·0, 1·5-2·6), musculoskeletal (1·5, 1·4-1·7), gastrointestinal (1·4, 1·3-1·6), and head and neck (1·2, 1·1-1·4) interventions. Survivors of Hodgkin lymphoma (35-year MCC 333·3 [95% CI 320·1-346·6] per 100 survivors), Ewing sarcoma (322·9 [294·5-351·3] per 100 survivors), and osteosarcoma (269·6 [250·1-289·2] per 100 survivors) had the highest cumulative burdens of late, major surgical interventions. Locoregional surgery or radiotherapy cancer treatment were associated with undergoing late surgical intervention in the same body region or organ system.
INTERPRETATION: Childhood cancer survivors have a significant burden of late, major surgical interventions, a late effect that has previously been poorly quantified. Survivors would benefit from regular health-care evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible.
FUNDING: US National Institutes of Health, US National Cancer Institute, American Lebanese Syrian Associated Charities, and St Jude Children's Research Hospital.
Molecular Cell
Irisin Acts Through its Integrin Receptor in a Two-Step Process Involving Extracellular Hsp90?
A M, Zhou H, Gorgulla C, Blackmore KA, Mittenbühler MJ, Kim CR, Bogoslavski D, Zhang Q,
Wang ZF, Jedrychowski MP, Seo HS, Song K, Xu AZ, Sebastian L, Gygi SP, Arthanari H,
Dhe-Paganon S, Spiegelman BM
Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via ?V integrins; however, a mechanistic understanding of how small polypeptides like irisin can signal through integrins is poorly understood. Using mass spectrometry and cryo-EM, we demonstrate that the extracellular heat shock protein 90? (eHsp90?) is secreted by muscle with exercise and activates integrin ?V?5. This allows for high-affinity irisin binding and signaling through an Hsp90?/?V/?5 complex. By including hydrogen/deuterium exchange data, we generate and experimentally validate a 2.98 Å RMSD irisin/?V?5 complex docking model. Irisin binds very tightly to an alternative interface on ?V?5 distinct from that used by known ligands. These data elucidate a non-canonical mechanism by which a small polypeptide hormone like irisin can function through an integrin receptor.
Nature
Heritable Transcriptional Defects from Aberrations of Nuclear Architecture
Papathanasiou S, Mynhier NA, Liu S, Brunette G, Stokasimov E, Jacob E, Li L, Comenho C, Buenrostro JD, Zhang CZ, Pellman D
Transcriptional heterogeneity due to plasticity of the epigenetic state of chromatin contributes to tumour evolution, metastasis and drug resistance1-3. However, the mechanisms that cause this epigenetic variation are incompletely understood. Here we identify micronuclei and chromosome bridges, aberrations in the nucleus common in cancer4,5, as sources of heritable transcriptional suppression. Using a combination of approaches, including long-term live-cell imaging and same-cell single-cell RNA sequencing (Look-Seq2), we identified reductions in gene expression in chromosomes from micronuclei. With heterogeneous penetrance, these changes in gene expression can be heritable even after the chromosome from the micronucleus has been re-incorporated into a normal daughter cell nucleus. Concomitantly, micronuclear chromosomes acquire aberrant epigenetic chromatin marks. These defects may persist as variably reduced chromatin accessibility and reduced gene expression after clonal expansion from single cells. Persistent transcriptional repression is strongly associated with, and may be explained by, markedly long-lived DNA damage. Epigenetic alterations in transcription may therefore be inherently coupled to chromosomal instability and aberrations in nuclear architecture.
Nature
Ultraviolet Radiation Shapes Dendritic Cell Leukaemia Transformation in the Skin
Griffin GK, Booth CAG, Togami K, Chung SS, Ssozi D, Verga JA, Bouyssou JM, Lee YS,
Shanmugam V, Hornick JL, LeBoeuf NR, Morgan EA, Bernstein BE, Hovestadt V, van Galen P,
Lane AA
Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute to disease pathology in peripheral tissues1-4. Outside the marrow, these clones are potentially exposed to a variety of tissue-specific mutational processes, although the consequences of this are unclear. Here we investigate the development of blastic plasmacytoid dendritic cell neoplasm (BPDCN)-an unusual form of acute leukaemia that often presents with malignant cells isolated to the skin5. Using tumour phylogenomics and single-cell transcriptomics with genotyping, we find that BPDCN arises from clonal (premalignant) haematopoietic precursors in the bone marrow. We observe that BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet (UV) radiation. A reconstruction of tumour phylogenies reveals that UV damage can precede the acquisition of alterations associated with malignant transformation, implicating sun exposure of plasmacytoid dendritic cells or committed precursors during BPDCN pathogenesis. Functionally, we find that loss-of-function mutations in Tet2, the most common premalignant alteration in BPDCN, confer resistance to UV-induced cell death in plasmacytoid, but not conventional, dendritic cells, suggesting a context-dependent tumour-suppressive role for TET2. These findings demonstrate how tissue-specific environmental exposures at distant anatomical sites can shape the evolution of premalignant clones to disseminated cancer.
Nature Cancer
de Matos Simoes R, Shirasaki R, Downey-Kopyscinski SL, Matthews GM, Yamano S, Hu Y, Sheffer M, Dhimolea E, Dashevsky O, Gandolfi S, Ishiguro K, Meyers RM, Bryan JG, Dharia NV, Hengeveld PJ, Brüggenthies JB, Tang H, Aguirre AJ, Sievers QL, Ebert BL, Glassner BJ, Ott CJ, Bradner JE, Kwiatkowski NP, Groen RWJ, Gray NS, Culhane AC, McFarland JM, Dempster JM, Hahn WC, Vazquez F, Tsherniak A, Mitsiades CS
Clinical progress in multiple myeloma (MM), an incurable plasma cell (PC) neoplasia, has been driven by therapies that have limited applications beyond MM/PC neoplasias and do not target specific oncogenic mutations in MM. Instead, these agents target pathways critical for PC biology yet largely dispensable for malignant or normal cells of most other lineages. Here we systematically characterized the lineage-preferential molecular dependencies of MM through genome-scale clustered regularly interspaced short palindromic repeats (CRISPR) studies in 19 MM versus hundreds of non-MM lines and identified 116 genes whose disruption more significantly affects MM cell fitness compared with other malignancies. These genes, some known, others not previously linked to MM, encode transcription factors, chromatin modifiers, endoplasmic reticulum components, metabolic regulators or signaling molecules. Most of these genes are not among the top amplified, overexpressed or mutated in MM. Functional genomics approaches thus define new therapeutic targets in MM not readily identifiable by standard genomic, transcriptional or epigenetic profiling analyses.
Nature Communications
Identification of BRCA1/2 Mutation Female Carriers Using Circulating MicroRNA Profiles
Elias K, Webber J, Kaplan J, Garber JE, Konstantinopoulos P, Fendler W, Chowdhury D
Identifying germline BRCA1/2 mutation carriers is vital for reducing their risk of breast and ovarian cancer. To derive a serum miRNA-based diagnostic test we used samples from 653 healthy women from six international cohorts, including 350 (53.6%) with BRCA1/2 mutations and 303 (46.4%) BRCA1/2 wild-type. All individuals were cancer-free before and at least 12 months after sampling. RNA-sequencing followed by differential expression analysis identified 19 miRNAs significantly associated with BRCA mutations, 10 of which were ultimately used for classification: hsa-miR-20b-5p, hsa-miR-19b-3p, hsa-let-7b-5p, hsa-miR-320b, hsa-miR-139-3p, hsa-miR-30d-5p, hsa-miR-17-5p, hsa-miR-182-5p, hsa-miR-421, hsa-miR-375-3p. The final logistic regression model achieved area under the receiver operating characteristic curve 0.89 (95% CI: 0.87-0.93), 93.88% sensitivity and 80.72% specificity in an independent validation cohort. Mutated gene, menopausal status or having preemptive oophorectomy did not affect classification performance. Circulating microRNAs may be used to identify BRCA1/2 mutations in patients of high risk of cancer, offering an opportunity to reduce screening costs.
Advanced Healthcare Materials
New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay
Wan Z, Shelton SE, Barbie DA
Biochimica et Biophysica Acta Gene Regulatory Mechanisms
Proteomic Approaches to Study Ubiquitinomics
Sahu I, Zhu H, Buhrlage SJ, Marto JA
Blood Advances
Gooptu M, Kim HT, Jacobsen E, Fisher DC, LaCasce A, Ho VT, Cutler CS, Koreth J, Soiffer RJ,
Antin JH, Berliner N, Nikiforow S
Blood Advances
Genomics of PDGFR-Rearranged Hypereosinophilic Syndrome
Rheinbay E, Qi M, Bouyssou JM, Lane AA
Blood Advances
Maurer K, Kim HT, Garrity HM, Liney D, Cutler C, Antin JH, Koreth J, Ritz J, Shapiro RM, Romee R, Ho VT, Gooptu M, Soiffer RJ, Wu CJ, Nikiforow S
British Journal of Haematology
Dose Reductions in Patients with Waldenström Macroglobulinaemia Treated with Ibrutinib
Sarosiek S, Gustine JN, Flynn CA, Leventoff C, Little M, White T, Meid K, Treon SP, Castillo JJ
Cancer Immunology, Immunotherapy
Silk AW, Kaufman HL
Cancer Immunology Research
Saliby RM, El Zarif T, Bakouny Z, Shah V, Xie W, Denize T, Ficial M, Hirsch L, Wei XX, Steinarter JA, Harshman LC, Severgnini M, McDermott DF, Lee GM, Xu W, Van Allen EM, McGregor BA,
Signoretti S, Choueiri TK
Cancer Immunology Research
Li X, Li J, Zheng Y, Lee SJ, Zhou J, Giobbie-Hurder A, Hodi FS
Cancer Medicine
Shaikh R, Weil BR, Weldon CB, Chen N, London WB, Krush M, Anderson M, Gebhardt M, Church AJ, DuBois SG, Pikman Y, Spidle J, Wall CB, Feraco A, Ullrich NJ, Mack JW, Mullen E, Kamihara J, Forrest S, Shusterman S, Janeway KA, Alomari A, Padua H, O'Neill AF
Cancer Medicine
Phase 2 Trial of palbociclib and Ganitumab in Patients with Relapsed Ewing Sarcoma
Shulman DS, Merriam P, Choy E, Cavanaugh KL, Kao PC, Posner A, Bhushan K, Fairchild G,
Barker E, Klega K, Stegmaier K, Crompton BD, London WB, DuBois SG
Clinical Cancer Research
Accessible Data Collections for Improved Decision Making in Neuro-Oncology Clinical Trials
Rahman R, Redd R, Alexander BM, Wen PY, Trippa L
Clinical Cancer Research
Paweletz CP, Heavey GA, Kuang Y, Durlacher E, Janne PA
Clinical Cancer Research
Keeping t in the Family: HER3 as a Target in Brain Metastases
Lin NU
Cancer Prevention Research
Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ
Garber JE, Husband A, Pastorello R, Mittendorf EA
Clinical Cancer Research
Wang QL, Ma C, Yuan C, Wolpin BM, Zhang Y, Meyerhardt JA, Ng K
Current Treatment Options in Oncology
Available Systemic Treatments and Emerging Therapies for Breast Cancer Brain Metastases
Lin NU, Sammons SL
Current Treatment Options in Oncology
Brett JO, Mayer EL
European Urology Oncology
D'Amico AV
Haematologica
Crombie JL, Jacobson CA, Redd R, Saucier A, Armand P
Haematologica
The International Prognostic Index: Still Relevant 30 Years Later
LaCasce AS
Hematology/Oncology Clinics of North America
Insights into Renal Cell Carcinoma with Novel Imaging Approaches
Schawkat K, Krajewski KM
Hematology/Oncology Clinics of North America
Targeted Therapy for Non-Small Cell Lung Cancer: First Line and Beyond
Brea E, Rotow J
Hematology/Oncology Clinics of North America
von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology
Shirole NH, Kaelin WG Jr
JAMA Internal Medicine
Private Equity Acquisition of Oncology Clinics in the US From 2003 to 2022
Tyan K, Lam MB, Milligan M
JAMA Pediatrics
Goals of Care Among Parents of Children Receiving Palliative Care
Wolfe J
JCO Oncology Practice
Lynch DM, Menon S, Mazzola E, Costa J, Jabaley T
JCO Oncology Practice
Stockman LS, Gundersen DA, Gikandi A, Akindele RN, Svoboda L, Pohl S, Lathan CS
JCO Oncology Practice
Roberts DA, Faig J, Wischhusen J, Giordano S, Acharya U, Drews R, Dougherty D, Lathan C, Rangachari D
Journal of the American Academy of Dermatology
Zhong CS, Horiguchi M, Uno H, Ukaegbu C, Chittenden A, LeBoeuf NR, Syngal S, Nambudiri VE, Yurgelun MB
Journal of the American Academy of Dermatology
Singer S, Tan SY, Davids M, LaCasce AS, Treon SP, LeBoeuf NR
Journal of the American Academy of Dermatology
Jfri A, Virgen CA, Tawa M, Giobbie-Hurder A, Kupper TS, Fisher DC, LeBoeuf NR, Larocca C
Journal of Correctional Health Care
Cancer Screening Rates and Outcomes for Justice-Involved Individuals: A Scoping Review
Manz CR, Odayar VS
Journal of Immunotherapy
Buchbinder EI, Pfaff KL, Turner MM, Manos M, Ouyang O, Ott PA, Giobbie-Hurder A, Rodig SJ,
Hodi FS
Journal of Music Therapy
Knoerl R, Mazzola E, Woods H, Buchbinder E, Frazier L, LaCasce A, Luskin MR, Phillips CS, Ligibel J
Journal of Nuclear Medicine Technology
Liu M, Cheng SC, Abbott A, Dubey S, Van den Abbeele AD, Overmoyer B, Jacene H
Journal of Pain and Symptom Management
Patient-Reported Outcome Benefits for Children with Advanced Cancer and Parents: A Qualitative Study
Merz A, Feifer D, Avery M, Tsuchiyose E, Eche I, Awofeso O, Wolfe J, Dussel V, Requena ML
Journal of Pain and Symptom Management
Shared Decision Making in the Geriatric Surgery Verification Program: Assessing Baseline Performance
Streid JL, Lee KC, Bader AM, Jarman MP, Cooper Z, Lindvall C
Journal of Thoracic Oncology
Letter to the Editor: Reply to Zhao, Wu, and Ma
Alessi JV, Ricciuti B, Awad MM
Lancet Haematology
Tramontano AC, LaCasce AS, Roemer L, Abel GA, Odejide OO
Leukemia Research
Munshi NC
Molecular Cancer Research
Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers
Venkadakrishnan VB, Yamada Y, Weng K, Idahor O, Beltran H
Nature Reviews Clinical Oncology
Optimizing the Safety of Antibody-Drug Conjugates for Patients with Solid Tumours
Tarantino P, Ricciuti B, Tolaney SM
Neuro-Oncology
A Genomic Score to Predict Local Control among Patients with Brain Metastases Managed with Radiation
Lamba N, Catalano PJ, Kim D, Elhalawani H, Haas-Kogan DA, Wen PY, Wagle N, Aizer AA
Neuro-Oncology
Phase I Study of a Novel Glioblastoma Radiation Therapy Schedule Exploiting Cell-State Plasticity
Dean JA, Tanguturi SK, Cagney D, Shin KY, Youssef G, Aizer A, Rahman R, Hammoudeh L,
Reardon D, Lee E, Dietrich J, Wickersham L, Wen PY, Catalano P, Haas-Kogan D, Alexander BM, Michor F
Neuro-Oncology Practice
The Predictive Value of Partial MGMT Promoter Methylation for IDH-Wild-Type Glioblastoma Patients
Torre M, Wen PY, Iorgulescu JB
NPJ Breast Cancer
Clinical Outcomes of De Novo Metastatic HER2-Positive Inflammatory Breast Cancer
Garrido-Castro AC, Regan MM, Niman SM, Nakhlis F, Remolano C, Rosenbluth JM, Block C,
Warren LE, Bellon JR, Yeh E, Harrison BT, Troll E, Lin NU, Tolaney SM, Overmoyer B, Lynce F
NPJ Precision Oncology
Zhao M, Lau MC, Haruki K, Väyrynen JP, Gurjao C, Väyrynen SA, Dias Costa A, Borowsky J, Fujiyoshi K, Arima K, Hamada T, Lennerz JK, Nishihara R, Chan AT, Ng K, Zhang X, Meyerhardt JA, Song M, Wang M, Giannakis M, Nowak JA, Yu KH, Ugai T, Ogino S
Oncologist
Virgen CA, Sparks JA, Nohria A, O'Hare MJ, Said JT, Tawa M, LeBoeuf NR, Kupper TS, Fisher DC, Larocca C
Oncologist
Molecular Advances in the Treatment of Advanced Gastrointestinal Stromal Tumor
Venkataraman V, George S, Cote GM
Pediatric Blood and Cancer
Valenzuela A, Hawkins A, Revette A, Chen L, Xiong N, Mazzola E, Eche IJ, Snaman JM, Wolfe J,
Bona K, Umaretiya PJ
Psycho-Oncology
Recklitis CJ, Michaud A, Blackmon JE, Chang G
Radiotherapy and Oncology
Nowicka Z, Stawiski K, Ussowicz M
Telemedicine and e-Health
Onyeaka HK, Deary EC, Amonoo HL
Translational Oncology
Bakouny Z, Labaki C, Choueiri TK, Morgans A, Nohria A
Transplantation and Cellular Therapy
Aleissa MM, Little JS, Davey S, Saucier A, Zhou G, Gonzalez-Bocco IH, Crombie JL, Looka A,
Baden LR, Issa NC, Hammond SP, Jacobson CA, Sherman AC
Trends in Microbiology
Viral Sponges Sequester Nucleotide Signals to Inactivate Immunity
Richmond-Buccola D, Kranzusch PJ